The National Institute of Diabetes & Digestive & Kidney Diseases

Ancillary Studies to NIDDK Major Ongoing Clinical Research Studies

Below is a list of NIDDK-sponsored, ongoing clinical research studies that are eligible for ancillary study grant applications under PAR (NIH Guide). Please note that the ancillary study policies for some studies are currently under development. As policies become available, they will be posted on this website under the appropriate study.

For studies related to Digestive Diseases contact Barbara Harrison at (301) 594-8858 or by e-mail at bh72k@nih.gov

• Biliary Atresia Research Consortium (BARC): Nine pediatric liver disease centers and a central data coordinating center make up the consortium, whose central aims are to develop and test hypotheses on the etiology of biliary atresia and to help define the optimal means of diagnosis and management of this disease. Included in this consortium are both retrospective and prospective studies of children with biliary atresia and a similar number of control children with other neonatal liver diseases. The BARC group also has developed a prospective, randomized placebo-controlled trial on the use of high-dose corticosteroids at the time of the Kasai operation, focusing upon whether this therapy promotes increased bile flow and improves outcomes. Serum, urine, peripheral blood lymphocytes, genomic DNA, and liver and biliary tree samples are collected in this consortium. The study has a well-defined ancillary study policy and a process for submission of ancillary studies to be approved by the Ancillary Studies Committee. The policy and online proposal submission site may be found at  www.med.umich.edu/borc/barc/index.htm 
  
  
• Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL): This study supports nine liver transplant centers with expertise in adult living-donor liver transplantation (LDLT) and a central data coordinating center. The major aims of A2ALL are as follows:
  
  
  • Quantify the impact of choosing LDLT on the candidate for transplantation
  • Characterize the difference between LDLT and deceased donor liver transplant (DDLT) in terms of post-transplant outcomes, including patient and graft survival, surgical morbidity, and resource utilization on the recipient of a transplant
  • Determine the short- and long-term health and quality of life (QOL) impact of donation, including (a) morbidity after liver donation and (b) long-term health-related QOL of donors compared to a control population
  • Standardize and assess the role of "informed consent" in affecting the decision to donate and satisfaction after living liver donation
  • Other aims include comparison of the severity of recurrence of hepatocellular carcinoma for DDLT versus LDLT, the systematic characterization of liver regeneration and function in donors and recipients, the evaluation of the differences in the immune response to LDLT versus DDLT, and the establishment of a robust data and sample repository on liver transplantation that may be used to study clinical and biological questions as new technologies and resources become available. Patients enrolled in the study will be followed and managed in a standardized fashion. Serum, peripheral blood lymphocytes, genomic DNA, and liver biopsy material will be collected and stored in a central repository. The A2ALL study group has developed a policy on ancillary studies, which is available at their website: www.nih-a2all.org.
    
    
• Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN): Constituted to help define the etiology, contributing factors, natural history, complications, and therapy of nonalcoholic fatty liver disease, the network includes eight clinical centers and a data coordinating center. Approximately 1,500 pediatric and adult participants with nonalcoholic liver disease will be included in both retrospective and prospective databases beginning in late 2003. Serum, liver tissue, and genomic DNA samples will be collected and stored in a central repository for ongoing as well as future studies. A three-arm randomized, placebo-controlled clinical trial of an insulin-sensitizing agent or vitamin E has been designed, which will be conducted in 240 non-diabetic adult participants with documented NASH. A separate trial in pediatric NASH patients will randomize 180 children to receive treatment with vitamin E, metformin, or placebo. All patients in both clinical trials will have liver biopsies taken before and at the end of the two years of treatment. Enrollment into both trials will begin in early 2004. The NASH CRN will be open to review and approval of ancillary studies of merit that involve limited additional burden to study participants. The ancillary study policy is posted on the NASH CRN website:  www.nashcrn.com.
  
  
• Peginterferon and Ribavirin for Pediatric Patients with Chronic Hepatitis C (Peds-C): This prospective, randomized controlled trial will study peginterferon therapy, with or without ribavirin, in children with chronic hepatitis C. The trial is being conducted by eleven clinical centers and a central coordinating center. Approximately 120 children will be randomly assigned to receive peginterferon alfa-2a alone or peginterferon with ribavirin for 48 weeks. Children will be carefully monitored for serum markers of liver disease and hepatitis C virus levels as well as side effects of therapy, growth and development, and quality of life. A long-term follow up study of the clinical trial participants is planned. Children will undergo liver biopsy before initiating therapy. Samples of blood, genomic DNA, and liver tissue will be stored in a central repository. The clinical trial is expected to begin enrollment by mid 2004. An ancillary study policy has yet to be officially developed but will be placed on this website when it becomes available.
  
  
• Viral Resistance to Antiviral Therapy of Chronic Hepatitis C (Virahep C): This prospective clinical trial will study peginterferon and ribavirin therapy in previously untreated patients with chronic hepatitis C infected with genotype 1. The Virahep C study is a cooperative agreement with eight clinical centers that have expertise in treating patients with hepatitis C, a data coordinating center, and four ancillary study sites. In January 2004, this study completed enrollment of approximately 400 adult patients with hepatitis C infected with genotype 1. Half of the patients are African-Americans and half, Caucasian. The trial includes careful viral kinetic studies during the first 28 days of therapy, focusing upon defining the pattern and rapidity of hepatitis C virus inhibition. The goals of the study are to elucidate the response rates of African-Americans to the current optimal therapy of hepatitis C as well as to evaluate factors predictive of a response, which has typically been lower in this population than in Caucasians. Another important goal of this study is to help delineate the causes of resistance to antiviral therapy in hepatitis C, and, for this reason the cooperative agreement already includes funding for four ancillary studies-viral genetics, host genetics, immunology, and interferon-signaling. Applications for ancillary studies of Virahep C will only be accepted in areas not currently being investigated by the ancillary studies groups. Information on Virahep-C and its ancillary study policies is available at their website:  www.virahepc.org 
  
  
• Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial: This prospective, randomized, controlled clinical trial is studying long-term therapy with peginterferon in patients with chronic hepatitis C. Patient enrollment began in 2000 and was completed in 2003 at 10 clinical centers, which are supported by a data coordinating center, virological testing center, and central sample repository. Patients with chronic hepatitis C and advanced fibrosis or cirrhosis on liver biopsy who have failed to respond to a previous course of interferon alfa were enrolled in this study. Patients were initially treated with a 24-week course of peginterferon alfa-2a and ribavirin. Patients who remained hepatitis C virus RNA positive were then randomized to receive maintenance, low-dose peginterferon or to be followed on no treatment. Liver biopsies were done before enrollment and after 2 and 4 years of treatment or follow-up. The endpoints are development of cirrhosis, hepatic decompensation, hepatocellular carcinoma, death, or liver transplantation. More than 1,000 patients have been randomized into HALT-C and are being followed in a standardized fashion with regular assessment of the liver disease viral levels and evidence for hepatic decompensation and hepatocellular carcinoma. Ancillary studies of fibrosis markers, quantitative tests of hepatic function, markers for hepatocellular carcinoma, immunological features of disease and virology are currently funded. Serum samples collected at multiple time points are now being stored. DNA and liver tissue are also stored. Information on HALT-C and its ancillary study policies is available at the study's website:  www.haltctrial.org/.
  
  
• Drug-Induced Liver Injury Network (DILIN): Both a prospective and retrospective database containing cases of drug-induced liver disease, DILIN is funded by a cooperative agreement and includes five clinical centers and a central data coordinating center. This network was initiated in 2003, and protocols for the retrospective and prospective studies will be available by mid-2004. The goals of DILIN are to establish a database of well-characterized cases of drug-induced liver injury and controls with matching serum, DNA, and tissue samples that will facilitate research on the mechanisms of hepatic injury due to drugs. Cases of liver injury due to herbal medications are also included. DILIN will develop standardized definitions of drug-induced liver disease and standardization of scoring systems for causality. Ancillary studies to DILIN focusing on mechanisms of liver cell injury due to the candidate drug are strongly encouraged. Information on when the DILIN ancillary study policy will become available can be found in the future at this website.
  
  
• High-dose Ursodiol Therapy of Primary Sclerosing Cholangitis (HUSC): HUSC is a multi-center placebo-controlled trial of ursodiol in primary sclerosing cholangitis (PSC). A total of 150 patients with previously untreated PSC without cirrhosis will be enrolled into this study which is being conducted at five U.S. medical centers. After initial evaluation, patients will be randomly assigned to receive high doses of ursodiol (20-25 mg/kg/day) or placebo for two years. Patients will undergo medical evaluation, endoscopic retrograde cholangiography, and liver biopsy before randomization and again at two-year intervals. The endpoints of therapy are progression of hepatic fibrosis, liver decompensation, liver transplantation, or death. Enrollment began in January 2003. Samples of serum and DNA from patients are maintained in a central repository. Information on HUSC and its ancillary studies policy will be available on this website.
  
  
• Look AHEAD (Action for Health in Diabetes): This study is a 16-center, randomized clinical trial investigating the long-term health consequences of weight loss. The Look AHEAD cohort comprises approximately 5,000 overweight or obese participants with type 2 diabetes, aged 45-75. Participants are randomized to one of two interventions: an intensive lifestyle intervention designed to produce and sustain weight loss over the long term or a diabetes support and education arm. Participants will be followed for a total of 9 to 11.5 years from randomization. Because of a heavy existing ancillary study burden, Look AHEAD will be open primarily to ancillary studies that propose using existing stored serum, plasma, or DNA samples or that involve little additional burden to participants. The study has a well-defined ancillary study policy and process for submission of ancillary studies to be approved by the Ancillary Studies Committee. The policy and online proposal submission site may be found at:  http://lookahead.phs.wfubmc.edu/index.cfm?fuseaction=public_sitemap
  
  
• LABS (Longitudinal Assessment of Bariatric Surgery) Consortium: The LABS consortium comprises six clinical centers and a data coordinating center. The goal of LABS is to facilitate coordinated clinical, epidemiological, and behavioral research in the field of bariatric surgery, through the cooperative development of common clinical protocols and a bariatric surgery database that will collect information from participating clinical centers. LABS will help pool the necessary clinical expertise and administrative resources to facilitate the conduct of multiple clinical studies in a timely, efficient manner. Also, the use of standardized definitions, clinical protocols, and data-collection instruments will enhance the investigator's ability to provide meaningful evidence-based recommendations for patient evaluation, selection, and follow-up care. The consortium was funded in September 2003. The investigators have collaboratively developed a core database and clinical protocols, and subject enrollment began in early 2005. Further information about LABS and its policies are available on the LABS website. This NIDDK website has information on the ancillary studies policy. The study has a well-defined ancillary study policy and process for online submission of ancillary studies to be approved by the Ancillary Studies Committee. The policy and online proposal submission site may be found at: www.niddklabs.org.
  
  
• Adolescent Bariatrics: Assessing Health Benefits and Risks (Teen-Longitudinal Assessment of Bariatric Surgery [Teen-LABS]). The Teen-LABS consortium is made up of four clinical centers and a data coordinating center. The goal of Teen-LABS is to facilitate coordinated clinical, epidemiological, and behavioral research in the field of adolescent bariatric surgery, through the cooperative development of common clinical protocols and a bariatric surgery database that will collect information from participating clinical centers performing bariatric surgery on teenagers. Teen-LABS will help pool the necessary clinical expertise and administrative resources to facilitate the conduct of multiple clinical studies in a timely, efficient manner. Also, the use of standardized definitions, shared clinical protocols, and data-collection instruments will enhance investigators' ability to provide meaningful evidence-based recommendations for patient evaluation, selection, and follow-up care. In addition to investigating surgical outcomes, another broader goal of Teen-LABS is to better understand the etiology, pathophysiology, and behavioral aspects of severe obesity in youth and how this condition affects human beings over time.

  The consortium was funded in June 2006. The investigators have collaboratively developed a core database and shared clinical protocols, and subject enrollment is planned to begin in early 2007. This NIDDK website has detailed information on general ancillary studies policies and procedures. Further information about Teen-LABS and its specific policies are available on the Teen-LABS website. The study has a well-defined process for online submission of ancillary studies for review by the Teen LABS Ancillary Studies Committee. The policy and online proposal submission site may be found at:  http://www.cincinnatichildrens.org/research/project/teen-labs/.
  

• The Pediatric Acute Liver Failure (PALF) Study:  This multi-center, multi-national collaborative group of pediatric clinical liver centers is aimed at identifying, characterizing, and developing management strategies for infants, children, and adolescents who present with acute liver failure (ALF). In addition to a database of pediatric patients with ALF, a clinical trial is being conducted to test whether the drug N-acetylcysteine (NAC) improves outcome (survival) for patients with ALF not caused by acetaminophen overdose. The ancillary studies policy can be found at: Ancillaries Studies Guidelines and Policies (pdf). Additional information can be obtained at:  http://www.palfstudy.org.
  

• Acute Liver Failure Study Group (ALFSG):  The Acute Liver Failure Study Group is collecting biosamples and information on the natural history, causes and outcomes of Acute Liver Failure in the United States. In addition to the database, a clinical trial conducted to test whether the drug N-acetylcysteine (NAC) improves outcome (survival) for patients with Acute Liver Failure not caused by acetaminophen overdose has recently been completed. Results should be available in the near future. Additional information can be obtained at: http://www8.utsouthwestern.edu/utsw/cda/dept25203/files/89624.html

• The Gastroparesis Clinical Research Consortium (GpCRC): The GpCRC is focusing on the etiology, natural history, and therapy of gastroparesis. The goal of this consortium is to perform clinical, epidemiological, and therapeutic research in gastroparesis and provide an infrastructure that can rapidly and efficiently design and conduct clinical trials for effective medical, surgical, or other interventions to improve treatment of patients with gastroparesis. The GpCRC studies comprise well characterized individuals with diabetic, surgical, and idiopathic gastroparesis. The GpCRC encourages external investigators, as well as GpCRC investigators, to develop ancillary study proposals. The ancillary studies policy can be found at: Ancillaries Studies Guidelines and Policies (pdf). Additional information can be obtained at:  http://www.jhucct.com/gpcrc.

For studies related to Kidney, Urologic and Hematologic Diseases contact John Kusek at (301) 594-7735 or by e-mail at kusekj@extra.niddk.nih.gov

• Chronic Renal Insufficiency Cohort (CRIC) Study: CRIC is a longitudinal cohort study of 3,000 participants recruited from seven clinical centers and followed for up to five years. The cohort will include racially and ethnically diverse (40% white/Caucasian, 40% African American, and 20% other) group of adult patients, ages 21-74, with mild to moderate chronic renal insufficiency, approximately half of whom will have diagnosed diabetes mellitus. The study hypotheses are (1) there is a set of non-traditional risk factors associated with both progression of chronic renal insufficiency and development of end-stage renal disease and (2) there is a set of non-traditional risk factors associated with cardiovascular disease and measures of cardiovascular disease progression in the setting of chronic renal insufficiency. Participants are followed annually at in-clinic visits with interim telephone contact. A sub-cohort of 1,000 study participants will have their kidney function measured with radio-labeled iothalamate. A sub-cohort of the same size will also undergo electron beam tomography to assess coronary calcification. All study participants will have an echocardiogram at year 1 and year 4 of follow-up. The design of the study has been published (Feldman H et al. J Am Soc Nephrol 2003, 14 (Suppl 2): S148-153). Recruitment to the study is currently underway. The ancillary study policy is available at Ancillary Studies Policy (pdf-38KB).
  
  
• The African American Study of Kidney Disease and Hypertension (AASK) Cohort Study: This multi-center, prospective observational study is an extension of the AASK Trial, a multi-center, randomized clinical trial of the effects of two blood pressure levels and three antihypertensive drug regimens on the loss of kidney function among African Americans with hypertensive nephrosclerosis. (Results of the clinical trial have been published: Agodoa L. et al. JAMA 285:2719-2728, 2001 and Wright JW et al. JAMA 288:2421-2431, 2002). A description of the cohort study has also been published (Appel L et al. J Am Soc Nephrol 14(Suppl 2): S166-172, 2003). The major objective of the study is to identify risk factors for clinical outcomes of kidney disease (the primary renal outcome is a composite clinical outcome defined as the occurrence of a marked reduction in kidney function, end-stage renal disease, or death) and cardiovascular disease. Serum creatinine is measured at baseline and every six months thereafter. Questionnaires that focus on risk factors are administered annually. Blood for DNA has been collected once. On an annual basis, a variety of measurements are performed on blood and urine. At baseline and every other year, two-dimensional echocardiograms and 24-hour ambulatory blood pressure recordings are obtained. The cohort has been fully recruited and the study is in the follow-up phase. The ancillary study policy is currently under development and will become available at this website.
  
  
• Dialysis Access Consortium (DAC): The consortium was established to conduct randomized, controlled clinical trials on vascular access among hemodialysis patients. The DAC consists of seven clinical centers recruiting patients to two concurrent clinical trials. One trial, the Clopidogrel Prevention of Early Fistula Thrombosis Trial, will enroll 1,284 patients (recruitment is ongoing). Patients undergoing creation of new native arteriovenous fistula are randomized to treatment with clopidogrel or placebo for six weeks following fistula creation surgery. The primary outcome is fistula patency at six weeks. A second clinical trial examines the effect of dipyridamole (Aggrenox) to prevent access failure in patients who receive a new arteriovenous graft. The primary study outcome is primary, unassisted patency. This outcome is defined as the time from access creation until the first occurrence of either access thrombosis or an access procedure (such as angioplasty) that is performed to restore access patency. Ancillary Studies Policy (pdf-20KB)
  
  
• Boston Area Community Health (BACH) Survey: This survey is a cross-sectional, population-based prevalence study of symptoms associated with a range of urologic conditions, including chronic pelvic pain, urinary incontinence, and interstitial cystitis in men and women and erectile dysfunction, benign prostatic hyperplasia, and hypogonadism in men only. A total of 6,000 subjects, ages to 30 to 79, randomly sampled from the city of Boston, equally divided among men and women, will be recruited. The study population will be equally represented by Black Americans (non-Hispanic), Hispanic race/ethnicity, and Caucasians (non-Hispanic). Recruitment is approximately halfway to goal. Serum samples from men only have been archived. An ancillary study policy is currently under development and will be posted on this website as soon as it becomes available.
  
  
• Complementary and Alternative Medicine for Urological Symptoms (CAMUS): A multi-center clinical trial, sponsored by the NIDDK, the National Center for Complementary and Alternative Medicine, and the Office of Dietary Supplements, CAMUS will compare the effects of two phytotherapies, saw palmetto and Pygeum africanum, and an active comparator (alpha blocker) on the progression of benign prostatic hyperplasia compared to placebo. The trial will recruit a total of approximately 3,000 men. Recruitment is anticipated to begin in the summer 2004. An ancillary study policy is currently under development and when available, will be posted on this website.
  
  
• Minimally Invasive Surgical Therapy (MIST): MIST is multi-center, randomized clinical trial that will compare the effects of drug therapy (combined treatment with finasteride and alfuzosin) and two minimally invasive surgical therapies (transurethral needle ablation and transurethral microwave therapy). The primary outcome is treatment failure within 36 months, determined according to an objective set of criteria. Approximately 700 men will be recruited into the trial beginning in spring 2004. An ancillary study policy is currently under development and will be included in this website as soon as it becomes available.
  
  
• Urinary Incontinence Treatment Network (UITN): The network was established to plan and conduct randomized clinical trials in women and men with urinary incontinence. The first clinical trial undertaken by the network (the Stress Incontinence Surgical Treatment Efficacy Results or SISTEr) is a comparison between two commonly used surgical techniques for women with stress urinary incontinence, the Burch urethropexy and the autologous rectus fascial sling procedures. The primary outcome of the trial is the overall treatment success (no urinary leakage and no re-treatment for stress urinary incontinence and treatment success specific to stress urinary incontinence). Six hundred and fifty women will be recruited into this trial. It is anticipated that recruitment will be completed in spring 2004. The second clinical trial planned by the UITN is the Behavior Enhances Drug Reduction of Incontinence (BE-DRI). The purpose of this trial is to compare the effects of two interventions, drug therapy alone and combination drug therapy and behavioral treatment, on the frequency of urinary incontinence and success in withdrawing patients from drug therapy. The target population is women with pure or predominant urge incontinence. A sample size of 300 will be recruited beginning summer 2004. Ancillary Studies Policy (pdf-77KB)
  
  
• Family Investigation of Nephropathy of Diabetes (FIND): A multi-center, collaborative study, FIND aims to identify the genetic basis of nephropathy, especially diabetic nephropathy, using a combination of genetic approaches. Much of the study is focused on collecting sibpairs of various ethnicities for linkage analysis, beginning with a genome scan. Other parts of the study are collecting cases and various types of controls to carry out Mapping by Admixture Disequilibrium (MALD) in Mexican American and African American populations. Recruitment is expected to continue through early 2005, and the initial genome scans will be completed by early 2006. Ancillary Studies Policy (pdf-16KB)
  
  
• Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial: FAVORIT is a multi-center, randomized, double-blind clinical trial. It was designed to determine the effects of whether total homocysteine-lowering treatment with a standard multivitamin augmented by a high-dose combination of folic acid, vitamin B12, and vitamin B6 versus treatment with an identical multivitamin containing no folic acid and Estimated Average Requirement amounts of folic acid, vitamin B12, and vitamin B6, reduces the pooled rate of recurrent and de novo cardiovascular disease outcomes among clinically stable renal transplant recipients who have mild to moderately elevated levels of total homocysteine. The clinical trial is currently in the recruitment phase with a total sample size of 4,000. Ancillary Studies Policy (pdf-24KB)
  
  
• Pediatric Chronic Renal Insufficiency Cohort Study: The goals of this multi-center prospective epidemiological study of chronic kidney disease in 600 children, ages 1-16 years, are to determine risk factors for progression of kidney disease and to examine the impact of chronic kidney disease on neurocognitive development and risk factors for cardiovascular disease and growth. The protocol for this study is currently under development. The ancillary study policy is also under development and when it becomes available will be found at this website.
  
  
• Focal Segmental Glomerular Sclerosis (FSGS) Trial in Young Adults and Children: This multi-center, randomized clinical trial will compare the efficacy of treatment with cyclosporine to treatment with mycophenalate mofetil combined with oral pulse dexamethasone in patients with steroid-resistant FSGS. Efficacy will be assessed in terms of induction of remission of proteinuria after 52 weeks of treatment and sustained remission after 26 weeks off treatment. A total of 500 patients between the ages of 2-35 years are expected to be recruited beginning in spring 2004. Ancillary Studies Policy (pdf-30KB)
  
  
• Consortium for Radiologic Imagining of Polycystic Kidney Disease (CRISP): CRISP was established to develop innovative imaging techniques and analyses to follow disease progression or to evaluate treatments for autosomal-dominant polycystic kidney disease. The study, currently in its final year, has followed 240 patients with annual glomerular filtration rate evaluation and magnetic resonance imaging to assess changes in renal volume over time.
  
  
• Frequent Dialysis Clinical Trials: In September 2003, the NIDDK awarded four cooperative agreement grants to conduct clinical trials on frequent hemodialysis. The participating centers will investigate whether it is feasible to randomize a representative sample of hemodialysis patients into either (a) conventional thrice-weekly dialysis treatments or (b) one of two forms of frequent dialysis. One trial will compare short daily hemodialysis with conventional dialysis, and the other will compare long nocturnal dialysis with conventional dialysis. Patients will be followed for at least six months, and intermediate outcomes related to anemia, nutritional status, blood pressure, left ventricular hypertrophy, exercise tolerance, medication use, and hospitalizations will be tracked. An ancillary study policy for this trial is currently under development and will be posted at this website.
  
  
• HALT-PKD: This multi-center, randomized clinical trial of hypertensive polycystic kidney disease patients will assess the effect of rennin angiotensin blockage on renal disease progression (changes in renal volume and glomerular filtration rate). HALT-PKD is currently in the protocol development phase. The ancillary study policy is under development and will be posted on this website as soon as possible.
  
  
• Chronic Prostatitis Collaborative Research Network: This network was established to conduct randomized controlled clinical trials of promising treatments for men suffering from chronic prostatiis/chronic pelvic pain syndrome (CP/CPPS). The Network consists of ten clinical centers (recruiting sites) with two satellite recruiting sites and a data coordinating center. The Network is currently recruiting for a clinical trial of Alfuzosin in newly diagnosed/treatment naïve CP/CPPS patients. A second clinical trial of Pregabalin is planned.
  
  
• Interstitial Cystitis Clinical Research Network (ICCRN): This network was established to conduct randomized controlled clinical trials among men and women with interstitial cystitis and/or painful bladder syndrome. The ICCRN consists of 10 clinical centers (recruiting sites) and a data coordinating center. Currently, the ICCRN is recruiting for a clinical trial to evaluate the efficacy and safety of amitriptyline in newly diagnosed/treatment naïve patients with interstitial cystitis/painful bladder syndrome.

• Randomized Intervention for Vesicoureteral Reflux (RIVUR): This multicenter, randomized, double-blind, placebo-controlled trial is designed to determine whether daily antimicrobial prophylaxis is superior to placebo in preventing recurrence of urinary tract infection (UTI) in children with vesicoureteral reflux (VUR). The basic eligibility criteria are: (1) age at randomization of at least 2 months, but less than 6 years, (2) a diagnosed first febrile or symptomatic UTI (F/SUTI ) within 42 days prior to randomization that was appropriately treated, and (3) presence of Grade I-IV VUR based on voiding cystourethrogram (VCUG). Children with co-morbid urologic anomalies, history of allergy to the study intervention, and other conditions or chronic diseases that might interfere with completing the study protocol will be excluded. Patients will be randomly assigned to treatment for 2 years with daily antimicrobial prophylaxis (trimethoprim-sulfamethoxazole) or placebo. The study is designed to recruit 600 children (approximately 300 in each treatment group) over an 18-24 month period. The protocol will encourage prompt evaluation of children with UTI symptoms and early therapy of culture-proven UTIs. It is expected that approximately 10% of children will have to discontinue study medication due to allergic reactions. Assuming a 20% placebo event rate and 10% non-compliance rate, the study has 83% power to detect an absolute 10% event rate in the antimicrobial prophylaxis group. If the placebo event rate is instead 25%, power is 97% to detect an absolute 10% event rate in the treated group, even if non-compliance is as high as 15%. The primary endpoint is recurrence of F/SUTI. In addition, patients will be evaluated for secondary endpoints related to renal scarring and antimicrobial resistance. Scarring will be determined based on renal scintigraphy by 99mTc dimercaptosuccinic (DMSA) scan. Quality of life, compliance, safety parameters, utilization of health resources, and change in VUR will be assessed periodically throughout the study.

For studies related to Diabetes Mellitus contact Sanford Garfield at (301) 594-8803 or by e-mail at GarfieldS@extra.niddk.nih.gov

• Diabetes Prevention Program Outcomes Study (DPPOS): DPPOS is the long-term follow-up of the Diabetes Prevention Program (DPP), which was initiated in 1996 and ended one year early (May 2001) as a result of highly significant and positive study outcomes as reported in the New England Journal of Medicine ( N Engl J Med 2002 Feb 7;346 (6):393-403). These results demonstrated that lifestyle and drug interventions could markedly reduce the risk for developing type 2 diabetes in a group at high risk due to the presence of impaired glucose tolerance, by 58 percent for lifestyle and 31 percent for metformin. Importantly, it was shown that interventions were similarly effective in men and women and in all of the ethnic-racial groups that were included in the study. The DPP included 45 percent of the study cohort from African American, Hispanic American, Asian American, Pacific Islander, and American Indian populations. In addition, 20 percent of the study population was older than age 60, and 68 percent of participants were women. While the primary goal of the DPP was to prevent the development of diabetes, an important secondary goal was to decrease the rate of cardiovascular disease and its risk factors. These clinically important outcomes were considered as secondary during the DPP due to a lack of sufficient power in the time allotted to the study to detect potential differences between the treatment groups. The DPP cohort being followed in the DPPOS is the largest study population with pre-diabetes and the only population with type 2 diabetes studied from time of onset. The study cohort will provide insights regarding the clinical course of metabolic disorders and cardiovascular disease as well as information on the persistence of the prevention of type 2 diabetes and the maintenance of sustained weight loss. Ancillary Studies Policy (pdf-28KB)
  
  
• Studies to Treat or Prevent Pediatric Type 2 Diabetes (STOPP-T2D): This multi-site consortium is developing trials related to type 2 diabetes in the pediatric population. Two trials are currently being supported under the STOPP-T2D consortium:
  
  
  • Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) is a 12-site clinical trial to assess the best treatment for type 2 diabetes in the pediatric population. The TODAY cohort will consist of 750 youth between the ages of 10 and 17 years, who will be randomized to one of three arms: (1) metformin alone; (2) metformin plus rosiglitazone; and (3) metformin plus an intensive lifestyle intervention. All participants will receive standardized diabetes education. The primary outcome will be time to rescue, defined as a hemoglobin A1c > 8.0 percent for 6 months. Secondary outcomes include beta cell function, comorbidities (dyslipidemia, hypertension), microvascular complications, side effects/QOL, and cost analysis. Enrollment will begin in early 2004. The ancillary study policy for the STOPP-T2D treatment trial can be found at  www.todaystudy.org.
    
    
  • The STOPP-T2D prevention trial is a multi-center, school-based trial to decrease or prevent the development of risk factors for type 2 diabetes in middle school children. The STOPP-T2D study will deliver a three-year intervention, starting in 6th grade. There will be three components: (1) enhanced physical activity in the school by increasing the time devoted to moderate-vigorous activity in gym class; (2) environmental change in the school targeting the food service, by changing foods available in the cafeteria and vending machines; and (3) behavior curriculum aimed at increasing physical activity in and out of school, decreasing sedentary behavior out of school, and changing dietary habits. The group is currently conducting a series of pilots to assess the feasibility and efficacy of components of the intervention. If the pilots are successful, the full intervention is expected to commence in September 2005. The ancillary study policy for the STOPP-T2D prevention trial will appear on the website established for this PA.
  
  
  
• Type 1 Diabetes TrialNet: This international network of clinical research groups (and core support facilities) aims to recruit patients and to support studies that may eventually result in an improved understanding of the pathogenesis and prevention of type 1 diabetes. Type 1 Diabetes TrialNet will perform intervention studies to preserve pancreatic beta cell function and prevent the onset of type 1 diabetes in patients at risk for the development of type 1 diabetes. The clinical centers participating in TrialNet will be involved in the design and execution of pilot and expanded studies of new agents to prevent or to ameliorate type 1 diabetes, and in natural history and genetics studies in populations screened for or enrolled in these studies. A steering committee composed of principal investigators from the clinical centers, operations coordinating center, data monitoring unit, core laboratories, and NIH program officers will determine the actual studies to be performed within TrialNet. Additional information on Type 1 Diabetes TrialNet is available at www.diabetestrialnet.org/en/public/intro.html, and information regarding submission of ancillary studies for consideration by the TrialNet Steering Committee can be obtained by contacting the GWU Biostatistics Center via their website at   www.bsc.gwu.edu/bsc/studies/trialnet.html.
  
  
• The Epidemiology of Diabetes Interventions and Complications Study (EDIC): The Epidemiology of Diabetes Interventions and Complications Study (EDIC) is an observational study examining the risk factors associated with the long-term complications of type 1 diabetes. The study began in 1994 and follows the 1441 participants previously enrolled in the Diabetes Control and Complications Trial (DCCT). For more information, see: EDIC Study (pdf-14KB)
  

  The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study is entering its 21st year. From 1983 to 1989, 1441 type 1 diabetic participants were recruited into the DCCT. They were randomly assigned to 2 treatment groups, intensive and conventional for an average of 6.5 years of randomized treatment time. The DCCT ended in 1993 after demonstrating conclusively that intensive treatment (mean HbA1c 7.2%) reduced the development and progression of diabetic retinopathy, nephropathy and neuropathy, compared to conventional treatment (mean HbA1c 9.0%). In 1994, 96% of the participants were enrolled in EDIC for regular observational follow-up of metabolic and complications status, using similar methods as in the DCCT. Diabetes care is obtained from the EDIC participants' own physicians.

  The primary aim of EDIC is to examine the long-term effects of conventional vs. intensive diabetes treatment received during the DCCT on the subsequent development and progression of microvascular, neuropathic and cardiovascular complications. This involves studying the influence of genetic factors and other factors such as HbA1c, blood pressure, lipid levels, and treatment modalities on the development and progression of these complications. The ancillary studies policy can be found at: Ancillaries Studies Guidelines and Policies
  
  

• The Environmental Determinants of Diabetes in the Young" (TEDDY) consortium: The goal of the "The Environmental Determinants of Diabetes in the Young" (TEDDY) consortium is to organize international efforts to identify infectious agents, dietary factors, or other environmental factors, which trigger type 1 diabetes in genetically susceptible individuals. Materials to be made available to researchers will include: DNA samples (cell lines) from individuals at risk of developing diabetes; phenotype data from these individuals; Plasma, serum, mRNA, stool, and other samples from these individuals; data from genetic and laboratory analysis of stored DNA, plasma, and serum samples. The TEDDY consortium, funded in September 2002, plans to create a central repository of above mentioned data and biological samples. The consortium will also develop plans for access and distribution of materials. For more information go to  http://www.teddystudy.org.
  
  
• The SEARCH for Diabetes Youth Study: The SEARCH for Diabetes Youth study is an observational study initiated in 2000 in 6 sites in the US. The primary aims of SEARCH are to: 1) estimate the prevalence and incidence of type 1, type 2, and other types of diabetes overall and by age, gender and race/ethnicity; 2) develop efficient and practical methods to classify diabetes by type; and 3) describe and compare the clinical presentation and course of type 1, type 2 and other types of diabetes. The secondary aims of the study are to describe by type: 1) the distribution of risk factors for selected micro- and macro-vascular disease complications; 2) the distribution of selected acute and chronic complications; and 3) health care utilization, processes of care and quality of life. Additional information can be obtained at:   www.searchfordiabetes.org/.
  
  
• Targeting Inflammation Using Salsalate for Type 2 Diabetes (TINSAL-T2D): The TINSAL-T2D study is a multi-center, randomized, double-blinded, placebo-controlled, parallel-group clinical trial. The primary objective of the study is to determine whether salicylates represent a new pharmacological option for glycemic control in patients with type 2 diabetes. The primary outcome for the study is change in HbA1c level from baseline to week 26 in the intent-to-treat (ITT) population with last observation carried forward. The study is conducted in two stages. The first stage is to select a dose of salsalate that is both well-tolerated and demonstrates a trend toward improvement in glycemic control. The second stage is to evaluate (1) the effects of salsalate on glycemic control (HbA1c), (2) the tolerability of salsalate use, and (3) the effects of salsalate on measures of inflammation, the metabolic syndrome, and cardiac risk. The implementation of the second stage is predicated on the successful selection of a dose in the first stage. The ancillary studies policy can be found at: Ancillaries Studies Guidelines and Policies (pdf). Additional information can be obtained at:   http://www.tinsal-t2d.org.