Trial Outcomes & Findings for Myocardial Function & FFA Metabolism in HIV Metabolic Syndrome (NCT NCT00656851)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

24 participants

Primary outcome timeframe

Weeks 0 and 16

Results posted on

2013-08-28

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Pioglitazone Pioglitazone (Actos, 30mg/day for 16 weeks)	Exercise Training Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
Overall Study STARTED	12	12
Overall Study COMPLETED	12	8
Overall Study NOT COMPLETED	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Pioglitazone Pioglitazone (Actos, 30mg/day for 16 weeks)	Exercise Training Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
Overall Study Withdrawal by Subject	0	4

Baseline Characteristics

Myocardial Function & FFA Metabolism in HIV Metabolic Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pioglitazone n=12 Participants Pioglitazone (Actos, 30mg/day for 16 weeks)	Exercise Training n=12 Participants Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks	Total n=24 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	42 years STANDARD_DEVIATION 7 • n=5 Participants	41 years STANDARD_DEVIATION 6 • n=7 Participants	42 years STANDARD_DEVIATION 6 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	12 participants n=7 Participants	24 participants n=5 Participants

PRIMARY outcome

Timeframe: Weeks 0 and 16

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.

Outcome measures

Outcome measures
Measure	Pioglitazone n=12 Participants Pioglitazone (Actos, 30mg/day for 16 weeks)	Exercise Training n=8 Participants Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
Myocardial Glucose Utilization Rate Week 16	109.1 (nmol glucose/g heart muscle/min Standard Error 55.2	87.2 (nmol glucose/g heart muscle/min Standard Error 97.4
Myocardial Glucose Utilization Rate Week 0	109.6 (nmol glucose/g heart muscle/min Standard Error 70.5	106.7 (nmol glucose/g heart muscle/min Standard Error 69.0

PRIMARY outcome

Timeframe: Weeks 0 and 16

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.

Outcome measures

Outcome measures
Measure	Pioglitazone n=12 Participants Pioglitazone (Actos, 30mg/day for 16 weeks)	Exercise Training n=8 Participants Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
Myocardial Glucose Utilization Rate Per Unit Insulin Week 0	14.9 (nmol glucose/g heart muscle/min/µU insu Standard Error 22.1	11.9 (nmol glucose/g heart muscle/min/µU insu Standard Error 11.0
Myocardial Glucose Utilization Rate Per Unit Insulin Week 16	15.7 (nmol glucose/g heart muscle/min/µU insu Standard Error 12.4	21.7 (nmol glucose/g heart muscle/min/µU insu Standard Error 40.8

PRIMARY outcome

Timeframe: Weeks 0 and 16

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).

Outcome measures

Outcome measures
Measure	Pioglitazone n=12 Participants Pioglitazone (Actos, 30mg/day for 16 weeks)	Exercise Training n=8 Participants Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
Myocardial Fatty Acid Utilization Rate Week 0	119.3 (nmol palmitate/g heart muscle/min Standard Error 39.8	119.8 (nmol palmitate/g heart muscle/min Standard Error 48.7
Myocardial Fatty Acid Utilization Rate Week 16	129.3 (nmol palmitate/g heart muscle/min Standard Error 34.5	130.4 (nmol palmitate/g heart muscle/min Standard Error 55.2

PRIMARY outcome

Timeframe: Weeks 0 and 16

Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid oxidation rate.

Outcome measures

Outcome measures
Measure	Pioglitazone n=12 Participants Pioglitazone (Actos, 30mg/day for 16 weeks)	Exercise Training n=8 Participants Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
Myocardial Fatty Acid Oxidation Rate Week 0	92.4 (nmol palmitate/g heart muscle/min Standard Error 27.5	106.3 (nmol palmitate/g heart muscle/min Standard Error 49.6
Myocardial Fatty Acid Oxidation Rate Week 16	110.1 (nmol palmitate/g heart muscle/min Standard Error 31.7	97.5 (nmol palmitate/g heart muscle/min Standard Error 36.6

PRIMARY outcome

Timeframe: Weeks 0 and 16

Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid esterification as a % of total fatty acid extraction

Outcome measures

Outcome measures
Measure	Pioglitazone n=12 Participants Pioglitazone (Actos, 30mg/day for 16 weeks)	Exercise Training n=8 Participants Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
Myocardial Fatty Acid Esterification Week 0	7 (% of total fatty acid extraction) Standard Error 7	4 (% of total fatty acid extraction) Standard Error 3
Myocardial Fatty Acid Esterification Week 16	4 (% of total fatty acid extraction) Standard Error 5	7 (% of total fatty acid extraction) Standard Error 5

SECONDARY outcome

Timeframe: Weeks 0 and 16

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.

Outcome measures

Outcome measures
Measure	Pioglitazone n=12 Participants Pioglitazone (Actos, 30mg/day for 16 weeks)	Exercise Training n=8 Participants Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
Myocardial Contractile Function During Diastole Week 0	1.4 ratio Standard Error 0.6	1.4 ratio Standard Error 0.3
Myocardial Contractile Function During Diastole Week 16	1.4 ratio Standard Error 0.5	1.5 ratio Standard Error 0.2

SECONDARY outcome

Timeframe: Weeks 0 and 16

Echocardiographic quantification of E' wall velocity during systole averaged at the lateral wall and septum

Outcome measures

Outcome measures
Measure	Pioglitazone n=12 Participants Pioglitazone (Actos, 30mg/day for 16 weeks)	Exercise Training n=8 Participants Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
Myocardial Contractile Function During Systole Week 0	12.7 cm/sec Standard Error 1.8	13.1 cm/sec Standard Error 2.4
Myocardial Contractile Function During Systole Week 16	12.8 cm/sec Standard Error 1.6	13.6 cm/sec Standard Error 0.4

SECONDARY outcome

Timeframe: Week 0 and 16

fasting serum triglycerides, LDL-, and HDL-cholesterol concentrations

Outcome measures

Outcome measures
Measure	Pioglitazone n=12 Participants Pioglitazone (Actos, 30mg/day for 16 weeks)	Exercise Training n=8 Participants Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
Fasting Lipids and Lipoproteins triglycerides wk 0	199 mg/dL Standard Error 119	185 mg/dL Standard Error 58
Fasting Lipids and Lipoproteins triglycerides wk 16	182 mg/dL Standard Error 91	159 mg/dL Standard Error 33
Fasting Lipids and Lipoproteins LDL-cholesterol wk 0	115 mg/dL Standard Error 36	112 mg/dL Standard Error 26
Fasting Lipids and Lipoproteins LDL-cholesterol wk 16	97 mg/dL Standard Error 17	90 mg/dL Standard Error 24
Fasting Lipids and Lipoproteins HDL-cholesterol wk 0	38.9 mg/dL Standard Error 11.0	38.1 mg/dL Standard Error 8.4
Fasting Lipids and Lipoproteins HDL-cholesterol wk 16	38.8 mg/dL Standard Error 12.4	39.8 mg/dL Standard Error 21.8

SECONDARY outcome

Timeframe: Week 0 and 16

fasting plasma glucose, insulin concentrations and HOMA-insulin resistance

Outcome measures

Outcome measures
Measure	Pioglitazone n=12 Participants Pioglitazone (Actos, 30mg/day for 16 weeks)	Exercise Training n=8 Participants Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
Fasting Glucose Insulin and HOMA glucose (mg/dL) wk 0	102 mg/dL µU/mL Standard Error 15	91.9 mg/dL µU/mL Standard Error 9.5
Fasting Glucose Insulin and HOMA glucose wk 16	95.3 mg/dL µU/mL Standard Error 13	86.8 mg/dL µU/mL Standard Error 8.2
Fasting Glucose Insulin and HOMA insulin (µU/mL) wk 0	20.5 mg/dL µU/mL Standard Error 25.7	14.8 mg/dL µU/mL Standard Error 8.4
Fasting Glucose Insulin and HOMA insulin wk 16	11.4 mg/dL µU/mL Standard Error 9.6	11.8 mg/dL µU/mL Standard Error 7.6
Fasting Glucose Insulin and HOMA HOMA-IR wk 0	6.1 mg/dL µU/mL Standard Error 10.4	3.3 mg/dL µU/mL Standard Error 1.7
Fasting Glucose Insulin and HOMA HOMA-IR wk 16	2.8 mg/dL µU/mL Standard Error 2.7	2.6 mg/dL µU/mL Standard Error 1.6

Adverse Events

Pioglitazone

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Exercise Training

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Kevin Yarasheski, PhD

Washington Univ Med Sch

Phone: 3143628173

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place