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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 
Overall Participants Analyzed 
[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
  Hide All Outcome Measures

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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 ( Other Identifier: ACTU Washington University )
Study First Received: March 18, 2008
Results First Received: May 2, 2013
Last Updated: September 16, 2013
Health Authority: United States: Federal Government