A Study of Megestrol Acetate Alone or in Combination With Testosterone Enanthate Drug in the Treatment of HIV-Associated Weight Loss

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001079
First received: November 2, 1999
Last updated: July 26, 2013
Last verified: July 2013
  Purpose

To test the hypothesis that the predominant accrual of fat rather than lean body mass (LBM) that occurs during treatment of HIV-associated wasting with megestrol acetate may be improved by treatment with megestrol acetate and testosterone enanthate in combination.

Body wasting is an increasingly frequent AIDS-defining condition in individuals infected with HIV. Increasing caloric intake fails to consistently restore lean tissue patients with HIV associated weight loss. Megestrol acetate has been shown to stimulate appetite and weight gain in subjects with cancer and in those with HIV associated weight loss. However, the weight gained during treatment with megestrol acetate was predominantly or exclusively fat. An important factor is the preferential increase in body fat seen in both of these studies may have been due to hypogonadism that occurs as a result of treatment with megestrol acetate, a progestational agent. Hypogonadism is associated with an increase in body fat and a decrease in LBM. Concomitant testosterone replacement should substantially increase the amount of LBM accrued during megestrol acetate therapy. This study will determine whether anabolic potential can be realized when caloric intake is increased in the absence of concomitant hypogonadism.


Condition Intervention Phase
HIV Infections
HIV Wasting Syndrome
Drug: Testosterone enanthate
Drug: Megestrol acetate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: Double-Blind Randomized Comparison Phase II Trial of Megestrol Acetate and Testosterone Enanthate in Combination Versus Megestrol Acetate Plus Testosterone Enanthate Placebo in Human Immunodeficiency Virus (HIV)-Associated Wasting.

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 80
Study Completion Date: December 2002
Detailed Description:

Body wasting is an increasingly frequent AIDS-defining condition in individuals infected with HIV. Increasing caloric intake fails to consistently restore lean tissue patients with HIV associated weight loss. Megestrol acetate has been shown to stimulate appetite and weight gain in subjects with cancer and in those with HIV associated weight loss. However, the weight gained during treatment with megestrol acetate was predominantly or exclusively fat. An important factor is the preferential increase in body fat seen in both of these studies may have been due to hypogonadism that occurs as a result of treatment with megestrol acetate, a progestational agent. Hypogonadism is associated with an increase in body fat and a decrease in LBM. Concomitant testosterone replacement should substantially increase the amount of LBM accrued during megestrol acetate therapy. This study will determine whether anabolic potential can be realized when caloric intake is increased in the absence of concomitant hypogonadism.

This is a 24 week study consisting of a 12 week double blind, randomized comparison Phase II trial of megestrol acetate and testosterone enanthate in combination versus megestrol acetate plus testosterone enanthate placebo in HIV associated wasting and a 12 week open label follow up of the combination therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Stable antiretroviral therapy provided the patient has been on it for >=30 days prior to study entry. AS PER AMENDMENT 9/26/97: Optimized antiretroviral therapy as determined by primary care provider with at least 30 days since initiation of such therapy.
  • Standard maintenance and prophylaxis therapy for opportunistic infections is permitted provided patients have been on a stable dosage regimen for 2 weeks prior to screening.
  • G-CSF.
  • Erythropoietin.
  • Any symptomatic therapy (e.g., analgesics, antihistamines, antiemetic, antidiarrheal agents, etc.).
  • Replacement levels of thyroid drugs (same drug and dose as at 30 days pre-entry).
  • Maintenance therapy is permitted for chronic opportunistic infections, but patient must be on a stable regimen for 14 days pre-entry.
  • AS PER AMENDMENT 9/26/97: Oral nutritional supplements, dronabinol, cyproheptadine, or pentoxifylline.

Patients must have:

  • Documented HIV-1 infection.
  • Documented weight loss of > 10% pre-illness weight or Body Mass Index < 18.5 kg/m2. AS PER AMENDMENT 9/26/97: Documented weight loss of >= 5% pre-illness weight or Body Mass Index < 20 kg/m2.
  • Life expectancy of at least 6 months.

NOTE:

  • This protocol meets federal requirements governing prisoner participation in clinical trials.

Prior Medication:

Allowed:

  • Stable (no change in drugs or dosage) antiretroviral therapy or no antiretroviral medications for >= 30 days prior to the study entry.

Exclusion Criteria

Co-existing Condition:

Patients with any of the following symptoms or conditions are excluded:

  • Diabetes mellitus.
  • Diarrhea defined as 4 or more liquid or watery stools per day while using antidiarrheal medication.
  • Tube feeding. AS PER AMENDMENT 9/26/97: Total or partial parenteral nutrition delivered centrally or peripherally.
  • Impaired oral intake due to mucositis of any cause.
  • Grade 2 or greater intractable nausea and vomiting despite medication.
  • Cardiomyopathy or congestive heart failure.
  • Persistent palpable dominant breast mass at study entry that has not been worked up - males and females.

Female patients:

  • Pap smear or cervical biopsy that demonstrates high grade squamous intraepithelial lesions or cervical intraepithelial lesions 2 or worse.

Concurrent Medication:

Excluded:

  • Systemic chemotherapy for B-cell lymphoma or malignancies other than Kaposi's sarcoma. (Patients with Kaposi's sarcoma receiving systemic chemotherapy will not be excluded.)
  • Total or peripheral parenteral nutrition (oral supplements are not excluded).
  • Anticoagulant therapy.
  • Any drug that is designed to affect appetite or weight gain. AS PER AMENDMENT 9/26/97: Initiation of any new therapy designed to promote weight gain.
  • Any change of antiretroviral or any change in the dosage of antiretroviral/s that had not been started 30 days pre-entry. AS PER AMENDMENT 9/26/97: Initiation of antiretroviral therapy within 12 weeks of protocol therapy for patients not previously receiving antiretroviral therapy.
  • Anabolic hormones.
  • Systemic glucocorticoids.
  • Cytokine inhibitors.
  • Oral contraceptives.
  • Cytokines.
  • Ketoconazole.
  • Any other medication that might interfere with the objectives of this study.
  • AS PER AMENDMENT 9/26/97:DHEA.

Patients with the following prior conditions will be excluded:

  • Acute systemic opportunistic infections within 30 days prior to entry.
  • Weight gain >= 3% as documented by self reporting or clinical records during the preceding 4 weeks. AS PER AMENDMENT 9/26/97: Enrollment of such patients should be deferred until weight stabilizes.
  • History of hypersensitivity reaction to megestrol acetate or testosterone enanthate.
  • History of cardiomyopathy or congestive heart failure.

Female patients:

  • History of invasive cervical cancer.
  • AS PER AMENDMENT 9/26/97: History of thromboemboli.

Prior Medication:

Excluded:

  • No testosterone treatment within the previous 8 weeks.

Excluded within 30 days prior to entry:

  • Ketoconazole.
  • Initiation or change in antiretroviral therapy.
  • Interleukins.
  • Interferon, anabolic, hormonal or experimental therapies designed to improve appetite or weight gain (e.g., thalidomide, dronabinol, megestrol acetate, cyproheptadine, anabolic steroids, systemic glucocorticoids, pentoxifylline, or growth hormone).
  • AS PER AMENDMENT 9/26/97: Dehydroepiandrosterone (DHEA).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001079

Locations
United States, California
USC CRS
Los Angeles, California, United States, 90033
UCLA CARE Center CRS
Los Angeles, California, United States, 90035
Ucsf Aids Crs
San Francisco, California, United States, 94110
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80045
United States, District of Columbia
Howard University Hosp., Div. of Infectious Diseases, ACTU
Washington, District of Columbia, United States, 20060
United States, Hawaii
Queens Med. Ctr.
Honolulu, Hawaii, United States, 96813
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States, 96816
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 46202
Indiana Univ. School of Medicine, Wishard Memorial
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States, 02215
United States, Missouri
St. Louis ConnectCare, Infectious Diseases Clinic
St. Louis, Missouri, United States
Washington U CRS
St. Louis, Missouri, United States
United States, New York
Memorial Sloan-Kettering Cancer Ctr.
New York, New York, United States, 10021
Cornell University A2201
New York, New York, United States, 10021
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, United States, 10003
United States, North Carolina
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, United States, 27710
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Investigators
Study Chair: Schambelan M
Study Chair: Mulligan K
Study Chair: Von Roenn JH
  More Information

Additional Information:
Publications:
Schambelan M, Zackin R, Mulligan K, Sattler FR, Chesney M, Stevens M, Edwards L, Egorin MJ, Von Roenn JH. Effect of testosterone (T) on the response to megesterol acetate (MA) in patients with HIV-associated wasting: a randomized, double-blind placebo-controlled trial (ACTG 313). 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 640)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001079     History of Changes
Other Study ID Numbers: ACTG 313, 11288
Study First Received: November 2, 1999
Last Updated: July 26, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Placebos
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
HIV Wasting Syndrome
Megestrol Acetate
dihydrotestosterone heptanoate

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Cachexia
Wasting Syndrome
HIV Wasting Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Emaciation
Weight Loss
Body Weight Changes
Body Weight
Signs and Symptoms
Metabolic Diseases
Nutrition Disorders
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Megestrol
Megestrol Acetate
Androgens
Hormones

ClinicalTrials.gov processed this record on August 21, 2014