Protocol Number: 09-DK-0056

Title:

Novel Therapy Combining Regenerative Stimuli Immunomodulation to Preserve Beta Cell Function in New Onset Type 1 Diabetes

Number:

09-DK-0056

Summary:

Background:

- Type 1 diabetes (T1D) occurs when the immune system attacks insulin-producing cells (beta cells) in the pancreas, resulting in their death.

- Insulin injections currently are the best method for controlling blood sugar in individuals with T1D. However, animal studies have shown that the drugs sitagliptin and lansoprazole can help reverse beta cell damage or develop new beta cells. In addition, Diamyd has been shown to weaken the immune process that attacks pancreatic beta cells.

Objectives:

- To find out whether a combination treatment of sitagliptin, lansoprazole, and Diamyd will help maintain functioning beta cells and/or cause new beta cells to form.

- To determine how the drug combination affects insulin doses and blood sugar control.

- To determine whether the drug combination affects the immune response involved in T1D.

Eligibility:

- Patients 16 to 30 years of age diagnosed (within the preceding 4 months) with laboratory-confirmed diabetes caused by an immune response directed against pancreatic beta cells.

Design:

- The study, lasting approximately 25 months, will consist of four periods: screening period (laboratory and clinical testing), run-in period (close monitoring of blood glucose via Web-based program; 4-6 weeks), active treatment period (12 months), and follow-up period (12 months).

- Study participants will be randomly assigned to two groups:

-Group A (placebo): Participants will receive insulin therapy adjusted to keep the blood sugar as close to normal as possible, 2 sugar pills (in place of sitagliptin and lansoprazole), and salt water injections (in place of Diamyd).

-Group B (treatment): Participants will receive insulin therapy as in Group A, sitagliptin (100 mg once daily for adults; 50 mg once daily for children) and lansoprazole (30 mg twice daily for adults; 30 mg once daily for children) in pill form, and Diamyd injections (at initial treatment, 4 weeks, and 12 weeks).

- Evaluations during the active treatment period:

-Mixed meal studies: Participants in Groups A and B will drink the milkshake-like Boost High Protein to stimulate insulin production; blood will be drawn immediately thereafter and every 30 minutes for 2 hours to measure hormones in the blood stream. This procedure will be done a total of 5 times during the 25-month period.

-Frequently sampled intravenous glucose tolerance test: After a 12-hour overnight fast, participants will be given IV glucose for 1 to 2 minutes in addition to a small amount of insulin. Blood will be collected at specified frequencies for up to 3 hours to measure sensitivity to insulin. This procedure will be done a total of 3 times during the 25-month period.

- Evaluations during the follow-up period:

-Blood and urine laboratory tests in addition to mixed meal studies.

Sponsoring Institute:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

1. Recently diagnosed (within the preceding 4 months of screening) diabetes clinically consistent with T1D:

A. Positive for anti-GAD antibody.

B. BMI between 19 and 28 kg/m2; for those between the ages of 16 to 18, the BMI must be within 10th to 90th percentile for the age.

2. Ages between 16 and 30 years, inclusive

3. Random plasma C-peptide level of equal to or greater than 0.20 nmol/L

4. Willingness and ability to institute intensive insulin-based glucose management.

EXCLUSION CRITERIA:

1. Diabetic nephropathy with a creatinine clearance less than 60 cc/min or 24 hour urine albumin greater than 300 mg

2. Insulin requirements greater than 0.8 units/kg/day at the end of the run-in period

3. Regular use of a proton pump inhibitor within 3 months of enrollment

4. Use of GLP-1R agonist or DPP-4 inhibitor within 6 months prior to enrollment

5. Use of immunosuppressive therapy in the preceding 12 months

6. Evidence of chronic infection, for example, known human immunodeficiency virus (HIV) or hepatitis

7. History of any malignancy other than a treated basal or squamous skin cancer

8. Any chronic medical condition to unduly increase risk for the potential enrollee as judged by study investigators

9. Pregnancy, breastfeeding or planned pregnancy within two years, women of reproductive age not using an effective mode of contraception and unwilling to continue adequate contraception until 1 year after the last study drug administration

10. Any other co-existing condition/circumstances that would make patient unsuitable to participate in the study, as deemed by the investigators. For example, study investigators would exclude any potential candidate with any of the following (but the list is not inclusive):

A. Clinically significant past history of an acute reaction to vaccines or other drugs

B. Recent participation in other clinical trials with a new chemical entity

C. A history of alcohol or drug abuse

D. Significant neurological conditions like epilepsy, head trauma, or cerebrovascular accidents

Special Instructions:

Currently Not Provided

Keywords:

Type I Diabetes

Preserve Beta Cell Function

Sitagliptin

Lansoprazole

GAD65 (Diamyd)

Recruitment Keyword(s):

Diabetes

Type 1 Diabetes

T1DM

Condition(s):

Diabetes Mellitus Type 1

Autoimmune Diabetes

Diabetes Mellitus, Autoimmune

Investigational Drug(s):

GAD65 (Diamyd)

Investigational Device(s):

None

Intervention(s):

Drug: Insulin

Drug: Lansoprazole

Drug: Sitagliptin

Biological/Vaccine: Diamyd

Drug: GAD65 (Diamyd)

Supporting Site:

National Institute of Diabetes and Digestive and Kidney Diseases

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Bach JF, Chatenoud L. Tolerance to islet autoantigens in type 1 diabetes. Annu Rev Immunol. 2001;19:131-61.

Lernmark A, BŠrmeier H, Dube S, Hagopian W, Karlsen A, Wassmuth R. Autoimmunity of diabetes. Endocrinol Metab Clin North Am. 1991 Sep;20(3):589-617.

Mathis D, Vence L, Benoist C. beta-Cell death during progression to diabetes. Nature. 2001 Dec 13;414(6865):792-8.

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