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

NCT05038878 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: GCO 19-1595
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Mild Autonomous Cortisol Excess

Keywords

mild autonomous cortisol excess (MACE); adrenal adenomas; postmenopausal women; GnRH antagonist

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Change in Cortisol Level

  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.

  baseline and 6 months

• Change in Cortisol Level

  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)

  baseline and 6 months

• Number of Participants With Change in 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. 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).

  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. 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).

  Baseline and 6 months

• Number of Participants With Change in Adenoma Size as Compared to Baseline

  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

• Change in Adenoma Size as Compared to Baseline

  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 Outcomes (8)

• Change in Body Weight as Compared to Baseline

  baseline and 6 months

• Change in Body Weight for Those Participants Who Lost Weight

  baseline and 6 months

• Trunk Fat

  baseline and 6 months

• Preserved Glucose

  baseline and 6 months

• Number of Participants With Vertebral Fractures

  baseline and 6 months

Study Arms (1)

GnRH antagonist (Elagolix)

EXPERIMENTAL

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

Interventions

Elagolix DRUG

Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months

GnRH antagonist (Elagolix)

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• AbbVie: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Interventions

elagolix

Results Point of Contact

• Title: Dr. Alice C. Levine
• Organization: Icahn School of Medicine at Mount Sinai

alice.levine@mountsinai.org

(212) 241-3422

Study Officials

• Alice C Levine

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Medicine - Endocrinology, Diabetes and Bone Disease

Study Record Dates

• First Submitted: August 17, 2021
• First Posted: September 9, 2021
• Study Start: July 6, 2021
• Primary Completion: June 24, 2022
• Study Completion: June 24, 2022
• Last Updated: March 18, 2025
• Results First Posted: March 18, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)