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Lifestyle Modification and Metformin Use in the Treatment of HIV

This study has been completed.
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Steven K. Grinspoon, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00399360
First received: November 13, 2006
Last updated: September 13, 2012
Last verified: September 2012
History of Changes
  Purpose

A healthy diet and exercise have improved the health of people without human immunodeficiency virus (HIV) who have Metabolic Syndrome. In this study we would like to find out if the same benefit can be seen in people with HIV and Metabolic Syndrome. Patients with Metabolic Syndrome usually have a large waist, high blood cholesterol levels, high blood pressure, and high blood sugar levels. These are risk factors, which may increase one's chance of developing heart disease and/or diabetes. The purpose of the study is to evaluate the effects of different methods of treating HIV associated Metabolic Syndrome. The groups are: 1) a lifestyle modification program plus metformin (also known as glucophage), 2) lifestyle modification plus placebo, 3) metformin alone or 4) placebo alone. The lifestyle modification program consists of nutrition and exercise sessions with the goal of improving body composition, heart health, and ways to lower the risk of developing diabetes.


Condition Intervention
HIV Infections
Metabolic Syndrome X
 Drug: Metformin
Drug: Placebo
Behavioral: Lifestyle Modification

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Strategies for the Treatment of HIV Associated Metabolic Syndrome

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Carotid Intima Media Thickness [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
    Carotid intima media thickness imaging of the common carotid artery was conducted using a high-resolution 7.5-MHz phased-array transducer (SONOS 2000/2500. The change of the carotid intima media thickness measurement between baseline and 12 months is reported.

  • Waist Circumference [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
    Iliac waist circumference measurements were obtained using an inelastic tape measure. All measurements were obtained in triplicate, with the patient undressed, and then averaged. The change of the waist circumference measurement between baseline and 12 months is reported.

  • High Density Lipoprotein (HDL) [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
    High density lipoprotein (HDL) was determined after an overnight fast. The change in HDL between baseline and 12 months is reported.

  • Glucose [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
    Glucose level was determined after an overnight fast. The change in glucose between baseline and 12 months is reported.

  • Systolic Blood Pressure [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
    Systolic blood pressure was measured after 5 minutes rest. The in systolic blood pressure between baseline and 12 months is reported.

  • Coronary Artery Calcium Score [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
    Computed tomography (CT) imaging was performed using a SOMATOM Sensation (Siemens Medical Solutions, Forcheim, Germany) 64-slice CT scanner. Agatston calcium score was calculated using CT images. The total Agatston score is calculated by summing up the scores of the individual calcifications in all slices of the CT scan. An absolute Agatston score of less than 10 indicates minimal overall atherosclerosis (plaques) in the coronary arteries. The change in the coronary artery calcium score between baseline and 12 months is reported.


Secondary Outcome Measures:
  • C-reactive Protein [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
    High sensitivity C-reactive protein was determined by R&D Systems (Minneapolis, MN) kit. The change in C-reactive protein between baseline and 12 months is reported.

  • Abdominal Visceral Adiposity [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
    Abdominal visceral adipose area was assess by magnetic resonance imaging at the lvel of the L4 pedicle. The change in abdominal visceral adiposity between baseline and 12 months is reported.

  • Cardiorespiratory Fitness [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
    A submaximal exercise stress test was conducted on a cycle ergometer to measure endurance. Subjects cycled between 50-60 revolutions per minute and the workload was progressively increased in increments of 50 watts in stages lasting 3 minutes. Once subjects became fatigued or reached their submaximal heart rate (220-age x 85), the test was stopped and separate readings of heart rate and blood pressure were measured at 1, 3, and 5 min of recovery. Weight-adjusted maximum oxygen consumption (VO2max; ml/kg per minute) was determined. The change in cardiorespiratory fitness between baseline and 12 months is reported.

  • Intramyocellular Lipid [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
    Intramyocellular lipid (IMCL) of the tibialis anterior was determined using 1H-magnetic resonance spectroscopy (Siemens, Munich, Germany). The change in the intramyocellular lipid measurement between baseline and 12 months is reported.


Enrollment: 50
Study Start Date: December 2006
Study Completion Date: June 2012
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Group 1
No Lifestyle Modification and Placebo
 Drug: Placebo
500 mg twice daily increasing to 850 mg twice daily after 3 Months
Active Comparator: Group 2
Lifestyle Modification and Placebo
 Drug: Placebo
500 mg twice daily increasing to 850 mg twice daily after 3 Months
Behavioral: Lifestyle Modification
Lifestyle Modification
Active Comparator: Group 3
No Lifestyle Modification and Metformin
 Drug: Metformin
Starting at 500 mg twice daily and increasing to 850 mg twice daily after 3 Months
Active Comparator: Group 4
Lifestyle Modification and Metformin
 Drug: Metformin
Starting at 500 mg twice daily and increasing to 850 mg twice daily after 3 Months
Behavioral: Lifestyle Modification
Lifestyle Modification

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 and ≤ 65 years of age
  • HIV positive, on a stable combination antiretroviral regimen for > 6 months, including but not limited to either 2 nucleoside reverse transcriptase inhibitors (NRTI) and a non-nucleoside reverse transcriptase inhibitors (NNRTI) or protease inhibitor (PI), or a triple NRTI regimen
  • Ability and motivation to modify behavior and make lifestyle changes
  • NCEP-Adult Treatment Panel III defined metabolic syndrome, as defined by 3 out of 5 of the following: 1) Waist circumference greater than 102 cm (40 in) in men and 88 cm (35 in) in women, 2) Triglycerides ≥ 150 mg/dL or current anti-lipolytic drug treatment, 3) high-density lipoprotein less than 40mg/dL in men and 50 mg/dL in women, 4) Blood pressure ≥ 130/85 mmHg or current antihypertensive drug treatment, 5) Fasting glucose ≥ 100 mg/dL

Exclusion Criteria:

  • Any new serious opportunistic infection within the past 6 weeks
  • History of unstable angina, aortic stenosis, uncontrolled hypertension, severe neuropathy, arthritis or other contraindication to exercise
  • Current therapy with insulin or other diabetic agent, fasting blood sugar > 126
  • Requiring parenteral nutrition or parenteral glucocorticoid therapy or oral glucocorticoid therapy
  • Estrogen, progestational derivative, or ketoconazole use within 3 months
  • New antiretroviral regimen in the past 6 months
  • Serum creatinine > 1.5 mg/dL (males) and 1.4 mg/dL (females), serum glutamic pyruvic transaminase-liver function (SGPT), > 2.5 upper limit of normal (ULN), Lactate > 2.0 ULN, hemoglobin < 10.0 mg/dL
  • Current substance and/or alcohol abuse
  • Known hypersensitivity to Metformin
  • Congestive heart failure requiring pharmacologic treatment
  • Use of cimetidine or planned use during the study period
  • Hypertrophic obstructive cardiomyopathy
  • Pregnant or actively seeking pregnancy, breastfeeding
  • Testosterone use for non-physiologic purposes, or physiologic testosterone replacement for < 3 months.
  • Presence of active AIDS including cancers
  • Current viral, bacterial or other infections (excluding HIV)
  • Weight loss in the past 3 months of greater than 10 pounds
  • Nitrates or other medications that can alter endothelial function
  • Contraindication to beta blocker or nitroglycerin use
  • Patients with previous allergic reactions to iodine-containing contrast media or to iodine
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00399360

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Steven K. Grinspoon, MD Massachusetts General Hospital
  More Information

No publications provided by Massachusetts General Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Steven K. Grinspoon, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00399360     History of Changes
Other Study ID Numbers: DK-49302-10AR, R01DK049302
Study First Received: November 13, 2006
Results First Received: May 18, 2012
Last Updated: September 13, 2012
Health Authority: United States: Federal Government

Keywords provided by Massachusetts General Hospital:
HIV
Metabolic Syndrome
Lifestyle Modification
Metformin
Treatment Experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Metabolic Syndrome X
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
 Immune System Diseases
Slow Virus Diseases
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on March 07, 2013