Combination of Insulin Sensitizer and Leptin as Treatment for the HAART -Induced Metabolic Syndrome

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT00362440
• Date of registration: 09/08/2006
• Prospective Registration: No
• Primary sponsor: Beth Israel Deaconess Medical Center
• Public title: Combination of Insulin Sensitizer and Leptin as Treatment for the HAART -Induced Metabolic Syndrome
• Scientific title: A Combination of Insulin Sensitizer and Leptin as Treatment for the HAART -Induced Metabolic Syndrome: A Randomized, Double-blind, Placebo-controlled Clinical Trial
• Date of first enrolment: August 2006
• Target sample size: 9
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00362440
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Christos Mantzoros, MD
• Affiliation: Beth Israel Deaconess Medical Center

Key inclusion & exclusion criteria

Inclusion Criteria:

- Age18 years and above and ability and willingness to give written informed consent

- Documented HIV-1 infection

- At least 6 months of stable cumulative antiretroviral therapy with any available or
investigational anti- retroviral medication (protease inhibitor, nucleoside reverse
transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor, nucleotide
reverse transcriptase inhibitor)

- Lipoatrophy developed after initiating HAART treatment (see criteria below). Leptin
levels should be less than 4 ng/ml.

- Insulin resistance, impaired fasting glucose, impaired glucose tolerance or type 2
diabetes developed after starting the antiretroviral medications. These categories are
defined, respectively, as fasting insulin level above 15 µIU/ml; fasting serum glucose
value above 100 mg/dl; 2-hour serum glucose level during a 75 gram oral glucose
tolerance test (OGTT) between 140 and 200 mg/dl; and fasting glucose above 126 mg/dl
or random glucose level above 200 mg/dl with presence of the classic symptoms of
diabetes, such as polyuria, polydipsia, ketonuria, and rapid weight loss

- Hypertriglyceridemia and/or hypercholesterolemia developed after starting the
antiretroviral therapy. These categories are defined as fasting triglycerides greater
than 150 mg/dl and LDL cholesterol greater than 130 mg/dl, respectively

- Female subjects must have a negative urine pregnancy test before enrollment and must
agree to use a barrier contraception i.e. condoms, diaphragm or IUD, with or without a
hormonal-based method for the duration of the study. Women who are pregnant or become
pregnant during the study and who do not accept some form of contraception will be
excluded from the study.

- Patients should have history of peripheral fat wasting of the face (e.g. sunken
cheeks), limbs (including prominent veins), and/or buttocks, which developed after the
initiation of HAART therapy

- Patients should have physical exam findings of a) facial atrophy - sunken cheeks,
sunken temporal regions, and/or prominent temporal veins and b) wasting of fat in
periphery, limbs and/or buttocks (including prominent veins)

- Patients should have anthropometric measurements suggestive of decreased subcutaneous
fat content: Decreased triceps skinfold thickness (< 4 mm in men and < 8 mm in women)
or Decreased upper arm circumference (< 27.1 cm in men and < 23.3 cm in women) or
Decreased subscapular skinfold thickness (< 7 mm in men and < 7 mm in women) or dual
energy X-ray absorptiometry (DEXA) scanning suggestive of fat depletion: total body
fat < 14% in men and < 22% in women.

Exclusion Criteria:

- History of impaired glucose metabolism or hyperlipidemia prior to antiretroviral use

- Triglyceride levels higher than 1500 mg/dl after the 1 month run-in phase or anytime
during the study

- Abnormal hepatic function: liver function tests higher than twice the upper normal
range

- Abnormal renal function: creatinine higher than 1.3 mg/dl

- Any condition/illness that may affect study outcomes such as pregnancy, active
infection except HIV, clinically significant malabsorption/malnutrition, malignancy

- Any active hormonal disease and/or hormonal treatment that may affect the outcomes of
interest such as clinically overt hypo/hyperthyroidism, hypogonadism,
hypercortisolism, or treatment with steroids or growth hormone (exception: patients
taking testosterone can be included in the trial if they agree to continue the same
dosage for the duration of the trial)

- Present alcoholism or drug abuse. These conditions will be screened for by a detailed
history and systems review and baseline laboratory analysis with chemistries, CBC, and
hormone levels, and EKG.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

HIV Lipodystrophy

Intervention(s)

Drug: Pioglitazone or metformin

Drug: Leptin

Drug: Placebo

Primary Outcome(s)

Insulin Resistance (HOMA Index) [Time Frame: At the end of each 3 month intervention]

Secondary Outcome(s)

Cholesterol Levels [Time Frame: At the end of each 3 month intervention]

Body Composition (Fat Mass) [Time Frame: At the end of each 3 month intervention]

Secondary ID(s)

2005P000159

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

American Diabetes Association

Results

• Results available: Yes
• Date Posted: 23/03/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00362440