Lifestyle Modification and Metformin Use in the Treatment of HIV
Condition: HIV Infections; Metabolic Syndrome X
MeSH terms: Metabolic Syndrome; Syndrome
Study type: Interventional

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.
    

Detailed description: 
      After two initial screening visits with medical and nutrition staff for informed consent and
      determination of eligibility qualifying subjects will be seen for a baseline visit.

      At baseline subjects will have an interval history and physical exam, lipodystrophy
      evaluation by investigator and patient report. Bloods will be taken for insulin, glucose,
      HgbA1c, lipid studies, creatinine, liver function, serum lactate, urine pregnancy (women),
      CD4, viral load, and complete blood count (CBC). Metabolic assessment will include a 2-hour
      oral glucose tolerance test and indirect calorimetry. Carotid ultrasound will be done for
      assessment of intima-media thickness. Body composition will be assessed by dual energy x-ray
      absorptiometry (DEXA), single-slice magnetic resonance imaging (MRI) scanning through the
      abdomen and mid thigh, magnetic resonance spectroscopy scanning to assess intramyocellular
      lipid of the calf, anthropometric measurements, and Cardiac computed tomography (CT) will be
      done.

      After the baseline visit, subjects will be randomized to 1 of 4 groups: 1) a lifestyle
      modification program plus metformin (also known as glucophage), 2) lifestyle modification
      plus placebo, 3) metformin alone or 4) placebo alone.

      The starting dose of metformin will be 500mg twice daily and this will increase to 850mg
      twice daily at the 3-month visit.

      An identical visit to that at baseline will be repeated at 12-months.

      Subjects will return at 1 month for an interval history and physical exam, assessment of
      compliance and side effects. Blood will be collected for CBC, lactate, liver function, and
      creatinine. Women will have a urine pregnancy.

      A 6-month visit will include an interval history and physical exam, assessment of compliance
      and side effects, 2 hour oral glucose tolerance test, fasting bloods (glucose, lipid panel,
      creatinine, liver function, serum lactate, CBC) will be done, a urine pregnancy will be
      checked in women. Carotid ultrasound will be done and body composition will be assessed by
      anthropometric measurements and DEXA scan.

      There will also be a short visit at 3 and 9 months to obtain an interval history and physical
      exam, safety labs (serum lactate, CBC, liver function, and creatinine), urine pregnancy
      (women). Subjects randomized to metformin or placebo will increase their dose from 500mg
      twice daily to 850mg twice daily at the 3 month visit.

      At each of the visits review of a 4 day food record will occur.

      Those randomized to lifestyle modification will attend weekly sessions with a study
      investigator to cover a "core-curriculum" that is modeled after the Diabetes Prevention
      Program (DPP) intervention. The primary goals of the lifestyle modification program are
      derived from a combination of recommendations from the American Academy of Clinical
      Endocrinologists (AACE) and National Cholesterol Education Program (NCEP). The goals are to
      eat less than or equal to 35% of total calories from fat (less than 7% from saturated fat, up
      to 10% from polyunsaturated fat with emphasis on sources of omega 3 fatty acids and reduction
      of trans fatty acids, up to 20% from monounsaturated fats), and 25-35g of fiber per day.

      The intensity of the counseling sessions will decrease in months 10 through 12 to biweekly
      counseling session with study investigators and biweekly phone contact, alternating.

      In addition to the program outlined above, those randomized to the lifestyle modification
      group will also participate in progressive resistance training. Each training session will
      begin with a 5 minute warm-up on a stationary bicycle at 50% of the estimated maximal heart
      rate (maximal heart rate=220-age). All sessions will be monitored by a licensed physical
      therapist. Immediately after the warm-up, a standard flexibility routine will be performed to
      minimize the risk of injury. Then, the aerobic training protocol will be performed. The
      aerobic training program will follow the general guidelines established by the American
      College of Sports Medicine. Training will be performed using a standard stationary bicycle.
      Aerobic/endurance exercise will be performed with large muscle groups. Each subject will
      complete three supervised training sessions per week for 12 months.

      Strength training will be performed using Keiser equipment. Selected muscle groups will be
      trained alternating upper and lower exercises in the following order: 1) hip extension, 2)
      lateral pull down, 3) knee extension, 4) elbow flexion, 5) knee flexion, and 6) chest press.
      Each repetition will include concentric and eccentric phases. Each muscle group will be
      trained individually 3 times per week, on alternate days. The subjects will perform three
      sets of 10 repetitions each for every muscle group, resting 2-3 seconds between repetitions,
      2 minutes between sets, and 4 minutes between muscle groups. The 1 repetition maximum will be
      measured every 3-4 weeks for the first 6 months and it will be repeated again at the 9 and 12
      month visits. The relative intensity will increase from 60-80% of the 1 repetition maximum
      over 6 months. Subjects not randomized to training will have a determination of 1 repetition
      maximum made at baseline, 6 and 12 months.
    

Intervention name(s): Metformin; Placebo; Lifestyle Modification
Intervention type(s): Drug; Drug; Behavioral
Intervention description(s): Starting at 500 mg twice daily and increasing to 850 mg twice daily after 3 Months; 500 mg twice daily increasing to 850 mg twice daily after 3 Months; Lifestyle Modification
Intervention MeSH terms: Metformin
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: HIV; Metabolic Syndrome; Lifestyle Modification; Metformin; Treatment Experienced