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

NCT00362440 | Completed Phase 2 Results

• 1 other identifier: 2005P000159
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether patients with HIV lipodystrophy (fat wasting) benefit from taking the combination of two drugs, one insulin sensitizer (either metformin or pioglitazone, both diabetes drugs) and leptin (a natural hormone produced by your fat cells). Our hope is that they will improve sugar and fat metabolism and positively affect the body fat changes you have noticed while taking HAART.

Conditions

HIV Lipodystrophy

Keywords

HIV lipodystrophy; Leptin; Fat wasting; Pioglitazone; Insulin resistance

Outcome Measures

Primary Outcomes (1)

• Insulin Resistance (HOMA Index)

  At the end of each 3 month intervention

Secondary Outcomes (2)

• Cholesterol Levels

  At the end of each 3 month intervention

• Body Composition (Fat Mass)

  At the end of each 3 month intervention

Study Arms (2)

Leptin

EXPERIMENTAL

Leptin replacement therapy

Drug: Leptin; Drug: Pioglitazone or metformin

Pioglitazone or metformin

PLACEBO COMPARATOR

Diabetes treatment therapy

Drug: Pioglitazone or metformin; Drug: Placebo

Interventions

Leptin DRUG

Leptin

Pioglitazone or metformin DRUG

Leptin; Pioglitazone or metformin

Placebo DRUG

Pioglitazone or metformin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• American Diabetes Association: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Lee JH, Chan JL, Sourlas E, Raptopoulos V, Mantzoros CS. Recombinant methionyl human leptin therapy in replacement doses improves insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy. J Clin Endocrinol Metab. 2006 Jul;91(7):2605-11. doi: 10.1210/jc.2005-1545. Epub 2006 Apr 24.

  PMID: 16636130 BACKGROUND

MeSH Terms

Conditions

Insulin Resistance

Interventions

Leptin; Pioglitazone; Metformin

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Adipokines; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines

Results Point of Contact

• Title: Dr. Christos Mantzoros
• Organization: BIDMC

cmantzor@bidmc.harvard.edu

617-667-8630

Study Officials

• Christos Mantzoros, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: August 9, 2006
• First Posted: August 10, 2006
• Study Start: August 1, 2006
• Primary Completion: May 1, 2011
• Study Completion: June 1, 2011
• Last Updated: March 23, 2017
• Results First Posted: March 23, 2017

Record last verified: 2017-02

Locations

US (1)