Exercise and Pioglitazone for HIV-Metabolic Syndromes

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00639457
• Date of registration: 18/03/2008
• Prospective Registration: No
• Primary sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Public title: Exercise and Pioglitazone for HIV-Metabolic Syndromes
• Scientific title: Exercise and Pioglitazone for HIV-Metabolic Syndromes
• Date of first enrolment: January 2005
• Target sample size: 44
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00639457
• Study type: Interventional
• Phase: N/A

Countries of recruitment

United States

Contacts

• Name: Kevin E Yarasheski, PhD
• Affiliation: Washington University School of Medicine

Key inclusion & exclusion criteria

Inclusion Criteria:

1. 18-65 yr old HIV-infected men (n=40) and women (n=40).

2. Source documentation of HIV status.

3. 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.

4. Impaired glucose tolerance (IGT) or type 2 diabetes and fat redistribution. IGT is
defined as: fasting (8hr) plasma glucose 100-126mg/dL or plasma glucose >140 mg/dL
2-hours after a 75g-oral glucose load. This definition (proposed/revised May 2006)
includes volunteers with adult onset type 2 diabetes (non-insulin dependent diabetes),
because we believe that these volunteers may benefit from the potential
glucose-lowering actions of pioglitazone with or without exercise training. Fat
redistribution is defined as any 2 of the following: waist-to-hip ratio >0.85 women or
>0.95 men, or trunk/appendicular adipose ratio using whole-body DEXA >0.85 women or
>1.3 men, or <15% leg fat (DEXA; (leg fat/total body fat) x100), or visceral adiposity
VAT >120 cm2 women or >140 cm2 men, or a VAT/TAT ratio >0.30 women or >0.40 men.
Overall, the eligibility criteria are designed to include subjects with metabolic
syndromes that increase CVD risk, and the potential to gain the greatest benefit from
pioglitazone and exercise training. These inclusion criteria will help select/maintain
homogeneous groups of study participants.

5. Plasma HIV RNA (Roche Amplicor® assay) <5000 copies/ml OR a CD4 T-cell count >100
cells/µL and stable for previous 3 months.

6. BMI 20-40kg/m2.

7. "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.

Exclusion Criteria:

1. 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.

2. 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.

3. Allergy or hypersensitivity to thiazolidinediones. Currently taking a
thiazolidinedione.

4. 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.

5. 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.

6. 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.

7. Insulin-dependent diabetes mellitus (IDDM) or a history of ketoacidosis, symptomatic
diabetic neuropathy or retinopathy, or renal disease (creatinine >3x ULN).

8. Hematocrit <34% in men or <25% in women with symptoms (fatigue, "tired-legs",
shortness of breath). Hemoglobin <10 gm/100ml with symptoms.

9. History of eating disorder, significant GI-disease

10. Nausea, vomiting, diarrhea (>4 loose stools/day) that are unresponsive to treatment
during 2wks prior to enrollment or that persists for >2wks during enrollment.

11. Active secondary infection. Any significant change in chronic suppressive therapy for
an opportunistic infection during the 1-month prior to enrollment.

12. During the 3 months prior to enrollment, regular aerobic or weight lifting exercise
training that exceeds the minimum (45min/d, 3d/wk, >75% exercise capacity) required
for the metabolic, biochemical, and anthropomorphic benefits of exercise to be
attained as described in the American College of Sports Medicine Guidelines. In Apr
2006, this exclusion criterion was modified in order to facilitate enrollment of
volunteers who are moderately-highly active during the 3months prior to screening for
this study. We will randomize volunteers who exercise regularly into the two treatment
groups. This will reduce the potential confounding effects of regular exercise on the
metabolic, biochemical, and anthropomorphic benefits of exercise training that is
prescribed during the treatment phase. We have excluded several volunteers who are
regular exercisers, and we believe we may be unnecessarily excluding them. They can be
included, enrollment will be facilitated, and the study design will not be adversely
affected, as long as we randomize them into pioglitazone or exercise+pioglitazone
(1:1).

13. Unwilling or unable to do supervised exercise 3 sessions/wk at the Medical School
exercise facility. Any condition that might be contrain


Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Cardiovascular Disease

AIDS

HIV Infections

Lipodystrophy

Obesity

Type 2 Diabetes

HIV

Intervention(s)

Drug: Pioglitazone

Behavioral: Exercise training

Primary Outcome(s)

Insulin-stimulated Glucose Disposal Rate [Time Frame: Baseline and week16]

Secondary Outcome(s)

Hematocrit [Time Frame: Baseline and Week 16]

Myocardial Contractility-LV Ejection Time [Time Frame: Baseline and week 16]

Myocardial Contractility-SBP [Time Frame: Baseline and week 16]

Abdominal Subcutaneous Fat Volume [Time Frame: Baseline and week 16]

Hepatic Glucose Production Rate [Time Frame: Baseline and week 16]

Visceral Fat Volume [Time Frame: Baseline and week 16]

Hepatic Lipid Content [Time Frame: Baseline and week 16]

Serum Lipid and Lipoprotein Levels [Time Frame: Baseline and week 16]

Myocardial Contractility-DBP [Time Frame: Baseline and week 16]

Hemoglobin [Time Frame: Baseline and Week 16]

Myocardial Contractility [Time Frame: Baseline and week 16]

Myocardial Contractility-DT [Time Frame: Baseline and week 16]

Liver Enzyme Levels [Time Frame: Baseline and week 16]

Serum Adiponectin Levels [Time Frame: Baseline and week 16]

Secondary ID(s)

WU 157

DK 049393 (completed)

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 12/09/2013
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00639457