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

NCT ID: NCT00001079

Last Updated: 2021-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 2002-12-31

Brief Summary

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.

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.

Conditions

HIV Infections; HIV Wasting Syndrome

Keywords

Placebos; Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; HIV Wasting Syndrome; Megestrol Acetate; dihydrotestosterone heptanoate

Study Design

• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT

Interventions

Testosterone enanthate

Intervention Type: DRUG

Megestrol acetate

Intervention Type: DRUG

Eligibility 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Schambelan M

Role: STUDY_CHAIR

Mulligan K

Role: STUDY_CHAIR

Von Roenn JH

Role: STUDY_CHAIR

Locations

USC CRS

Los Angeles, California, United States

UCLA CARE Center CRS

Los Angeles, California, United States

Ucsf Aids Crs

San Francisco, California, United States

University of Colorado Hospital CRS

Aurora, Colorado, United States

Howard University Hosp., Div. of Infectious Diseases, ACTU

Washington D.C., District of Columbia, United States

Queens Med. Ctr.

Honolulu, Hawaii, United States

Univ. of Hawaii at Manoa, Leahi Hosp.

Honolulu, Hawaii, United States

Northwestern University CRS

Chicago, Illinois, United States

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

Indiana Univ. School of Medicine, Wishard Memorial

Indianapolis, Indiana, United States

Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU

New Orleans, Louisiana, United States

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, United States

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, United States

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, United States

Washington U CRS

St Louis, Missouri, United States

Beth Israel Med. Ctr. (Mt. Sinai)

New York, New York, United States

Cornell University A2201

New York, New York, United States

Memorial Sloan-Kettering Cancer Ctr.

New York, New York, United States

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, United States

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, United States

Countries

United States

References

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)

Reference Type: BACKGROUND

Other Identifiers

11288

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 313

Identifier Type: -

Identifier Source: org_study_id