Exercise and Pioglitazone for HIV-Metabolic Syndromes

NCT00639457 | Completed Results

• 2 other identifiers: DK 049393 (completed)WU 157
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infections; Type 2 Diabetes; Obesity; HIV; AIDS; Cardiovascular Disease; Lipodystrophy

Keywords

PPAR-gamma agonist; glucose metabolism; inflammation; adipose tissue distribution; cardiac function; vascular function; mass spectrometry; Treatment Experienced

Outcome Measures

Primary Outcomes (1)

• Insulin-stimulated Glucose Disposal Rate

  Insulin-mediated glucose disposal rate per kg of fat free mass per min

  Baseline and week16

Secondary Outcomes (14)

• Visceral Fat Volume

  Baseline and week 16

• Abdominal Subcutaneous Fat Volume

  Baseline and week 16

• Hepatic Lipid Content

  Baseline and week 16

• Hepatic Glucose Production Rate

  Baseline and week 16

• Serum Lipid and Lipoprotein Levels

  Baseline and week 16

Study Arms (2)

Pioglitazone

EXPERIMENTAL

Pioglitazone (Actos; 30mg/day) for 16 weeks.

Drug: Pioglitazone

Pioglitazone + Exercise training

ACTIVE COMPARATOR

Pioglitazone (Actos; 30mg/day) plus progressive aerobic and weight lifting exercise training (1.5hr/day x 3 days/wk)supervised and monitored by a personal exercise trainer.

Drug: Pioglitazone; Behavioral: Exercise training

Interventions

Pioglitazone DRUG

Oral 30mg/day for 16 weeks

Also known as: Actos

Pioglitazone; Pioglitazone + Exercise training

Exercise training BEHAVIORAL

Supervised aerobic and resistance exercise training (1.5hrs/day x 3 days/wk) for 16 weeks

Also known as: Physical activity

Pioglitazone + Exercise training

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• yr old HIV-infected men (n=40) and women (n=40).
• Source documentation of HIV status.
• Stable on highly active antiretroviral therapy (HAART) that may or may not include HIV-protease inhibitors for at least 3 months prior to enrollment. As of Jan 2005, HIV-infected long-term non-progressors will be included, even though they are not receiving HAART because it is likely that their disease status will not advance during the study period.
• Plasma HIV RNA (Roche Amplicor® assay) \<5000 copies/ml OR a CD4 T-cell count \>100 cells/µL and stable for previous 3 months.
• BMI 20-40kg/m2.
• "Normal" blood chemistries for at least 1 month prior to enrollment; platelet count \>30,000/mm3, absolute neutrophil count \<750/mm3, transaminases \<2.5x the upper limit of normal (ULN), creatinine \<3x ULN, fasting triglycerides \<500 mg/dL.

You may not qualify if:

• Medications or agents that might alter/impair glucose metabolism (insulin, glucocorticoids, corticosteroids, megace) during the 3 months prior to enrollment or at any time during enrollment. Volunteers who developed type 2 diabetes after HIV-infection or after starting anti-HIV medications, who are receiving insulin sensitizers (metformin, meglitinides, alpha-glucosidase inhibitors) or insulin secretagogues (sulfonylureas), but still do not have their blood sugars in control (defined as IGT above) are eligible.
• Abnormal or unstable (for 3 months prior to enrollment) endocrine blood chemistries that might otherwise explain insulin resistance. TSH \<0.2 or \>12µIU/mL, morning cortisol \>22µg/dL, IGF-1 \<115ng/mL, total testosterone \<200ng/dL (men) \<15ng/dL (women). Use of testosterone, ACTH, thyroid hormone, or rhGH replacement to normalize low levels is permitted, but must be stable on hormone replacement for 3 months prior to enrollment and will not discontinue this replacement during enrollment. Hormone replacement cannot be started during treatment.
• Allergy or hypersensitivity to thiazolidinediones. Currently taking a thiazolidinedione.
• Anti-obesity or anorectic medications during the 3 months prior to enrollment or at any time during enrollment. Lipid-lowering medications are permitted (fibrate or statin), but the subject must be stable on that agent for at least 3 months prior to enrollment. Lipid-lowering agents cannot be started during the treatment period.
• 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. This was revised in May 2006 to better clarify some uncertainties about hepatitis and eligibility.
• History of serious cardiovascular conditions or NY Heart Association (NYHA) cardiac status Class III or IV, (e.g., recent MI, unstable angina, edema, CHF, CAD, CABG, valve disease (murmur), stroke, uncontrolled high blood pressure (resting \>140/90 mmHg on 3 occasions), irregular heart rhythm, bundle-branch block, aortic stenosis, resting ST-segment depression \>1mm) that would preclude exercise testing/training, or substantially increase risk of a CV-event during exercise, or would limit the subjects ability to participate in exercise training. Treatment with medications for a cardiovascular condition (cardiac glycosides, alpha- or beta-blockers). Some antihypertensive medications (Ca++-channel blocker, diuretic, or ACE inhibitor) will be permitted.
• Insulin-dependent diabetes mellitus (IDDM) or a history of ketoacidosis, symptomatic diabetic neuropathy or retinopathy, or renal disease (creatinine \>3x ULN).
• Hematocrit \<34% in men or \<25% in women with symptoms (fatigue, "tired-legs", shortness of breath). Hemoglobin \<10 gm/100ml with symptoms.
• History of eating disorder, significant GI-disease
• Nausea, vomiting, diarrhea (\>4 loose stools/day) that are unresponsive to treatment during 2wks prior to enrollment or that persists for \>2wks during enrollment.
• Active secondary infection. Any significant change in chronic suppressive therapy for an opportunistic infection during the 1-month prior to enrollment.
• Unwilling or unable to do supervised exercise 3 sessions/wk at the Medical School exercise facility. Any condition that might be contraindicated for exercise training (disabling joint, cartilage or muscle injury/disorder that prohibits or severely limits participation in regular exercise, disabling arthritis, severe physical disabilities, claudication, pulmonary disease, sinus tachycardia, arrhythmias, premature atrial or ventricular contractions).
• Pregnancy or nursing mothers. Women cannot be pregnant and must agree to use an acceptable form of birth control during the treatment period. If birth control pills are used, the woman must be stable on these medications for at least 6 months prior to enrollment. All metabolic testing will be done in the early follicular phase. Urine pregnancy tests (hCG) will be done at baseline and every month the woman is enrolled in the study.
• Pancreatitis within prior 1 year. Serum triglycerides \>500mg/dL esp. with history of pancreatitis, or otherwise at high risk for pancreatitis.
• Medications that inhibit or slow blood coagulation (ie., blood thinners). Prothrombin (clotting) time exceeds 2 sec \> control (only in subjects who agree to muscle/fat biopsies).

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 (2)

• Reeds DN, Cade WT, Mondy K, Bopp C, Lassa-Claxton S, Yarasheski KE. Pioglitazone ± exercise training reduces liver lipid content and improves insulin sensitivity in HIV with impaired glucose tolerance (IGT). Antivir Ther. 12 Suppl 2: L14, 2007.

  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; Diabetes Mellitus, Type 2; Obesity; Acquired Immunodeficiency Syndrome; Cardiovascular Diseases; Lipodystrophy; Inflammation

Interventions

Pioglitazone; Exercise

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; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Slow Virus Diseases; Skin Diseases, Metabolic; Skin Diseases; Skin and Connective Tissue Diseases; Lipid Metabolism Disorders; Pathologic Processes

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

Limitations and Caveats

No intervention and exercise training only control groups were not included. Intracellular mechanisms were not explored. Relatively small number of participants taking a variety of anti-HIV medication regimens.

Results Point of Contact

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

key@wustl.edu

3143628173

Study Officials

• Kevin E 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: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: March 18, 2008
• First Posted: March 20, 2008
• Study Start: January 1, 2005
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2009
• Last Updated: October 23, 2013
• Results First Posted: September 12, 2013

Record last verified: 2013-09

Locations

US (1)