Exercise and Pioglitazone for HIV-Metabolic Syndromes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kevin Yarasheski, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00639457
First received: March 18, 2008
Last updated: September 16, 2013
Last verified: September 2013
Results First Received: May 2, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: HIV Infections
Type 2 Diabetes
Obesity
HIV
AIDS
Cardiovascular Disease
Lipodystrophy
Interventions: Drug: Pioglitazone
Behavioral: Exercise training

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
HIV-infected men and women (18 – 60 yr old) were recruited from the AIDS Clinical Trials Unit, the Infectious Diseases Clinic, and the Volunteers for Health Program at Washington University School of Medicine, St. Louis MO between Jan 2005-Dec 2010. Participants were randomly assigned (1:1) to 4 mo of pioglitazone with or without exercise training.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Exclusion: AIDS diagnosis, non-compliant with anti-HIV medications, unstable CD4+ T-cell count or plasma HIV viremia, illegal drug abuse.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.

Participant Flow:   Overall Study
    Pioglitazone     Pioglitazone + Exercise Training  
STARTED     22     22  
COMPLETED     20     19  
NOT COMPLETED     2     3  
Withdrawal by Subject                 2                 3  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.
Total Total of all reporting groups

Baseline Measures
    Pioglitazone     Pioglitazone + Exercise Training     Total  
Number of Participants  
[units: participants]
  22     22     44  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     22     22     44  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  44  ± 2     46  ± 2     45  ± 2  
Gender  
[units: participants]
     
Female     3     2     5  
Male     19     20     39  
Region of Enrollment  
[units: participants]
     
United States     22     22     44  



  Outcome Measures
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1.  Primary:   Insulin-stimulated Glucose Disposal Rate   [ Time Frame: Baseline and week16 ]

Measure Type Primary
Measure Title Insulin-stimulated Glucose Disposal Rate
Measure Description Insulin-mediated glucose disposal rate per kg of fat free mass per min
Time Frame Baseline and week16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.

Measured Values
    Pioglitazone     Pioglitazone + Exercise Training  
Number of Participants Analyzed  
[units: participants]
  20     19  
Insulin-stimulated Glucose Disposal Rate  
[units: µmol glucose/kg FFM/min]
Mean ± Standard Error
   
Baseline     30  ± 4     34  ± 4  
Week 16     37  ± 6     48  ± 6  

No statistical analysis provided for Insulin-stimulated Glucose Disposal Rate



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

Measure Type Secondary
Measure Title Visceral Fat Volume
Measure Description No text entered.
Time Frame Baseline and week 16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.

Measured Values
    Pioglitazone     Pioglitazone + Exercise Training  
Number of Participants Analyzed  
[units: participants]
  20     19  
Visceral Fat Volume  
[units: cm3]
Mean ± Standard Error
   
Baseline     1933  ± 150     1890  ± 217  
Week 16     1970  ± 164     1746  ± 177  

No statistical analysis provided for Visceral Fat Volume



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

Measure Type Secondary
Measure Title Abdominal Subcutaneous Fat Volume
Measure Description No text entered.
Time Frame Baseline and week 16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.

Measured Values
    Pioglitazone     Pioglitazone + Exercise Training  
Number of Participants Analyzed  
[units: participants]
  20     19  
Abdominal Subcutaneous Fat Volume  
[units: cm3]
Mean ± Standard Error
   
Baseline     2101  ± 293     1877  ± 197  
Week 16     2164  ± 286     1905  ± 230  

No statistical analysis provided for Abdominal Subcutaneous Fat Volume



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

Measure Type Secondary
Measure Title Hepatic Lipid Content
Measure Description No text entered.
Time Frame Baseline and week 16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.

Measured Values
    Pioglitazone     Pioglitazone + Exercise Training  
Number of Participants Analyzed  
[units: participants]
  20     19  
Hepatic Lipid Content  
[units: percent of water]
Mean ± Standard Error
   
Baseline     12.1  ± 2.0     8.0  ± 1.7  
Week 16     10.7  ± 2.4     5.5  ± 0.8  

No statistical analysis provided for Hepatic Lipid Content



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

Measure Type Secondary
Measure Title Hepatic Glucose Production Rate
Measure Description ability of insulin to suppress hepatic glucose production = hepatic insulin sensitivity
Time Frame Baseline and week 16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.

Measured Values
    Pioglitazone     Pioglitazone + Exercise Training  
Number of Participants Analyzed  
[units: participants]
  20     19  
Hepatic Glucose Production Rate  
[units: percent suppression]
Mean ± Standard Error
   
Baseline     32  ± 3     37  ± 5  
Week 16     40  ± 6     42  ± 7  

No statistical analysis provided for Hepatic Glucose Production Rate



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

Measure Type Secondary
Measure Title Serum Lipid and Lipoprotein Levels
Measure Description No text entered.
Time Frame Baseline and week 16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.

Measured Values
    Pioglitazone     Pioglitazone + Exercise Training  
Number of Participants Analyzed  
[units: participants]
  20     19  
Serum Lipid and Lipoprotein Levels  
[units: mM/L]
Mean ± Standard Error
   
Baseline Triglycerides     2.3  ± 0.3     2.1  ± 0.4  
Week 16 Triglycerides     2.5  ± 0.3     1.8  ± 0.2  
Baseline Total Cholesterol     4.9  ± 0.2     4.7  ± 0.2  
Week 16 Total cholesterol     4.6  ± 0.2     4.5  ± 0.2  
Baseline LDL cholesterol     2.8  ± 0.2     2.7  ± 0.2  
Week 16 LDL cholesterol     2.5  ± 0.1     2.6  ± 0.2  
Baseline HDL cholesterol     0.99  ± 0.05     1.06  ± 0.05  
Week 16 HDL cholesterol     0.98  ± 0.05     1.09  ± 0.05  

No statistical analysis provided for Serum Lipid and Lipoprotein Levels



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

Measure Type Secondary
Measure Title Liver Enzyme Levels
Measure Description No text entered.
Time Frame Baseline and week 16  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.

Measured Values
    Pioglitazone     Pioglitazone + Exercise Training  
Number of Participants Analyzed  
[units: participants]
  20     19  
Liver Enzyme Levels  
[units: U/L]
Mean ± Standard Error
   
Baseline ALT     38  ± 7     34  ± 6  
Week 16 ALT     39  ± 8     32  ± 6  
Baseline AST     34  ± 7     27  ± 4  
Week 16 AST     30  ± 4     27  ± 3  

No statistical analysis provided for Liver Enzyme Levels



8.  Secondary:   Hemoglobin   [ Time Frame: Baseline and Week 16 ]

Measure Type Secondary
Measure Title Hemoglobin
Measure Description No text entered.
Time Frame Baseline and Week 16  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.

Measured Values
    Pioglitazone     Pioglitazone + Exercise Training  
Number of Participants Analyzed  
[units: participants]
  20     19  
Hemoglobin  
[units: g/L]
Mean ± Standard Error
   
Baseline Hemoglobin     13.8  ± 0.3     13.8  ± 0.5  
Week 16 Hemoglobin     13.7  ± 0.3     13.6  ± 0.4  

No statistical analysis provided for Hemoglobin



9.  Secondary:   Hematocrit   [ Time Frame: Baseline and Week 16 ]

Measure Type Secondary
Measure Title Hematocrit
Measure Description Percentage of blood volume that is red cells
Time Frame Baseline and Week 16  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.

Measured Values
    Pioglitazone     Pioglitazone + Exercise Training  
Number of Participants Analyzed  
[units: participants]
  20     19  
Hematocrit  
[units: % red cells]
Mean ± Standard Error
   
Baseline Hematocrit     39.9  ± 0.7     40.7  ± 1.4  
Week 16 Hematocrit     39.6  ± 0.7     39.7  ± 1.3  

No statistical analysis provided for Hematocrit



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

Measure Type Secondary
Measure Title Serum Adiponectin Levels
Measure Description No text entered.
Time Frame Baseline and week 16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.

Measured Values
    Pioglitazone     Pioglitazone + Exercise Training  
Number of Participants Analyzed  
[units: participants]
  20     19  
Serum Adiponectin Levels  
[units: µg/mL]
Mean ± Standard Error
   
Baseline serum adiponectin     4.7  ± 0.8     4.8  ± 0.8  
Week 16 serum adiponectin     7.0  ± 0.7     6.5  ± 0.9  

No statistical analysis provided for Serum Adiponectin Levels



11.  Secondary:   Myocardial Contractility   [ Time Frame: Baseline and week 16 ]

Measure Type Secondary
Measure Title Myocardial Contractility
Measure Description E/A ratio; ratio of the early (E) to late (A) ventricular filling velocities
Time Frame Baseline and week 16  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of participants for measures of myocardial contractility is less than that for all other measures. These measures were added to the protocol (after ~50% enrollment) after some reports suggested that this drug class (thiazolidinediones) may adversely affect heart function.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.

Measured Values
    Pioglitazone     Pioglitazone + Exercise Training  
Number of Participants Analyzed  
[units: participants]
  11     10  
Myocardial Contractility  
[units: ratio]
Mean ± Standard Error
   
Baseline E/A ratio     1.3  ± 0.2     1.2  ± 0.1  
Week 16 E/A ratio     1.4  ± 0.2     1.4  ± 0.1  

No statistical analysis provided for Myocardial Contractility



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

Measure Type Secondary
Measure Title Myocardial Contractility-LV Ejection Time
Measure Description Time required to empty the left ventricle into the aorta
Time Frame Baseline and week 16  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of participants for measures of myocardial contractility is less than that for all other measures. These measures were added to the protocol (after ~50% enrollment) after some reports suggested that this drug class (thiazolidinediones) may adversely affect heart function.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.

Measured Values
    Pioglitazone     Pioglitazone + Exercise Training  
Number of Participants Analyzed  
[units: participants]
  11     10  
Myocardial Contractility-LV Ejection Time  
[units: msec]
Mean ± Standard Error
   
Baseline LV ejection time     296  ± 8     281  ± 12  
Week 16 LV ejection time     294  ± 9     305  ± 9  

No statistical analysis provided for Myocardial Contractility-LV Ejection Time



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

Measure Type Secondary
Measure Title Myocardial Contractility-DT
Measure Description Deceleration time; time from the peak of early diastolic filling to baseline
Time Frame Baseline and week 16  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of participants for measures of myocardial contractility is less than that for all other measures. These measures were added to the protocol (after ~50% enrollment) after some reports suggested that this drug class (thiazolidinediones) may adversely affect heart function.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.

Measured Values
    Pioglitazone     Pioglitazone + Exercise Training  
Number of Participants Analyzed  
[units: participants]
  11     10  
Myocardial Contractility-DT  
[units: msec]
Mean ± Standard Error
   
Baseline DT     204  ± 7     214  ± 12  
Week 16 DT     193  ± 6     190  ± 4  

No statistical analysis provided for Myocardial Contractility-DT



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

Measure Type Secondary
Measure Title Myocardial Contractility-SBP
Measure Description Systolic blood pressure; peak vascular pressure during ventricular contraction
Time Frame Baseline and week 16  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of participants for measures of myocardial contractility is less than that for all other measures. These measures were added to the protocol (after ~50% enrollment) after some reports suggested that this drug class (thiazolidinediones) may adversely affect heart function.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.

Measured Values
    Pioglitazone     Pioglitazone + Exercise Training  
Number of Participants Analyzed  
[units: participants]
  11     10  
Myocardial Contractility-SBP  
[units: mmHg]
Mean ± Standard Error
   
Baseline SBP     114  ± 2     121  ± 4  
Week 16 SBP     114  ± 2     114  ± 3  

No statistical analysis provided for Myocardial Contractility-SBP



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

Measure Type Secondary
Measure Title Myocardial Contractility-DBP
Measure Description Diastolic blood pressure; vascular pressure during ventricular relaxation (diastole)
Time Frame Baseline and week 16  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of participants for measures of myocardial contractility is less than that for all other measures. These measures were added to the protocol (after ~50% enrollment) after some reports suggested that this drug class (thiazolidinediones) may adversely affect heart function.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos; 30mg/day) for 16 weeks.
Pioglitazone + Exercise Training 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.

Measured Values
    Pioglitazone     Pioglitazone + Exercise Training  
Number of Participants Analyzed  
[units: participants]
  11     10  
Myocardial Contractility-DBP  
[units: mmHg]
Mean ± Standard Error
   
Baseline DBP     65  ± 3     68  ± 5  
Week 16 DBP     67  ± 4     61  ± 4  

No statistical analysis provided for Myocardial Contractility-DBP




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Kevin Yarasheski, PhD
Organization: Washington Univ Med Sch
phone: 3143628173
e-mail: key@wustl.edu


Publications of Results:
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.


Responsible Party: Kevin Yarasheski, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00639457     History of Changes
Other Study ID Numbers: DK 049393 (completed), WU 157
Study First Received: March 18, 2008
Results First Received: May 2, 2013
Last Updated: September 16, 2013
Health Authority: United States: Federal Government