Adrenal Suppression and Adrenal Recovery Induced by Megestrol Acetate

Study Overview
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Brief Summary
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Megestrol Acetate (MA) is a progesterone-like hormone that has been utilized as a birth control agent, chemotherapeutic drug, and more recently, to induce appetite and weight gain in patients malnourished as a result of radiation therapy, chemotherapy, cystic fibrosis, AIDS, or dementia. The mechanism of MA-stimulated appetite and weight gain is unknown. Although only approved to combat weight loss associated with AIDS and cancer, MA is frequently prescribed for long periods of time to prevent or reverse weight loss in nursing home residents and in elderly patients with serious illnesses in the community. Little data is available to support this practice. Among its many properties, MA acts as a partial glucocorticoid agonist, and long term and short term use of MA may results in adrenal suppression. The rapidity of the onset of MA-induced adrenal suppression and the time course of resumption of normal adrenal function after discontinuation of MA is completely unknown. As a consequence, it is unclear whether MA can be given safely for short periods of time or whether glucocorticoid administration is necessary after abruptly stopping MA treatment. The increased use of MA in the frail elderly, where even partial adrenal insufficiency may pose a substantial risk of adrenal crisis after an illness, requires a clear understanding of these issues. To address these concerns, we will evaluate adrenal function before, during, and after MA administration in healthy volunteers between the ages of 60 and 85 years.

Official Title
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Evaluation of the Time Course of Adrenal Suppression and Adrenal Recovery After Ingestion of Megestrol Acetate

Conditions
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Adrenal Insufficiency

Intervention / Treatment
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* Drug: megestrol acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Elderly males and females Age 65-80 years With stable (no history of urgent/ emergent care visits with health care provider/s in the preceding 2 months), medical conditions Exclusion Criteria: Subjects will be excluded if they have a history of (H/O): Dementia Adrenal disease Thromboembolism Diabetes mellitus Liver disease Electrolyte abnormalities; or Vaginal bleeding Hypertriglyceridemia CAD with CHF Unstable depression Schizophrenia; and Morbidly obese subjects.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: megace treatment<br>Study subjects will be given 600mg of MA for oral ingestion per day for duration of 8 weeks. They will be monitored every week clinically for the development of adrenal insufficiency by review of symptoms, physical exam, body weight, pulse, and blood pressure. Subjects also will undergo biochemical evaluation of adrenal status every two weeks by measurement of serum electrolytes, serum cortisol, serum adrenocorticotropic hormone(ACTH) levels, and the adrenal response to a low dose ACTH (1µgm) stimulation test(see methods). | Drug: megestrol acetate<br>* 600 mg by mouth daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adrenal Insufficiency | Number of participants with adrenal insufficiency after treatment with megestrol acetate assessed by ACTH stimulated cortisol levels less than normal (21 ug/dl) measured weekly for 8 weeks or when adrenal insufficiency is clinically encountered | stimulated acth stimulated cortisol levels weekly for 8 weeks or until adrenal insufficiency is encountered | 
| Time Required for Recovery From Adrenal Suppression to Normal Adrenal Function | the number of weeks required for participants to recover from adrenal suppression as assessed by a normal ACTH stimulation test (cortisol level >21 mcg/dl) | weekly for up to 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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megestrol acetate, adrenal insufficiency, adrenal suppression