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Myocardial Function & FFA Metabolism in HIV Metabolic Syndrome (WU197)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kevin Yarasheski, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00656851
First received: April 10, 2008
Last updated: August 19, 2013
Last verified: August 2013

April 10, 2008
August 19, 2013
September 2005
August 2009   (final data collection date for primary outcome measure)
  • Myocardial Glucose Utilization Rate [ Time Frame: Weeks 0 and 16 ] [ Designated as safety issue: No ]
    Radio-tracer (11C-glucose) and positron emission tomography quantification of myocardial glucose utilization rate. The rate at which glucose exits the blood, enters the muscle cells in the left ventricle, and is metabolized (ATP generation, glycolysis, glycogenolysis, or lactate production). Total glucose utilization rate in the left ventricle of the heart.
  • Myocardial Glucose Utilization Rate Per Unit Insulin [ Time Frame: Weeks 0 and 16 ] [ Designated as safety issue: No ]
    Radio-tracer (11C-glucose) and positron emission tomography quantification of myocardial glucose utilization rate per unit of plasma insulin. Total glucose utilization rate in the left ventricle of the heart expressed per unit of the circulating plasma insulin concentration.
  • Myocardial Fatty Acid Utilization Rate [ Time Frame: Weeks 0 and 16 ] [ Designated as safety issue: No ]
    Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid utilization rate. The rate at which palmitate exits the blood, enters the muscle cells in the left ventricle, and is metabolized (oxidation, re-esterification).
  • Myocardial Fatty Acid Oxidation Rate [ Time Frame: Weeks 0 and 16 ] [ Designated as safety issue: No ]
    Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid oxidation rate.
  • Myocardial Fatty Acid Esterification [ Time Frame: Weeks 0 and 16 ] [ Designated as safety issue: No ]
    Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid esterification as a % of total fatty acid extraction
Myocardial fatty acid and glucose uptake, utilization and oxidation rates [ Time Frame: Weeks 0 and 16 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00656851 on ClinicalTrials.gov Archive Site
  • Myocardial Contractile Function During Diastole [ Time Frame: Weeks 0 and 16 ] [ Designated as safety issue: No ]

    Echocardiographic quantification of (E/A) early to late diastolic filling velocity. Aria transfer blood to the ventricles in 2 steps:

    1. blood collected in the atria falls into the ventricles when the atrioventricular valves opens. In the left heart, the velocity at which the blood moves during this initial action is called the early or "E" filling velocity.
    2. residual blood in the atria, is emptied during diastole by atrial contraction. The velocity of the blood during atrial contraction is the "A" (for atrial) filling velocity. These are expressed as a ratio (E/A). If A exceeds E velocity (ratio <1.0) this is a clinical marker of diastolic dysfunction. This can occur when the left ventricular wall becomes so stiff as to impair proper filling, which can lead to diastolic heart failure.
  • Myocardial Contractile Function During Systole [ Time Frame: Weeks 0 and 16 ] [ Designated as safety issue: No ]
    Echocardiographic quantification of E' wall velocity during systole averaged at the lateral wall and septum
  • Fasting Lipids and Lipoproteins [ Time Frame: Week 0 and 16 ] [ Designated as safety issue: Yes ]
    fasting serum triglycerides, LDL-, and HDL-cholesterol concentrations
  • Fasting Glucose Insulin and HOMA [ Time Frame: Week 0 and 16 ] [ Designated as safety issue: Yes ]
    fasting plasma glucose, insulin concentrations and HOMA-insulin resistance
  • 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 ]
Not Provided
Not Provided
 
Myocardial Function & FFA Metabolism in HIV Metabolic Syndrome
Myocardial Function, Free Fatty Acid and Glucose Metabolism in HIV Metabolic Syndrome

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
  • HIV Infections
  • Cardiovascular Disease
  • Insulin Resistance
  • HIV Lipodystrophy
  • The Metabolic Syndrome
  • Drug: Pioglitazone
    30mg/day for 16 weeks
    Other Name: Actos
  • Behavioral: Exercise Training
    Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
    Other Names:
    • Physical activity
    • Aerobic exercise
    • Weight lifting exercise
  • Active Comparator: Pioglitazone
    Pioglitazone (Actos, 30mg/day for 16 weeks)
    Intervention: Drug: Pioglitazone
  • Active Comparator: Exercise Training
    Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
    Intervention: Behavioral: Exercise Training

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
August 2010
August 2009   (final data collection date for primary outcome measure)

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.
Both
28 Years to 50 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00656851
DK59531 (completed), HRPO 05-0976
No
Kevin Yarasheski, Washington University School of Medicine
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Not Provided
Principal Investigator: Kevin Yarasheski, PhD Washington University School of Medicine
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP