An Oral GnRH Antagonist to Treat Mild Autonomous Cortisol Excess (MACE) Due to Adrenal Adenomas in Postmenopausal Women

Study Overview
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Brief Summary
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The purpose of this research study is to determine if treatment with Elagolix will improve body weight, waist circumference, muscle strength, cortisol secretion, blood glucose, cholesterol, and bone quality as well as mood and quality of life in a female patient with mild hypercortisolism from adrenal overproduction of cortisol. Many people with adrenal nodules, or non-cancerous growths in the adrenal glands, have mildly elevated cortisol levels. Cortisol is a hormone normally made by the adrenal glands. It is increasingly being recognized that even mild elevations in cortisol levels can negatively impact blood glucose levels, serum cholesterol levels, weight and other metabolic parameters. This can lead to an increase in risk for cardiovascular disease. The study team is trying to determine if the medication Elagolix might be an effective treatment for post-menopausal females with mild hypercortisolism. Elagolix is a medication used to treat a medical condition called endometriosis by decreasing the body's production of sex hormones. Growth of adrenal adenomas is thought to be driven by such sex hormones. Therefore, by decreasing production of these hormones, the study team hopes to treat hypercortisolism caused by adrenal adenomas.

Official Title
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An Oral GnRH Antagonist to Treat Mild Autonomous Cortisol Excess (MACE) Due to Adrenal Adenomas in Postmenopausal Women

Conditions
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Mild Autonomous Cortisol Excess

Intervention / Treatment
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* Drug: Elagolix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Post-menopausal women that have incidentally found adrenal adenomas with benign appearing characteristics on imaging (<4 cm, non-contrast CT <10 HU and/or lipid rich and benign appearing on MRI) Absence of anti-anabolic clinical features of overt Cushing's signs (proximal muscle weakness, >three ecchymoses, hyperpigmented striae) and 2 of 3 of the following: Elevated 24 hr urine free cortisol (UFC) above the upper limit of normal (>50 mcg/24 hours) in at least two complete 24-hour tests and/or Late night salivary cortisol more than upper limit of normal in at least two tests and/or an abnormal dexamethasone suppression defined as post 1mg dexamethasone suppression test serum cortisol concentration of >1.8 mcg/ml Clinic status of cessation of menses for 12 mo in a previously cycling woman and reflecting complete or nearly complete permanent cessation of ovarian function and fertility (26). Patients with osteoporosis that are not receiving treatment with either antiresorptive medications (bisphosphonates, denosumab) or anabolic agents (teriparitide, abaloparatide or romosozumab) Exclusion Criteria:
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GnRH antagonist (Elagolix)<br>Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression | Drug: Elagolix<br>* Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cortisol level | Cortisol level after dexamethasone suppression test which measures whether adrenocorticotrophic hormone (ACTH) secretion by the pituitary can be suppressed. | baseline and 6 months | 
| 24 hour urine free cortisol level | 24 hour urine free cortisol measurements. The cortisol urine test measures the level of cortisol in the urine. Cortisol is a glucocorticoid (steroid) hormone produced by the adrenal gland. | Baseline | 
| 24 hour urine free cortisol level | 24 hour urine free cortisol measurements. The cortisol urine test measures the level of cortisol in the urine. Cortisol is a glucocorticoid (steroid) hormone produced by the adrenal gland. | 6 months | 
| Change in adenoma size | All patients will have baseline imaging (CT or MRI) within 6 months to start of treatment and then will have repeat imaging with CT abdomen without contrast at 6 months to determine the effect of elagolix treatment on adrenal adenoma size and imaging characteristics. The images will be reviewed by a dedicated adrenal radiologist for consistency. | Baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight | body weight is measured in kilograms | baseline | 
| Body weight | body weight is measured in kilograms | 3 months | 
| Body weight | body weight is measured in kilograms | 6 months | 
| waist circumference | waist circumference is measured in inches | baseline | 
| waist circumference | waist circumference is measured in inches | 3 months | 
| waist circumference | waist circumference is measured in inches | 6 months | 
| preserved glucose | fasting blood sugar | baseline | 
| preserved glucose | fasting blood sugar | 3 months | 
| preserved glucose | fasting blood sugar | 6 months | 
| Vertebral fractures rates | Vertebral fractures rates will be assessed by lateral X-rays of thoracic and lumbar spine. | baseline | 
| Vertebral fractures rates | Vertebral fractures rates will be assessed by lateral X-rays of thoracic and lumbar spine. | 6 months | 
| The Cushing's Quality of Life Questionnaire | The Cushing's Quality of Life Questionnaire is converted to a 0-100 scale in which 0 indicates the worse and 100 the best possible quality of life. | baseline and 6 months | 
| Beck's Depression Scale | Beck's Depression Scale is scored on a scale of 1 or 40+ where the higher score indicates severe or extreme depression. | baseline and 6 months | 
| State Trait Anxiety Inventory (STAI) | The State Trait Anxiety Inventory gives a score range from 6-24 with the higher score indicating a higher level of anxiety. | baseline and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mild autonomous cortisol excess (MACE), adrenal adenomas, postmenopausal women, GnRH antagonist