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Myocardial Function & FFA Metabolism in HIV Metabolic Syndrome (WU197)
This study is currently recruiting participants.
Verified by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), October 2008
Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00656851
  Purpose

We hypothesize that the hearts of HIV+ people with The Metabolic Syndrome use and oxidize fats and sugars inappropriately, and that this may impair the heart's ability to pump blood. We hypothesize that exercise training or pioglitazone (Actos) will improve fat and sugar metabolism in the hearts of HIV+ people with The Metabolic Syndrome. This study will advance our understanding of cardiovascular disease in HIV+ people, and will test the efficacy of exercise training and pioglitazone for improving insulin resistance, heart metabolism and heart function in this at risk population.


Condition Intervention
HIV Infections
Cardiovascular Disease
Insulin Resistance
HIV Lipodystrophy
The Metabolic Syndrome
Drug: Pioglitazone
Behavioral: Exercise Training

MedlinePlus related topics: AIDS Exercise and Physical Fitness
Drug Information available for: Pioglitazone Pioglitazone hydrochloride Dextrose
U.S. FDA Resources
Study Type: Interventional
Study Design: Diagnostic, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title: Myocardial Function, Free Fatty Acid and Glucose Metabolism in HIV Metabolic Syndrome

Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Myocardial fatty acid and glucose uptake, utilization and oxidation rates [ Time Frame: Weeks 0 and 16 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Myocardial contractile function during systole and diastole [ Time Frame: Weeks 0 and 16 ] [ Designated as safety issue: No ]
  • Carotid intima media thickness [ Time Frame: Week 0 and 16 ] [ Designated as safety issue: No ]
  • Brachial artery reactivity [ Time Frame: Week 0 and 16 ] [ Designated as safety issue: No ]
  • Whole-body lipolysis rate, fatty acid oxidation rate, and glucose disposal rate [ Time Frame: Week 0 and 16 ] [ Designated as safety issue: No ]
  • Fasting lipids and lipoproteins [ Time Frame: Week 0, 2, 4, 6, 8, 10 and 16 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: September 2005
Estimated Study Completion Date: August 2010
Estimated Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Pioglitazone: Active Comparator
Pioglitazone (Actos, 30mg/day for 16 weeks)
Drug: Pioglitazone
30mg/day for 16 weeks
Exercise Training: Active Comparator
Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
Behavioral: Exercise Training
Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks

Detailed Description:

We hypothesize that myocardial free fatty acid and glucose utilization and oxidation rates are dysregulated in HIV+ people with The Metabolic Syndrome in comparison to HIV+ people without The Metabolic Syndrome, and in comparison to HIV-seronegative people with and without The Metabolic Syndrome. We hypothesize that dysregulated myocardial fatty acid and glucose metabolism is associated with impaired heart function (diastolic dysfunction) in HIV+ people with The Metabolic Syndrome. We will use myocardial positron emission tomography, radioactive isotope tracers of palmitate and glucose, and echocardiography to evaluate myocardial metabolism and function. HIV+ people with The Metabolic Syndrome will receive 16wks of exercise training or pioglitazone (Actos), and we will evaluate their potential beneficial effects on myocardial metabolism and function.

  Eligibility

Ages Eligible for Study:   28 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: All participants both with and without metabolic syndrome:

  1. 28-50 years old.
  2. Plasma HIV RNA less than 5,000 copies/mL for previous 3 months OR CD4 count greater than 100 cells/µL for previous 3 months.
  3. Stable for at least the past 3 months on any HAART regimen.
  4. "Normal" blood chemistries for at least 1 month prior to enrollment: platelet count >50,000/mm3, absolute neutrophil count >750/mm3, liver transaminases <2.5x the upper limit of normal (ULN), creatinine <1.3x ULN, albumin >30g/L, creatine kinase <5.9x ULN.

Menstruating women must have a negative urine beta-HCG pregnancy test within 14 days prior to study. To control for potential metabolic effects of alterations in female hormones during the menstrual cycle, all menstruating women will be studied during the follicular phase (serum 17beta-estradiol <165 pg/mL).

Exclusion Criteria:

  1. Frank obesity (BMI >35kg/m2).
  2. Chronic hepatitis B infection (HB surface antigen positive). Active hepatitis C infection (detectable Hep C RNA). Those who have cleared hepatitis B or C infection are eligible.
  3. Diabetes [fasting glucose >125 mg/dL, or fasting insulin >45 µU/mL, or 2-hr glucose >200mg/dL].
  4. Medications or agents that regulate glucose metabolism (e.g., insulin-sensitizers, insulin-secretagogues). Lipid lowering agents that regulate lipid metabolism (i.e. fibrate, statin).
  5. Gestational diabetes, pregnancy, or nursing mothers.
  6. Serum triglycerides ≥ 500 mg/dL.
  7. Hypogonadism [total testosterone <200ng/dL (men) or <15ng/dL (women)]; thyroid disorder [TSH <0.2 or >12µIU/mL]; hypercortisolemia [morning cortisol >22µg/dL]. Replacement testosterone or thyroid hormones to normalize abnormal levels is acceptable, as long as treatment and blood levels have been stable for at least 3 months.
  8. Use of human growth hormone (hGH) or GH-secretagogues (GH-releasing hormone-peptides) within the previous 3 months.
  9. History of serious cardiovascular disease; MI, angina pectoris, heart failure, congenital heart disease, coronary artery disease, coronary artery bypass graft, stroke. Bundle branch block is exclusionary because it limits the interpretability of the resting/exercise ECG. Cardiovascular or physical contraindications to maximal exercise testing on a cycle ergometer.
  10. Uncontrolled hypertension (>140/90 mmHg). Certain antihypertensive medications will be permitted (diuretics, ACE inhibitors) as long as the medication, dose, and blood pressure have been stable for at least 3 months.
  11. Well-trained athletes (defined as >3 exercise training exposures/week; >30min regimented exercise/exposure maintained for at least the prior 4 weeks).
  12. History of or active substance abuse (eg, alcoholism, cocaine, heroin, crack, methamphetamine, phencyclidine).
  13. Active secondary infection. Any significant change in chronic suppressive therapy for an opportunistic infection during 1 month prior to enrollment.
  14. New serious systemic infection during the 3 weeks prior to enrollment.
  15. History of hyperlactatemia or lactic acidosis, esp. with rapid weight loss.
  16. Debilitating-painful myopathy or neuropathy that requires 'assistance' to conduct normal activities of daily living (dressing, hygiene, preparing meals, operating a vehicle). These might affect peripheral substrate metabolism.
  17. Chronic renal insufficiency/failure or other comorbid conditions (eg. cancer, COPD) that alter metabolism.
  18. Pancreatitis, celiac disease, or cirrhosis.
  19. Inadequate macronutrient or energy intake, or malabsorptive disorder.
  20. Dementia or any condition that would prevent voluntary informed consent or compliance.
  21. Other compounds or blinded investigational new drugs that might affect metabolism or confound data interpretation (eg. RU486, interleukin therapy, or cytokine-receptor antagonist).
  22. Oral glucocorticoid or corticosteroid use within previous 3 months.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00656851

Contacts
Contact: Sherry Lassa-Claxton, RD, MS 314-362-7637 slasscla@im.wustl.edu
Contact: Todd Cade, PT, PhD 314-286-1432 tcade@wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Sherry Lassa-Claxton, RD, MS     314-362-7637     slasscla@im.wustl.edu    
Contact: Todd Cade, PT, PhD     314-286-1432     tcade@wustl.edu    
Sub-Investigator: Todd Cade, PT, PhD            
Sub-Investigator: Robert Gropler, MD            
Sub-Investigator: Victor Davila-Roman, MD            
Principal Investigator: Kevin Yarasheski, PhD            
Sponsors and Collaborators
Investigators
Principal Investigator: Kevin Yarasheski, PhD Washington University School of Medicine
  More Information

Responsible Party: Washington University School of Medicine ( Kevin E. Yarasheski/Principal Investigator )
Study ID Numbers: DK59531, HRPO 05-0976
Study First Received: April 10, 2008
Last Updated: October 7, 2008
ClinicalTrials.gov Identifier: NCT00656851  
Health Authority: United States: Federal Government

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
HIV/AIDS
Heart disease
Diabetes
Cardiovascular disease risk
Dyslipidemia
Visceral adiposity
treatment experienced

Study placed in the following topic categories:
Obesity
Sexually Transmitted Diseases, Viral
Metabolic Diseases
Heart Diseases
Pioglitazone
Skin Diseases
Acquired Immunodeficiency Syndrome
Diabetes Mellitus
Immunologic Deficiency Syndromes
Virus Diseases
Hyperinsulinism
HIV Infections
Lipodystrophy
Sexually Transmitted Diseases
Insulin Resistance
Metabolic disorder
Glucose Metabolism Disorders
Retroviridae Infections
Dyslipidemias
Lipid Metabolism Disorders

Additional relevant MeSH terms:
RNA Virus Infections
Slow Virus Diseases
Disease
Immune System Diseases
Physiological Effects of Drugs
Infection
Pharmacologic Actions
Pathologic Processes
Hypoglycemic Agents
Skin Diseases, Metabolic
Syndrome
Lentivirus Infections
Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 16, 2009