HIV Infections Clinical Research Study

What is the purpose of this study?

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.

Can I participate in this study?

You may be eligible for this study if you meet the following criteria:

• Conditions: HIV Infections, Cardiovascular Disease, Insulin Resistance, HIV Lipodystrophy, The Metabolic Syndrome
• Age: Between 28 - 50 Years
• Gender: Male or Female
• +

  Inclusion Criteria:

  28-50 years old.

  Plasma HIV RNA less than 5 000 copies/mL for previous 3 months OR CD4 count greater

  than 100 cells/?L for previous 3 months.

  Stable for at least the past 3 months on any HAART regimen.

  "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:

  Frank obesity (BMI >35kg/m2).

  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.

  Diabetes [fasting glucose >125 mg/dL or fasting insulin >45 ?U/mL or 2-hr glucose

  >200mg/dL].

  Medications or agents that regulate glucose metabolism (e.g. insulin-sensitizers

  insulin-secretagogues). Lipid lowering agents that regulate lipid metabolism (i.e.

  fibrate statin).

  Gestational diabetes pregnancy or nursing mothers.

  Serum triglycerides ? 500 mg/dL.

  Hypogonadism [total testosterone <200ng/dL (men) or <15ng/dL (women)]; thyroid

  disorder [TSH <0.2 or >12?IU/mL]; hypercortisolemia [morning cortisol >22?g/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.

  Use of human growth hormone (hGH) or GH-secretagogues (GH-releasing hormone-peptides)

  within the previous 3 months.

  History of serious cardiovascular disease; MI angina pectoris heart failure

  congenital heart disease coronary artery disease coronary artery bypass graft

  the resting/exercise ECG. Cardiovascular or physical contraindications to maximal

  exercise testing on a cycle ergometer.

  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.

  Well-trained athletes (defined as >3 exercise training exposures/week; >30min

  regimented exercise/exposure maintained for at least the prior 4 weeks).

  History of or active substance abuse (eg alcoholism cocaine heroin crack

  methamphetamine phencyclidine).

  Active secondary infection. Any significant change in chronic suppressive therapy for

  an opportunistic infection during 1 month prior to enrollment.

  New serious systemic infection during the 3 weeks prior to enrollment.

  History of hyperlactatemia or lactic acidosis esp. with rapid weight loss.

  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.

  Chronic renal insufficiency/failure or other comorbid conditions (eg. cancer COPD)

  that alter metabolism.

  Pancreatitis celiac disease or cirrhosis.

  Inadequate macronutrient or energy intake or malabsorptive disorder.

  Dementia or any condition that would prevent voluntary informed consent or

  compliance.

  Other compounds or blinded investigational new drugs that might affect metabolism or

  confound data interpretation (eg. RU486 interleukin therapy or cytokine-receptor

  antagonist).

  Oral glucocorticoid or corticosteroid use within previous 3 months.

Detail Study 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 Treatments

Pioglitazone, Exercise training

Last Updated: October 2009