Clinical trial NCT00123253: TH9507 in Patients With HIV-Associated Lipodystrophy
Official title: A Phase 3 Multicenter, Double-Blind, Randomized, Placebo-Controlled Study Assessing the Efficacy and Safety of a 2 mg Dose of TH9507, a Growth Hormone Releasing Factor Analog, in HIV Patients With Excess of Abdominal Fat Accumulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Lipodystrophy
Keywords: HIV
Lipodystrophy
Abdominal fat accumulation
Growth hormone releasing factor/Growth hormone releasing hormone
Treatment Experienced
Lead sponsor: Theratechnologies
Sponsor class: INDUSTRY
First posted: 2005-07-22
Enrollment: 412
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: HIV lipodystrophy affects a significant proportion of patients treated with combination antiretroviral therapy (ART) and is characterized by excess visceral fat accumulation and loss of extremity and subcutaneous fat, in association with dyslipidemia and insulin resistance. Data from a previous randomized, placebo-controlled trial demonstrated that daily administration of 2mg TH9507, a growth hormone releasing factor (GRF), to HIV patients with an excess of abdominal fat accumulation for 12 weeks resulted in decreases in visceral adipose tissue (VAT) and trunk fat, with no significant changes in limb fat and subcutaneous adipose tissue (SAT). This study is aimed at further assessing the efficacy and safety of 2 mg TH9507 in a larger population of HIV patients treated with ART and experiencing an excess of abdominal fat accumulation.


Eligibility criteria: Inclusion Criteria:

* Ages 18 to 65 years inclusive
* HIV positive; CD4 cell counts \>100 cells/mm3; viral load \<10,000 copies/mL (stable for 8 weeks)
* On stable ART regimen for at least 8 weeks prior to randomization
* Have evidence of abdominal fat accumulation defined by the following anthropometric cut off values:

  * For males: waist circumference \> 95 cm and waist to hip ratio \> 0.94;
  * For females: waist circumference \> 94 cm and waist to hip ratio \> 0.88.
* Females of childbearing potential not pregnant or lactating; normal mammography within 6 months of study.
* Signed informed consent

Exclusion Criteria:

* Body mass index \< 20 kg/m2
* Opportunistic infection; HIV-related disease within 3 months of study.
* History of malignancy; active neoplasm.
* Prostate-specific antigen (PSA) \>5 ng/mL at screening
* Hypopituitarism; history of pituitary tumor/surgery; head irradiation; head trauma that has affected the somatotropic axis.
* Untreated hypothyroidism
* Type 1 diabetics and type 2 diabetics on oral hypoglycemic or insulin sensitizing agent within 6 months of study
* ALT or AST \> 3 x ULN; serum creatinine \> 133 mmol/L (1.5 mg/dL); hemoglobin more than 20 g/L below LLN; fasting blood glucose \> 8.33 mmol/L (150 mg/dL); fasting triglycerides \> 11.3 mmol/L (0.99 g/dL).
* Untreated hypertension
* Change in anti-hyperlipemic regimen within 3 months prior to study
* Change in testosterone regimen and/or supraphysiological dose of testosterone
* Estrogen therapy
* Anoretics/anorexigenics or anti-obesity agents within 3 months of study
* Growth hormone (GH); GH secretagogues; growth hormone releasing factor (GRF) products; IGF-1; or IGFBP-3 within 6 months of study.
* Drug or alcohol dependence or use of methadone within 6 months of study entry
* Participation in a clinical trial with any investigational drug/device within 30 days of screening.

Primary outcomes:
measure: Visceral adipose tissue (VAT)
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA School of Medicine
state: California
city: Palm Springs
country: United States
facility: Office of Dr. Michael Somero
state: California
city: San Diego
country: United States
facility: UCSD Medical Center
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente
state: California
city: West Hollywood
country: United States
facility: AIDS Research Alliance
state: California
city: Washington
country: United States
facility: Capital Medical Associates
state: District of Columbia
city: Bradenton
country: United States
facility: Bach & Godofsky
state: Florida
city: Ft. Lauderdale
country: United States
facility: Office of Dr. Gary Richmond
state: Florida
city: Miami
country: United States
facility: Care Resource Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Sarasota
country: United States
facility: Infectious Disease Associates
state: Florida
city: Vero Beach
country: United States
facility: Treasure Coast Infectious Disease Consultant (TDIDC)
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium Atlanta (ARCA)
state: Georgia
city: Chicago
country: United States
facility: Northern Healthcare
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Department of Medicine
state: Indiana
city: Baltimore
country: United States
facility: Institute of Human Virology
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Community Research Initiative of New England
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Tufts University School of Medicine
state: Massachusetts
city: Springfield
country: United States
facility: Community Research Initiative of New England (CRI West)
state: Massachusetts
city: Minneapolis
country: United States
facility: Hennepin County Medical Centre
state: Minnesota
city: New York
country: United States
facility: AIDS Community Research Initiative of America
state: New York
city: New York
country: United States
facility: Bellevue Hospital Center New York University
state: New York
city: New York
country: United States
facility: St Luke's Roosevelt Hospital Centre
state: New York
city: New York
country: United States
facility: St Vincent Catholic Medical Centre
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Portland
country: United States
facility: Fanno Creek Clinic, LLC
state: Oregon
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Dallas
country: United States
facility: Dallas VA Medical Centre
state: Texas
city: Houston
country: United States
facility: The University of Texas Medical School
state: Texas
city: Annandale
country: United States
facility: Infectious Disease Physicians Inc.
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Calgary
country: Canada
facility: Southern Alberta Clinic
state: Alberta
city: Vancouver
country: Canada
facility: St-Paul's Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Sunnybrook and Women College Health Sciences Centre
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Hospital
state: Ontario
city: Montreal
country: Canada
facility: Clinique Médicale du Quartier Latin
state: Quebec
city: Montreal
country: Canada
facility: Clinique Médicale L'Actuel
state: Quebec
city: Montreal
country: Canada
facility: Montreal General Hospital
state: Quebec
Study officials:
affiliation: Massachusetts General Hospital
name: Steven Grinspoon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fourman LT, Czerwonka N, Feldpausch MN, Weiss J, Mamputu JC, Falutz J, Morin J, Marsolais C, Stanley TL, Grinspoon SK. Visceral fat reduction with tesamorelin is associated with improved liver enzymes in HIV. AIDS. 2017 Oct 23;31(16):2253-2259. doi: 10.1097/QAD.0000000000001614.
citation: Stanley TL, Falutz J, Marsolais C, Morin J, Soulban G, Mamputu JC, Assaad H, Turner R, Grinspoon SK. Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin. Clin Infect Dis. 2012 Jun;54(11):1642-51. doi: 10.1093/cid/cis251. Epub 2012 Apr 10.
citation: Falutz J, Mamputu JC, Potvin D, Moyle G, Soulban G, Loughrey H, Marsolais C, Turner R, Grinspoon S. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab. 2010 Sep;95(9):4291-304. doi: 10.1210/jc.2010-0490. Epub 2010 Jun 16.
citation: Falutz J, Allas S, Blot K, Potvin D, Kotler D, Somero M, Berger D, Brown S, Richmond G, Fessel J, Turner R, Grinspoon S. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007 Dec 6;357(23):2359-70. doi: 10.1056/NEJMoa072375.
citation: Falutz J, Potvin D, Mamputu JC, Assaad H, Zoltowska M, Michaud SE, Berger D, Somero M, Moyle G, Brown S, Martorell C, Turner R, Grinspoon S. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension. J Acquir Immune Defic Syndr. 2010 Mar;53(3):311-22. doi: 10.1097/QAI.0b013e3181cbdaff.