Myocardial Function & FFA Metabolism in HIV Metabolic Syndrome (WU197)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kevin Yarasheski, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00656851
First received: April 10, 2008
Last updated: August 19, 2013
Last verified: August 2013
Results First Received: April 30, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Diagnostic
Conditions: HIV Infections
Cardiovascular Disease
Insulin Resistance
HIV Lipodystrophy
The Metabolic Syndrome
Interventions: Drug: Pioglitazone
Behavioral: Exercise Training

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Twenty four participants were enrolled from the AIDS Clinical Trials Unit and Infectious Diseases Clinics at Washington University School of Medicine in St. Louis, Missouri, USA. This was a prospective, two-group, random assignment study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Exclusion criteria: medications or dietary supplements that affect metabolism (β-blocker, β-agonist, Ca2+ channel blocker, corticosteroid), neuromuscular disorder that affects metabolism or ability to exercise, consumed >3 alcohol drinks/wk, active Hep C or B, recreational-anabolic -appetite stimulant drugs, regular physical exercise.

Reporting Groups
  Description
Pioglitazone Pioglitazone (Actos, 30mg/day for 16 weeks)
Exercise Training Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks

Participant Flow:   Overall Study
    Pioglitazone     Exercise Training  
STARTED     12     12  
COMPLETED     12     8  
NOT COMPLETED     0     4  
Withdrawal by Subject                 0                 4  



  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)
Exercise Training Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
Total Total of all reporting groups

Baseline Measures
    Pioglitazone     Exercise Training     Total  
Number of Participants  
[units: participants]
  12     12     24  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     12     12     24  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  42  ± 7     41  ± 6     42  ± 6  
Gender  
[units: participants]
     
Female     3     0     3  
Male     9     12     21  
Region of Enrollment  
[units: participants]
     
United States     12     12     24  



  Outcome Measures
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1.  Primary:   Myocardial Glucose Utilization Rate   [ Time Frame: Weeks 0 and 16 ]

Measure Type Primary
Measure Title Myocardial Glucose Utilization Rate
Measure Description Radio-tracer (11C-glucose) and positron emission tomography quantification of myocardial glucose utilization rate. The rate at which glucose exits the blood, enters the muscle cells in the left ventricle, and is metabolized (ATP generation, glycolysis, glycogenolysis, or lactate production). Total glucose utilization rate in the left ventricle of the heart.
Time Frame Weeks 0 and 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)
Exercise Training Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks

Measured Values
    Pioglitazone     Exercise Training  
Number of Participants Analyzed  
[units: participants]
  12     8  
Myocardial Glucose Utilization Rate  
[units: (nmol glucose/g heart muscle/min]
Mean ± Standard Error
   
Week 0     109.6  ± 70.5     106.7  ± 69.0  
Week 16     109.1  ± 55.2     87.2  ± 97.4  

No statistical analysis provided for Myocardial Glucose Utilization Rate



2.  Primary:   Myocardial Glucose Utilization Rate Per Unit Insulin   [ Time Frame: Weeks 0 and 16 ]

Measure Type Primary
Measure Title Myocardial Glucose Utilization Rate Per Unit Insulin
Measure Description Radio-tracer (11C-glucose) and positron emission tomography quantification of myocardial glucose utilization rate per unit of plasma insulin. Total glucose utilization rate in the left ventricle of the heart expressed per unit of the circulating plasma insulin concentration.
Time Frame Weeks 0 and 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)
Exercise Training Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks

Measured Values
    Pioglitazone     Exercise Training  
Number of Participants Analyzed  
[units: participants]
  12     8  
Myocardial Glucose Utilization Rate Per Unit Insulin  
[units: (nmol glucose/g heart muscle/min/µU insu]
Mean ± Standard Error
   
Week 0     14.9  ± 22.1     11.9  ± 11.0  
Week 16     15.7  ± 12.4     21.7  ± 40.8  

No statistical analysis provided for Myocardial Glucose Utilization Rate Per Unit Insulin



3.  Primary:   Myocardial Fatty Acid Utilization Rate   [ Time Frame: Weeks 0 and 16 ]

Measure Type Primary
Measure Title Myocardial Fatty Acid Utilization Rate
Measure Description Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid utilization rate. The rate at which palmitate exits the blood, enters the muscle cells in the left ventricle, and is metabolized (oxidation, re-esterification).
Time Frame Weeks 0 and 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)
Exercise Training Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks

Measured Values
    Pioglitazone     Exercise Training  
Number of Participants Analyzed  
[units: participants]
  12     8  
Myocardial Fatty Acid Utilization Rate  
[units: (nmol palmitate/g heart muscle/min]
Mean ± Standard Error
   
Week 0     119.3  ± 39.8     119.8  ± 48.7  
Week 16     129.3  ± 34.5     130.4  ± 55.2  

No statistical analysis provided for Myocardial Fatty Acid Utilization Rate



4.  Primary:   Myocardial Fatty Acid Oxidation Rate   [ Time Frame: Weeks 0 and 16 ]

Measure Type Primary
Measure Title Myocardial Fatty Acid Oxidation Rate
Measure Description Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid oxidation rate.
Time Frame Weeks 0 and 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)
Exercise Training Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks

Measured Values
    Pioglitazone     Exercise Training  
Number of Participants Analyzed  
[units: participants]
  12     8  
Myocardial Fatty Acid Oxidation Rate  
[units: (nmol palmitate/g heart muscle/min]
Mean ± Standard Error
   
Week 0     92.4  ± 27.5     106.3  ± 49.6  
Week 16     110.1  ± 31.7     97.5  ± 36.6  

No statistical analysis provided for Myocardial Fatty Acid Oxidation Rate



5.  Primary:   Myocardial Fatty Acid Esterification   [ Time Frame: Weeks 0 and 16 ]

Measure Type Primary
Measure Title Myocardial Fatty Acid Esterification
Measure Description Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid esterification as a % of total fatty acid extraction
Time Frame Weeks 0 and 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)
Exercise Training Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks

Measured Values
    Pioglitazone     Exercise Training  
Number of Participants Analyzed  
[units: participants]
  12     8  
Myocardial Fatty Acid Esterification  
[units: (% of total fatty acid extraction)]
Mean ± Standard Error
   
Week 0     7  ± 7     4  ± 3  
Week 16     4  ± 5     7  ± 5  

No statistical analysis provided for Myocardial Fatty Acid Esterification



6.  Secondary:   Myocardial Contractile Function During Diastole   [ Time Frame: Weeks 0 and 16 ]

Measure Type Secondary
Measure Title Myocardial Contractile Function During Diastole
Measure Description

Echocardiographic quantification of (E/A) early to late diastolic filling velocity. Aria transfer blood to the ventricles in 2 steps:

  1. blood collected in the atria falls into the ventricles when the atrioventricular valves opens. In the left heart, the velocity at which the blood moves during this initial action is called the early or "E" filling velocity.
  2. residual blood in the atria, is emptied during diastole by atrial contraction. The velocity of the blood during atrial contraction is the "A" (for atrial) filling velocity. These are expressed as a ratio (E/A). If A exceeds E velocity (ratio <1.0) this is a clinical marker of diastolic dysfunction. This can occur when the left ventricular wall becomes so stiff as to impair proper filling, which can lead to diastolic heart failure.
Time Frame Weeks 0 and 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)
Exercise Training Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks

Measured Values
    Pioglitazone     Exercise Training  
Number of Participants Analyzed  
[units: participants]
  12     8  
Myocardial Contractile Function During Diastole  
[units: ratio]
Mean ± Standard Error
   
Week 0     1.4  ± 0.6     1.4  ± 0.3  
Week 16     1.4  ± 0.5     1.5  ± 0.2  

No statistical analysis provided for Myocardial Contractile Function During Diastole



7.  Secondary:   Myocardial Contractile Function During Systole   [ Time Frame: Weeks 0 and 16 ]

Measure Type Secondary
Measure Title Myocardial Contractile Function During Systole
Measure Description Echocardiographic quantification of E' wall velocity during systole averaged at the lateral wall and septum
Time Frame Weeks 0 and 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)
Exercise Training Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks

Measured Values
    Pioglitazone     Exercise Training  
Number of Participants Analyzed  
[units: participants]
  12     8  
Myocardial Contractile Function During Systole  
[units: cm/sec]
Mean ± Standard Error
   
Week 0     12.7  ± 1.8     13.1  ± 2.4  
Week 16     12.8  ± 1.6     13.6  ± 0.4  

No statistical analysis provided for Myocardial Contractile Function During Systole



8.  Secondary:   Fasting Lipids and Lipoproteins   [ Time Frame: Week 0 and 16 ]

Measure Type Secondary
Measure Title Fasting Lipids and Lipoproteins
Measure Description fasting serum triglycerides, LDL-, and HDL-cholesterol concentrations
Time Frame Week 0 and 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)
Exercise Training Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks

Measured Values
    Pioglitazone     Exercise Training  
Number of Participants Analyzed  
[units: participants]
  12     8  
Fasting Lipids and Lipoproteins  
[units: mg/dL]
Mean ± Standard Error
   
triglycerides wk 0     199  ± 119     185  ± 58  
triglycerides wk 16     182  ± 91     159  ± 33  
LDL-cholesterol wk 0     115  ± 36     112  ± 26  
LDL-cholesterol wk 16     97  ± 17     90  ± 24  
HDL-cholesterol wk 0     38.9  ± 11.0     38.1  ± 8.4  
HDL-cholesterol wk 16     38.8  ± 12.4     39.8  ± 21.8  

No statistical analysis provided for Fasting Lipids and Lipoproteins



9.  Secondary:   Fasting Glucose Insulin and HOMA   [ Time Frame: Week 0 and 16 ]

Measure Type Secondary
Measure Title Fasting Glucose Insulin and HOMA
Measure Description fasting plasma glucose, insulin concentrations and HOMA-insulin resistance
Time Frame Week 0 and 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)
Exercise Training Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks

Measured Values
    Pioglitazone     Exercise Training  
Number of Participants Analyzed  
[units: participants]
  12     8  
Fasting Glucose Insulin and HOMA  
[units: mg/dL µU/mL]
Mean ± Standard Error
   
glucose (mg/dL) wk 0     102  ± 15     91.9  ± 9.5  
glucose wk 16     95.3  ± 13     86.8  ± 8.2  
insulin (µU/mL) wk 0     20.5  ± 25.7     14.8  ± 8.4  
insulin wk 16     11.4  ± 9.6     11.8  ± 7.6  
HOMA-IR wk 0     6.1  ± 10.4     3.3  ± 1.7  
HOMA-IR wk 16     2.8  ± 2.7     2.6  ± 1.6  

No statistical analysis provided for Fasting Glucose Insulin and HOMA




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
We did not perform the myocardial metabolic measurements under insulin-stimulated conditions (i.e. hyperinsulinemic clamps). Small number of participants and high measurement variability, efficacy was not found. Study ended to minimize risk/benefit.


  More Information
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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:

Responsible Party: Kevin Yarasheski, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00656851     History of Changes
Other Study ID Numbers: DK59531 (completed), HRPO 05-0976
Study First Received: April 10, 2008
Results First Received: April 30, 2013
Last Updated: August 19, 2013
Health Authority: United States: Federal Government