Exercise and Pioglitazone for HIV-Metabolic Syndromes

2014-08-27 03:32:05 | BioPortfolio


The purpose is to examine the safety and efficacy of 16wks of pioglitazone (Actos; 30mg/d) with and without aerobic and strength exercise training for reducing glucose intolerance and central adiposity in HIV-infected people. We anticipate that pioglitazone + exercise training will improve glucose metabolism and insulin sensitivity, and reduce central adiposity more than pioglitazone alone. These improvements should translate into reduced cardiovascular disease risk in HIV-infected people.


Our prior research has examined the pathogenesis and potential treatments for metabolic complications in people living with HIV. We have adopted the "lipotoxicity" hypothesis for Metabolic Syndrome X to explain the pathogenesis of impaired glucose tolerance (IGT) and fat redistribution in HIV: increased lipolysis and mobilization of lipids and free fatty acids from subcutaneous adipose depots leads to their excessive deposition in muscle and liver which contributes to dyslipidemia, insulin resistance, increased hepatic glucose output, and possibly visceral fat accumulation. Effective treatments have not been identified. Consensus groups recommend regular exercise and dietary modifications as primary and pharmacologic interventions as secondary treatments for the syndromes. We propose to test the efficacy of aerobic and weight lifting exercise training and an oral insulin-sensitizing agent (pioglitazone) as treatments for HIV-associated IGT and fat redistribution. We propose a 4-month, 2-group randomized study to evaluate the efficacy of pioglitazone and exercise + pioglitazone in 40 men and 40 women living with HIV and IGT and fat redistribution. We will measure: insulin sensitivity, glucose disposal rate, hepatic glucose production rate (5hr-hyperinsulinemic euglycemic clamp with 6,6-[2H2]-glucose); whole-body and regional fat and muscle content (1H-MRI of the abdomen and thigh & DEXA), soleus muscle and liver lipid content (1H-MRS), muscle and fat PPARgamma/alpha mRNA and protein expression, serum lipid profiles, and serum adiponectin levels before and at the end of 4 months of treatment. We hypothesize that exercise training + pioglitazone will be more effective than pioglitazone alone at improving insulin sensitivity, reducing visceral fat, liver and muscle lipid content, and increasing peripheral subcutaneous fat content in HIV-infected people. We hypothesize that combined treatment will be more effective because exercise training will activate PPARalpha expression in muscle and pioglitazone will activate PPARy expression in fat and muscle. We anticipate that this project will provide direct evidence that supports the combined use of exercise training and pioglitazone in people living with HIV and experiencing metabolic and anthropomorphic disorders that increase cardiovascular disease risk.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


HIV Infections


Pioglitazone, Pioglitazone + exercise training


Washington University School of Medicine
St. Louis
United States


Active, not recruiting


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

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:32:05-0400

Clinical Trials [3832 Associated Clinical Trials listed on BioPortfolio]

Myocardial Function & FFA 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 h...

Observational Study to Assess Glycosylated Hemoglobin Changes After 6 Months of Treatment With Pioglitazone.

The purpose of this study is to asses changes in glycosylated hemoglobin, fasting blood lipids and genetic polymorphism's in peroxisomal proliferator activated receptors--gamma receptor af...

Efficacy and Safety of Alogliptin Combined With Pioglitazone in Treating Subjects With Type 2 Diabetes Mellitus.

The purpose of this study is to evaluate the safety and efficacy of alogliptin, once daily (QD), taken in combination with pioglitazone in adults with type 2 diabetes mellitus.

Pioglitazone and Serum Asymmetric Dimethylarginine (ADMA) in Patients With Diabetes

SPECIFIC AIMS 1. To determine whether pioglitazone will reduce levels of ADMA in patients with diabetes. 2. To determine whether nitric oxide products (NOx) are increased with piogli...

30 Week Parallel Group Comparison Study of Linagliptin + Pioglitazone (5+15, 5+30 and 5+45 mg) qd Versus Respective Monotherapies, Followed by a Comparison of 5mg+30mg and 5mg+45mg Versus Respective Monotherapies in Type 2 Diabetes for up to 54 Weeks

The primary objective is to demonstrate superior glycaemic control (HbA1c reduction) after 30 weeks of linagliptin/pioglitazone (5/15, 5/30 and 5/45 mg) versus the respective individual mo...

PubMed Articles [7869 Associated PubMed Articles listed on BioPortfolio]

Safety and efficacy of low dose pioglitazone compared with standard dose pioglitazone in type 2 diabetes with chronic kidney disease: A randomized controlled trial.

Choices of hypoglycemic agents for patients with type 2 diabetes and chronic kidney disease (CKD) are limited. Available data among patients with CKD suggest that pioglitazone was effective and safe, ...

The Pioglitazone Trek via Human PPAR Gamma: From Discovery to a Medicine at the FDA and Beyond.

For almost two decades, pioglitazone has been prescribed primarily to prevent and treat insulin resistance in some type 2 diabetic patients. In this review, we trace the path to discovery of pioglitaz...

Association Between Pioglitazone Use and Prostate Cancer: A Population-Based Case-Control Study in the Han Population.

To date, few epidemiologic studies have investigated the relationship between pioglitazone use and prostate cancer. The available studies show conflicting findings. This case-control study explored th...

Pioglitazone inhibits advanced glycation induced protein modifications and down-regulates expression of RAGE and NF-κB in renal cells.

The present work aims to determine the effect of pioglitazone on in-vitro albumin glycation and AGE-RAGE induced oxidative stress and inflammation. Bovine serum albumin was glycated by methylglyoxal i...

Pioglitazone Reduces Hepatocellular Carcinoma Development in Two Rodent Models of Cirrhosis.

Hepatocellular carcinoma (HCC) is one of the deadliest malignancies worldwide due to the lack of effective treatments. Chemoprevention in high-risk patients is a promising, alternative strategy. In th...

Medical and Biotech [MESH] Definitions

A cardiovascular exercise strategy with alternating short periods of intense anaerobic exercise with less-intense recovery periods.

A type of strength-building exercise program that requires the body muscle to exert a force against some form of resistance, such as weight, stretch bands, water, or immovable objects. Resistance exercise is a combination of static and dynamic contractions involving shortening and lengthening of skeletal muscles.

The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an EXERCISE TEST.

Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate.

Instructional programs in the care and development of the body, often in schools. The concept does not include prescribed exercises, which is EXERCISE THERAPY.

More From BioPortfolio on "Exercise and Pioglitazone for HIV-Metabolic Syndromes"

Quick Search


Relevant Topic

Cardiology is a specialty of internal medicine.  Cardiac electrophysiology : Study of the electrical properties and conduction diseases of the heart. Echocardiography : The use of ultrasound to study the mechanical function/physics of the h...

Searches Linking to this Trial