Clinical trial NCT00082628: Treatment of Abnormal Adipose Tissue Accumulation in Human Immunodeficiency Virus (HIV) Patients
Official title: A Phase III, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of the Safety and Efficacy of Serostim®, r-hGH in the Treatment and Maintenance of Human Immunodeficiency HIV-Associated Adipose Redistribution Syndrome, or HARS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Lipodystrophy
Keywords: Growth hormone
Serostim®
Human Adipose Redistribution Syndrome
Human Immunodeficiency Virus lipodystrophy
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
First posted: 2004-05-17
Enrollment: 326
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to determine if Serostim® 4 mg administered daily for 12 weeks as treatment for the abnormal fat accumulation and distribution associated with HIV-associated Adipose Redistribution Syndrome (HARS) reduces Visceral Adipose Tissue (VAT, measured by CT scan) more effectively than placebo.


Eligibility criteria: Inclusion Criteria:

1. Have written laboratory documentation of an HIV infection by one of the following methods:

   * Detectable viral load measured by polymerase chain reaction (PCR) amplification, branched chain DNA (bDNA) signal amplification or the presence of p24 antigen.
   * Presence of HIV antibodies confirmed by either Western blot or immunofluorescence assay.

   Written laboratory documentation of an HIV infection must be obtained prior to randomization. In the absence of documented historical confirmation, an assay of HIV antibodies will be included in the Screening Laboratory Panel. Results will be confirmed with a Western Blot.
2. Have evidence of excess abdominal adipose deposition when measured by the anthropometric methodology, using the following cut off values:

   * Men: Waist circumference \>88.2 cm AND waist: hip ratio \>= 0.95.
   * Women: Waist circumference \>75.3 cm AND waist: hip ratio \>= 0.9.
3. Are taking antiretroviral medication(s) which is (are) approved or is (are) available under a Treatment IND. The regimen must have remained stable for 30 days prior to study entry. Subjects must also agree not to discontinue or to change their regimen for the duration of the study except as judged medically necessary.
4. Have parameter values less than the following limits (using results from the central laboratory):

   * AST, ALT, and amylase \<= 3 times the upper limit of normal (Screening).
   * Fasting triglycerides \<= 1,000 mg/dL (Screening).
   * Fasting glucose \<110 mg/dL (Screening).
   * Two-hour (120 minute) glucose \<140 mg/dL (Screening).
5. Weight \>= 36 kg (79.3 lb)
6. Be between 18 and 60 years of age (inclusive) unless local law dictates different limits.
7. Sufficiently literate in English to be able to comprehend and complete the Quality of Life Questionnaire.
8. Willing and able to comply with the protocol for the duration of the study.
9. Have voluntarily provided written informed consent (with subject authorization under HIPAA), prior to performing any study-related procedure that is not part of normal medical care, and with the understanding that the subject may withdraw consent at any time without prejudice to future medical care.
10. Female subjects must:

    1. Be post menopausal (\>= 1 year) or surgically sterilized (i.e., have undergone tubal ligation or hysterectomy)

       or
    2. Use a contraceptive method for the duration of the study such as:

       * Hormonal contraceptive
       * Intra uterine device
       * Diaphragm with spermicide, or condom with spermicide.

       And
    3. Must be neither pregnant nor breast feeding.
    4. Confirmation that female subjects of childbearing potential are not pregnant must be established by a negative beta-hCG serum pregnancy test during the 14-day screening period prior to Study Day 1. If the beta-hCG serum pregnancy test is performed more than 7 days prior to Study Day 1, a urine pregnancy test must be performed by the site laboratory on Study Day 1 to confirm a negative test result.

Exclusion Criteria:

1. Have an active AIDS-defining opportunistic complication (OC) as defined by the CDC or have had an untreated or suspected serious systemic infection, or have had a persistent fever \>= 101°F (38.3°C) during the 30 days prior to study entry.
2. Any active or past history of malignancy, except for localized cutaneous Kaposi's sarcoma (fewer than 10 lesions, none of which are larger than 2 cm, and not on active therapy). Such exceptions must be confirmed in writing by the Serono Study Director.
3. Have a CNS mass or active CNS process associated with neurological findings.
4. Have unstable or untreated hypertension, defined as \>= 140/90 mm Hg at the time of the Screening Visit, and/or have initiated or changed antihypertensive therapy in the 30 days prior to Study Day 1.
5. Have an acute critical illness treated in an intensive care unit, e.g., due to complications following open heart or abdominal surgery, multiple accidental trauma, or acute respiratory failure.
6. Have a recent history of sleep apnea or intermittent upper respiratory obstruction.
7. Have any condition, which interferes with informed consent or protocol compliance including, but not limited to, active substance abuse and/or dementia.
8. Are unable to comply with the Concomitant Therapy restrictions including:

   * therapy for obesity including therapy with anorexigenic or fat reducing drugs
   * anti-diabetic or insulin sensitizing medications
   * systemic glucocorticoids
   * systemic chemotherapy, interferon or radiation therapy treatment
   * androgenic agents including, but not limited to testosterone, nandrolone, oxandrolone, oxymetholone, etc. (testosterone replacement therapy for hypogonadism is the exception to this exclusion and will be allowed if started \> 30 days prior to Study Day 1)
   * progestational agents, unless used for oral contraception or post-menopausal hormone replacement therapy
   * appetite stimulants
   * investigational agents, unless approved in advance by the study medical director. Specifically, experimental antiretroviral agents are disallowed, unless available under a treatment IND or expanded access program (30 days).
   * Liposuction or other elective plastic surgery
   * AIDS wasting therapy or prior growth hormone treatment other than study drug (for 12 months prior to the screening visit)
9. Have ever been diagnosed with any of the following conditions:

   * Pancreatitis
   * Carpal tunnel syndrome (unless resolved by surgical release)
   * Diabetes mellitus
   * Angina pectoris
   * Coronary artery disease
   * Any disorder associated with moderate to severe edema (e.g., ascites, nephrotic syndrome, congestive heart failure, lymphedema).
10. Allergy or hypersensitivity to growth hormone.
11. Are participating in any other clinical studies.

In order to participate in this trial a subject must meet all of the inclusion and exclusion criteria specified above. Requests for protocol exceptions/exemptions must come from a participating, fully initiated site at which a prospective patient has consented to undergo screening. Exceptions/exemptions are only allowed by the Trial Director. There is no program in place to allow drug for a single patient IND, or for an expanded access protocol. This statement holds true for both children and adults.

Primary outcomes:
measure: Treatment Period I: Change From Baseline in Absolute Area of Visceral Adipose Tissue (VAT) at Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Treatment Period I: Change From Baseline in Trunk Fat at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Patient Reported Outcome of Body Image Distress at Week 12
timeFrame: Baseline, Week 12
measure: Treatment Period I: Change From Baseline in Non- High-density Lipoprotein (Non-HDL) Cholesterol at Week 12
timeFrame: Baseline, Week 12
measure: Treatment Period II: Failure Rate at Week 36 Based on Visceral Adipose Tissue (VAT) For Subjects Who Received Serostim® 4 mg in Period I
timeFrame: Week 36
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama/Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: CARE CLINIC - UCLA Medical Center
state: California
city: Palm Springs
country: United States
facility: 1401 N. Palm Canyon
state: California
city: Sacramento
country: United States
facility: Trials Unit Div of Infectious and Immunologic Diseases
state: California
city: San Diego
country: United States
facility: UCSD - AntiViral Research Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco - Div. of Endocrinology
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente
state: California
city: San Francisco
country: United States
facility: Northern California Institute for Research and Education, Inc.
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Medical Ctr Research & Education Institute
state: California
city: West Hollywood
country: United States
facility: AIDS Alliance
state: California
city: Denver
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Washington, D.C.
country: United States
facility: 1640 Rhode Island Avenue, N.W.
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Office Of Dr Gary Richmond
state: Florida
city: Miami
country: United States
facility: 3661 South Miami Avenue
state: Florida
city: Miami
country: United States
facility: Care Resources
state: Florida
city: Sarasota
country: United States
facility: Infectious Disease Associates
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Infectious Disease Research Clinic
state: Indiana
city: Boston
country: United States
facility: Tufts University School of Medicine
state: Massachusetts
city: Boston
country: United States
facility: Community Research Initiative of New England
state: Massachusetts
city: Springfield
country: United States
facility: Community Research Initiative Of New England
state: Massachusetts
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell Universtiy
state: New York
city: New York
country: United States
facility: St. Luke's Roosevelt Hospital
state: New York
city: The Bronx
country: United States
facility: Bronx Women's Interagency HIV Study
state: New York
city: Austin
country: United States
facility: Central Texas Clincial research
state: Texas
city: Annandale
country: United States
facility: IDP Research
state: Virginia
city: Spokane
country: United States
facility: Office of Daniel Coulston, M.D.
state: Washington
city: Vancouver
country: Canada
facility: AIDS Research Program
state: British Columbia
Study officials:
affiliation: EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: