Myocardial Function & FFA Metabolism in HIV Metabolic Syndrome

NCT00656851 | Completed Results

• 2 other identifiers: DK59531 (completed)HRPO 05-0976
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infections; Cardiovascular Disease; Insulin Resistance; HIV Lipodystrophy; The Metabolic Syndrome

Keywords

HIV/AIDS; Heart disease; Diabetes; Cardiovascular disease risk; Dyslipidemia; Visceral adiposity; treatment experienced

Outcome Measures

Primary Outcomes (5)

• Myocardial Glucose Utilization Rate

  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.

  Weeks 0 and 16

• Myocardial Glucose Utilization Rate Per Unit Insulin

  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.

  Weeks 0 and 16

• Myocardial Fatty Acid Utilization Rate

  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).

  Weeks 0 and 16

• Myocardial Fatty Acid Oxidation Rate

  Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid oxidation rate.

  Weeks 0 and 16

• Myocardial Fatty Acid Esterification

  Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid esterification as a % of total fatty acid extraction

  Weeks 0 and 16

Secondary Outcomes (4)

• Myocardial Contractile Function During Diastole

  Weeks 0 and 16

• Myocardial Contractile Function During Systole

  Weeks 0 and 16

• Fasting Lipids and Lipoproteins

  Week 0 and 16

• Fasting Glucose Insulin and HOMA

  Week 0 and 16

Study Arms (2)

Pioglitazone

ACTIVE COMPARATOR

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

Drug: Pioglitazone

Exercise Training

ACTIVE COMPARATOR

Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks

Behavioral: Exercise Training

Interventions

Pioglitazone DRUG

30mg/day for 16 weeks

Also known as: Actos

Pioglitazone

Exercise Training BEHAVIORAL

Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks

Also known as: Physical activity, Aerobic exercise, Weight lifting exercise

Exercise Training

Eligibility Criteria

• Age: 28 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• years old.
• 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.
• 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).

You may not qualify if:

• 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 \[fasting glucose \>125 mg/dL, or fasting insulin \>45 µU/mL, or 2-hr glucose \>200mg/dL\].
• 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 \[TSH \<0.2 or \>12µIU/mL\]; 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.
• Use of human growth hormone (hGH) or GH-secretagogues (GH-releasing hormone-peptides) within the previous 3 months.
• 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.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (3)

• Cade WT, Reeds DN, Overton ET, Herrero P, Waggoner AD, Davila-Roman VG, Lassa-Claxton S, Gropler RJ, Soto PF, Krauss MJ, Yarasheski KE, Peterson LR. Effects of human immunodeficiency virus and metabolic complications on myocardial nutrient metabolism, blood flow, and oxygen consumption: a cross-sectional analysis. Cardiovasc Diabetol. 2011 Dec 8;10:111. doi: 10.1186/1475-2840-10-111.

  PMID: 22151886 RESULT

• Cade WT, Overton ET, Mondy K, de las Fuentes L, Davila-Roman VG, Waggoner AD, Reeds DN, Lassa-Claxton S, Krauss MJ, Peterson LR, Yarasheski KE. Relationships among HIV infection, metabolic risk factors, and left ventricular structure and function. AIDS Res Hum Retroviruses. 2013 Aug;29(8):1151-60. doi: 10.1089/AID.2012.0254. Epub 2013 May 6.

  PMID: 23574474 RESULT

• Yarasheski KE, Cade WT, Overton ET, Mondy KE, Hubert S, Laciny E, Bopp C, Lassa-Claxton S, Reeds DN. Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity. Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E243-51. doi: 10.1152/ajpendo.00468.2010. Epub 2010 Oct 19.

  PMID: 20959530 RESULT

MeSH Terms

Conditions

HIV Infections; Cardiovascular Diseases; Insulin Resistance; Acquired Immunodeficiency Syndrome; Heart Diseases; Diabetes Mellitus; Dyslipidemias

Interventions

Pioglitazone; Exercise; Resistance Training

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Slow Virus Diseases; Endocrine System Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human

Limitations and Caveats

We did not perform the myocardial metabolic measurements under insulin-stimulated conditions (i.e. hyperinsulinemic clamps). Small number of participants and high measurement variability, efficacy was not found. Study ended to minimize risk/benefit.

Results Point of Contact

• Title: Kevin Yarasheski, PhD
• Organization: Washington Univ Med Sch

key@wustl.edu

3143628173

Study Officials

• Kevin Yarasheski, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: April 10, 2008
• First Posted: April 11, 2008
• Study Start: September 1, 2005
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2010
• Last Updated: August 28, 2013
• Results First Posted: August 20, 2013

Record last verified: 2013-08

Locations

US (1)