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

Phase 4

Terminated

Conditions: Mild Autonomous Cortisol Excess

Interventions: Drug: Elagolix

Registration Number: NCT05038878

Lead Sponsor: Icahn School of Medicine at Mount Sinai

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 4

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

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
GnRH antagonist (Elagolix)	Elagolix	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

Primary Outcome Measures

Name	Time	Method
Number of Participants With Change in Cortisol Level	baseline and 6 months	Cortisol level after dexamethasone suppression test which measures whether adrenocorticotrophic hormone (ACTH) secretion by the pituitary can be suppressed. Number of participants with interval improvement and normalization of late-night salivary results after 6 months of treatment.
Change in Cortisol Level	baseline and 6 months	Cortisol level after dexamethasone suppression test which measures whether adrenocorticotrophic hormone (ACTH) secretion by the pituitary can be suppressed. Cortisol secretion as reported below by assessment of pre-treatment and post-treatment of late-night salivary cortisol levels (normal midnight values: \<0.010 - 0.090)
Number of Participants With Change in 24 Hour Urine Free Cortisol Level	Baseline and 6 months	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. Number of participants with improvement in 24-hour urinary free cortisol after treatment (normal 24-hr urinary cortisol is between 6 - 42 ug/24 hr).
24 Hour Urine Free Cortisol Level	Baseline and 6 months	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. Cortisol secretion as reported below by assessment of pre-treatment and post-treatment of 24-hour urinary cortisol levels (normal 24-hr urinary cortisol is between 6 - 42 ug/24 hr).
Number of Participants With Change in Adenoma Size as Compared to Baseline	Baseline and 6 months	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.
Change in Adenoma Size as Compared to Baseline	Baseline and 6 months	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.

Secondary Outcome Measures

Name	Time	Method
Change in Body Weight as Compared to Baseline	baseline and 6 months	Mean percent change in body weight is measured in kilograms at 6 months compared to baseline
Change in Body Weight for Those Participants Who Lost Weight	baseline and 6 months	Mean percent change in body weight is measured in kilograms at 6 months compared to baseline
Trunk Fat	baseline and 6 months	Trunk Fat composition assessed by DEXA scans at baseline and at 6 months.
Number of Participants With Vertebral Fractures	baseline and 6 months	Number of participants with vertebral fractures to measure rates will be assessed by lateral X-rays of thoracic and lumbar spine.
The Cushing's Quality of Life Questionnaire	baseline and 6 months	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.
Beck's Depression Scale	baseline and 6 months	Beck's Depression Scale is scored on a scale of 1 to 40, where the higher score indicates severe or extreme depression.
State Trait Anxiety Inventory (STAI)	baseline and 6 months	The State Trait Anxiety Inventory gives a score range from 6-24 with the higher score indicating a higher level of anxiety.
Preserved Glucose	baseline and 6 months	fasting blood sugar