Myocardial Function & FFA Metabolism in HIV Metabolic Syndrome

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Brief Title

Myocardial Function & FFA Metabolism in HIV Metabolic Syndrome

Official Title

Myocardial Function, Free Fatty Acid and Glucose Metabolism in HIV Metabolic Syndrome

Brief Summary

      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.
    

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.
    


Study Type

Interventional


Primary Outcome

Myocardial Glucose Utilization Rate

Secondary Outcome

 Myocardial Contractile Function During Diastole

Condition

HIV Infections

Intervention

Pioglitazone

Study Arms / Comparison Groups

 Pioglitazone
Description:  Pioglitazone (Actos, 30mg/day for 16 weeks)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

24

Start Date

September 2005

Completion Date

August 2010

Primary Completion Date

August 2009

Eligibility 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.
      

Gender

All

Ages

28 Years - 50 Years

Accepts Healthy Volunteers

No

Contacts

Kevin Yarasheski, PhD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00656851

Organization ID

DK59531 (completed)

Secondary IDs

HRPO 05-0976

Responsible Party

Principal Investigator

Study Sponsor

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


Study Sponsor

Kevin Yarasheski, PhD, Principal Investigator, Washington University School of Medicine


Verification Date

August 2013