Lifestyle Modification and Metformin Use in the Treatment of HIV

NCT00399360 | Completed Results DMC

• 2 other identifiers: DK-49302-10ARR01DK049302
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infections; Metabolic Syndrome X

Keywords

HIV; Metabolic Syndrome; Lifestyle Modification; Metformin; Treatment Experienced

Outcome Measures

Primary Outcomes (6)

• Carotid Intima Media Thickness

  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.

  baseline and 12 months

• Waist Circumference

  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.

  baseline and 12 months

• High Density Lipoprotein (HDL)

  High density lipoprotein (HDL) was determined after an overnight fast. The change in HDL between baseline and 12 months is reported.

  baseline and 12 months

• Glucose

  Glucose level was determined after an overnight fast. The change in glucose between baseline and 12 months is reported.

  baseline and 12 months

• Systolic Blood Pressure

  Systolic blood pressure was measured after 5 minutes rest. The in systolic blood pressure between baseline and 12 months is reported.

  baseline and 12 months

• Coronary Artery Calcium Score

  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.

  baseline and 12 months

Secondary Outcomes (4)

• C-reactive Protein

  baseline and 12 months

• Abdominal Visceral Adiposity

  baseline and 12 months

• Cardiorespiratory Fitness

  baseline and 12 months

• Intramyocellular Lipid

  baseline and 12 months

Study Arms (4)

Group 1

PLACEBO COMPARATOR

No Lifestyle Modification and Placebo

Drug: Placebo

Group 2

ACTIVE COMPARATOR

Lifestyle Modification and Placebo

Drug: Placebo; Behavioral: Lifestyle Modification

Group 3

ACTIVE COMPARATOR

No Lifestyle Modification and Metformin

Drug: Metformin

Group 4

ACTIVE COMPARATOR

Lifestyle Modification and Metformin

Drug: Metformin; Behavioral: Lifestyle Modification

Interventions

Metformin DRUG

Starting at 500 mg twice daily and increasing to 850 mg twice daily after 3 Months

Group 3; Group 4

Placebo DRUG

500 mg twice daily increasing to 850 mg twice daily after 3 Months

Group 1; Group 2

Lifestyle Modification BEHAVIORAL

Lifestyle Modification

Group 2; Group 4

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Fitch K, Abbara S, Lee H, Stavrou E, Sacks R, Michel T, Hemphill L, Torriani M, Grinspoon S. Effects of lifestyle modification and metformin on atherosclerotic indices among HIV-infected patients with the metabolic syndrome. AIDS. 2012 Mar 13;26(5):587-97. doi: 10.1097/QAD.0b013e32834f33cc.

  PMID: 22112605 DERIVED

MeSH Terms

Conditions

HIV Infections; Metabolic Syndrome

Interventions

Metformin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

The study was relatively small and may have been underpowered to assess effect on secondary endpoints and to assess the effects of lifestyle modification. The sample size may have limited our ability to determine differences in dropout rates.

Results Point of Contact

• Title: Dr. Steven Grinspoon, Principal Investigator
• Organization: Massachusetts General Hospital

sgrinspoon@partners.org

617-726-3890

Study Officials

• Steven K. Grinspoon, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 13, 2006
• First Posted: November 14, 2006
• Study Start: December 1, 2006
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2012
• Last Updated: September 14, 2012
• Results First Posted: September 14, 2012

Record last verified: 2012-09

Locations

US (1)