HIV InfectionsWU197NCT00656851
Myocardial Function & FFA Metabolism in HIV Metabolic Syndrome
A study testing Pioglitazone and Exercise Training in people with HIV Infections and Cardiovascular Disease, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
We hypothesize that the hearts of HIV+ people with The Metabolic Syndrome use and oxidize fats and sugars inappropriately, and that this may impair the heart's ability to pump blood. Read more about this study
- Who is it for?
- Ages 28 to 50 years
- Conditions the study is for
- HIV Infections, Cardiovascular Disease, Insulin Resistance
- What is being tested?
- Pioglitazone and Exercise Training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2005to Aug 2010
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 28 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
None listed.
Who cannot join
- Frank obesity (BMI >35kg/m2).
- 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.
- Diabetes [fasting glucose >125 mg/dL, or fasting insulin >45 µU/mL, or 2-hr glucose >200mg/dL].
- Medications or agents that regulate glucose metabolism (e.g., insulin-sensitizers, insulin-secretagogues). Lipid lowering agents that regulate lipid metabolism (i.e. fibrate, statin).
- Gestational diabetes, pregnancy, or nursing mothers.
- Serum triglycerides ≥ 500 mg/dL.
Show all 22Show fewer
- Hypogonadism [total testosterone <200ng/dL (men) or <15ng/dL (women)]; thyroid disorder [TSH <0.2 or >12µIU/mL]; hypercortisolemia [morning cortisol >22µg/dL]. Replacement testosterone or thyroid hormones to normalize abnormal levels is acceptable, as long as treatment and blood levels have been stable for at least 3 months.
- Use of human growth hormone (hGH) or GH-secretagogues (GH-releasing hormone-peptides) within the previous 3 months.
- History of serious cardiovascular disease; MI, angina pectoris, heart failure, congenital heart disease, coronary artery disease, coronary artery bypass graft, stroke. Bundle branch block is exclusionary because it limits the interpretability of the resting/exercise ECG. Cardiovascular or physical contraindications to maximal exercise testing on a cycle ergometer.
- Uncontrolled hypertension (>140/90 mmHg). Certain antihypertensive medications will be permitted (diuretics, ACE inhibitors) as long as the medication, dose, and blood pressure have been stable for at least 3 months.
- Well-trained athletes (defined as >3 exercise training exposures/week; >30min regimented exercise/exposure maintained for at least the prior 4 weeks).
- History of or active substance abuse (eg, alcoholism, cocaine, heroin, crack, methamphetamine, phencyclidine).
- Active secondary infection. Any significant change in chronic suppressive therapy for an opportunistic infection during 1 month prior to enrollment.
- New serious systemic infection during the 3 weeks prior to enrollment.
- History of hyperlactatemia or lactic acidosis, esp. with rapid weight loss.
- Debilitating-painful myopathy or neuropathy that requires 'assistance' to conduct normal activities of daily living (dressing, hygiene, preparing meals, operating a vehicle). These might affect peripheral substrate metabolism.
- Chronic renal insufficiency/failure or other comorbid conditions (eg. cancer, COPD) that alter metabolism.
- Pancreatitis, celiac disease, or cirrhosis.
- Inadequate macronutrient or energy intake, or malabsorptive disorder.
- Dementia or any condition that would prevent voluntary informed consent or compliance.
- Other compounds or blinded investigational new drugs that might affect metabolism or confound data interpretation (eg. RU486, interleukin therapy, or cytokine-receptor antagonist).
- Oral glucocorticoid or corticosteroid use within previous 3 months.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Myocardial Function, Free Fatty Acid and Glucose Metabolism in HIV Metabolic Syndrome
We hypothesize that the hearts of HIV+ people with The Metabolic Syndrome use and oxidize fats and sugars inappropriately, and that this may impair the heart's ability to pump blood. We hypothesize that exercise training or pioglitazone (Actos) will improve fat and sugar metabolism in the hearts of HIV+ people with The Metabolic Syndrome. This study will advance our understanding of cardiovascular disease in HIV+ people, and will test the efficacy of exercise training and pioglitazone for improving insulin resistance, heart metabolism and heart function in this at risk population.
Read the detailed description
We hypothesize that myocardial free fatty acid and glucose utilization and oxidation rates are dysregulated in HIV+ people with The Metabolic Syndrome in comparison to HIV+ people without The Metabolic Syndrome, and in comparison to HIV-seronegative people with and without The Metabolic Syndrome. We hypothesize that dysregulated myocardial fatty acid and glucose metabolism is associated with impaired heart function (diastolic dysfunction) in HIV+ people with The Metabolic Syndrome. We will use myocardial positron emission tomography, radioactive isotope tracers of palmitate and glucose, and echocardiography to evaluate myocardial metabolism and function. HIV+ people with The Metabolic Syndrome will receive 16wks of exercise training or pioglitazone (Actos), and we will evaluate their potential beneficial effects on myocardial metabolism and function.
- Conditions
- HIV Infections, Cardiovascular Disease, Insulin Resistance, HIV Lipodystrophy, The Metabolic Syndrome
- Being tested
- Pioglitazone, Exercise Training
- Keywords
- HIV/AIDS, Heart disease, Diabetes, Cardiovascular disease risk, Dyslipidemia, Visceral adiposity, treatment experienced
- Medical subject headings
- HIV Infections, Cardiovascular Diseases, Insulin Resistance, Acquired Immunodeficiency Syndrome, Heart Diseases, Diabetes Mellitus, Dyslipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called Actos
30mg/day for 16 weeks
Exercise TrainingBehavioural
Also called Physical activity, Aerobic exercise, Weight lifting exercise
Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone | Active comparator | Pioglitazone (Actos, 30mg/day for 16 weeks) Receives: Drug: Pioglitazone |
| Exercise Training | Active comparator | Cardiorespiratory and resistance exercise training 3days/wk for 16 weeks Receives: Behavioral: Exercise Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Myocardial Glucose Utilization Rate
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.
Measured: Weeks 0 and 16
Myocardial Glucose Utilization Rate Per Unit Insulin
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.
Measured: Weeks 0 and 16
Myocardial Fatty Acid Utilization Rate
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).
Measured: Weeks 0 and 16
Myocardial Fatty Acid Oxidation Rate
Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid oxidation rate.
Measured: Weeks 0 and 16
Myocardial Fatty Acid Esterification
Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid esterification as a % of total fatty acid extraction
Measured: Weeks 0 and 16
Secondary outcomes (4)
Myocardial Contractile Function During Diastole
Echocardiographic quantification of (E/A) early to late diastolic filling velocity. Aria transfer blood to the ventricles in 2 steps:
- 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.
- 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.
Measured: Weeks 0 and 16
Myocardial Contractile Function During Systole
Echocardiographic quantification of E' wall velocity during systole averaged at the lateral wall and septum
Measured: Weeks 0 and 16
Fasting Lipids and Lipoproteins
fasting serum triglycerides, LDL-, and HDL-cholesterol concentrations
Measured: Week 0 and 16
Fasting Glucose Insulin and HOMA
fasting plasma glucose, insulin concentrations and HOMA-insulin resistance
Measured: Week 0 and 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2008 (estimated)
- Study startSep 2005
- Primary completionAug 2009
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Kevin Yarasheski, Washington University School of Medicine
- Investigators
- Kevin Yarasheski, PhD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00656851
- Sponsor's protocol ID
- DK59531 (completed)
- Other IDs
- HRPO 05-0976
- Acronym
- WU197
- Status last verified
- Aug 2013
- First submitted
- 10 Apr 2008
- Last updated
- 28 Aug 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Cade WT, Reeds DN, Overton ET, Herrero P, Waggoner AD, Davila-Roman VG, Lassa-Claxton S, Gropler RJ, Soto PF, Krauss MJ, Yarasheski KE, Peterson LR. Effects of human immunodeficiency virus and metabolic complications on myocardial nutrient metabolism, blood flow, and oxygen consumption: a cross-sectional analysis. Cardiovasc Diabetol. 2011 Dec 8;10:111. doi: 10.1186/1475-2840-10-111.
PubMed 22151886Cade WT, Overton ET, Mondy K, de las Fuentes L, Davila-Roman VG, Waggoner AD, Reeds DN, Lassa-Claxton S, Krauss MJ, Peterson LR, Yarasheski KE. Relationships among HIV infection, metabolic risk factors, and left ventricular structure and function. AIDS Res Hum Retroviruses. 2013 Aug;29(8):1151-60. doi: 10.1089/AID.2012.0254. Epub 2013 May 6.
PubMed 23574474Yarasheski KE, Cade WT, Overton ET, Mondy KE, Hubert S, Laciny E, Bopp C, Lassa-Claxton S, Reeds DN. Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity. Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E243-51. doi: 10.1152/ajpendo.00468.2010. Epub 2010 Oct 19.
PubMed 20959530
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Myocardial Function, Free Fatty Acid and Glucose Metabolism in HIV Metabolic Syndrome
- ClinicalTrials.gov ID
- NCT00656851
- Acronym / sponsor ID
- WU197 / DK59531 (completed)
- Conditions
- HIV Infections, Cardiovascular Disease, Insulin Resistance, HIV Lipodystrophy, The Metabolic Syndrome
- Keywords
- HIV/AIDS, Heart disease, Diabetes, Cardiovascular disease risk, Dyslipidemia, Visceral adiposity, treatment experienced
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- Sep 2005
- Primary completion
- Aug 2009 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 11 Apr 2008 (estimated)
- Results
- Posted 20 Aug 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We hypothesize that the hearts of HIV+ people with The Metabolic Syndrome use and oxidize fats and sugars inappropriately, and that this may impair the heart's ability to pump blood. We hypothesize that exercise training or pioglitazone (Actos) will improve fat and sugar metabolism in the hearts of HIV+ people with The Metabolic Syndrome. This study will advance our understanding of cardiovascular disease in HIV+ people, and will test the efficacy of exercise training and pioglitazone for improving insulin resistance, heart metabolism and heart function in this at risk population.
Detailed description
We hypothesize that myocardial free fatty acid and glucose utilization and oxidation rates are dysregulated in HIV+ people with The Metabolic Syndrome in comparison to HIV+ people without The Metabolic Syndrome, and in comparison to HIV-seronegative people with and without The Metabolic Syndrome. We hypothesize that dysregulated myocardial fatty acid and glucose metabolism is associated with impaired heart function (diastolic dysfunction) in HIV+ people with The Metabolic Syndrome. We will use myocardial positron emission tomography, radioactive isotope tracers of palmitate and glucose, and echocardiography to evaluate myocardial metabolism and function. HIV+ people with The Metabolic Syndrome will receive 16wks of exercise training or pioglitazone (Actos), and we will evaluate their potential beneficial effects on myocardial metabolism and function.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone | Active comparator | Drug: PioglitazonePioglitazone (Actos, 30mg/day for 16 weeks) |
| Exercise Training | Active comparator | Behavioral: Exercise TrainingCardiorespiratory and resistance exercise training 3days/wk for 16 weeks |
Who may qualify
- Ages
- 28 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (22 listed)
- Frank obesity (BMI >35kg/m2).
- 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.
- Diabetes [fasting glucose >125 mg/dL, or fasting insulin >45 µU/mL, or 2-hr glucose >200mg/dL].
- Medications or agents that regulate glucose metabolism (e.g., insulin-sensitizers, insulin-secretagogues). Lipid lowering agents that regulate lipid metabolism (i.e. fibrate, statin).
- Gestational diabetes, pregnancy, or nursing mothers.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PioglitazoneAlso: Actos30mg/day for 16 weeks | Drug | Pioglitazone |
| Exercise TrainingAlso: Physical activity, Aerobic exercise, Weight lifting exerciseCardiorespiratory and resistance exercise training 3days/wk for 16 weeks | Behavioural | Exercise Training |
Primary outcome
Myocardial Glucose Utilization Rate
Time frame: 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.
Myocardial Glucose Utilization Rate Per Unit Insulin
Time frame: 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.
Myocardial Fatty Acid Utilization Rate
Time frame: 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).
Myocardial Fatty Acid Oxidation Rate
Time frame: Weeks 0 and 16
Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid oxidation rate.
Myocardial Fatty Acid Esterification
Time frame: 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
4 secondary outcomes
Myocardial Contractile Function During Diastole
Time frame: Weeks 0 and 16
Myocardial Contractile Function During Systole
Time frame: Weeks 0 and 16
Fasting Lipids and Lipoproteins
Time frame: Week 0 and 16
Fasting Glucose Insulin and HOMA
Time frame: Week 0 and 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22151886Cade WT, Reeds DN, Overton ET, Herrero P, Waggoner AD, Davila-Roman VG, Lassa-Claxton S, Gropler RJ, Soto PF, Krauss MJ, Yarasheski KE, Peterson LR. Effects of human immunodeficiency virus and metabolic complications on myocardial nutrient metabolism, blood flow, and oxygen consumption: a cross-sectional analysis. Cardiovasc Diabetol. 2011 Dec 8;10:111. doi: 10.1186/1475-2840-10-111.
- Results publication: PubMed 23574474Cade WT, Overton ET, Mondy K, de las Fuentes L, Davila-Roman VG, Waggoner AD, Reeds DN, Lassa-Claxton S, Krauss MJ, Peterson LR, Yarasheski KE. Relationships among HIV infection, metabolic risk factors, and left ventricular structure and function. AIDS Res Hum Retroviruses. 2013 Aug;29(8):1151-60. doi: 10.1089/AID.2012.0254. Epub 2013 May 6.
- Results publication: PubMed 20959530Yarasheski KE, Cade WT, Overton ET, Mondy KE, Hubert S, Laciny E, Bopp C, Lassa-Claxton S, Reeds DN. Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity. Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E243-51. doi: 10.1152/ajpendo.00468.2010. Epub 2010 Oct 19.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin Yarasheski, PhD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pioglitazone and Exercise Training in people with HIV Infections and Cardiovascular Disease, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Myocardial Glucose Utilization Rate (time frame: Weeks 0 and 16). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00656851, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2013.