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

Primary Purpose

Mild Autonomous Cortisol Excess

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Elagolix
Sponsored by
Icahn School of Medicine at Mount Sinai
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mild Autonomous Cortisol Excess focused on measuring mild autonomous cortisol excess (MACE), adrenal adenomas, postmenopausal women, GnRH antagonist

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)FemaleDoes not accept healthy volunteers

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:

Sites / Locations

  • Icahn School of Medicine at Mount SinaiRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GnRH antagonist (Elagolix)

Arm Description

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

Outcomes

Primary Outcome Measures

Change in Cortisol level
Cortisol level after dexamethasone suppression test which measures whether adrenocorticotrophic hormone (ACTH) secretion by the pituitary can be suppressed.
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.
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.
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.

Secondary Outcome Measures

Body weight
body weight is measured in kilograms
Body weight
body weight is measured in kilograms
Body weight
body weight is measured in kilograms
waist circumference
waist circumference is measured in inches
waist circumference
waist circumference is measured in inches
waist circumference
waist circumference is measured in inches
preserved glucose
fasting blood sugar
preserved glucose
fasting blood sugar
preserved glucose
fasting blood sugar
Vertebral fractures rates
Vertebral fractures rates will be assessed by lateral X-rays of thoracic and lumbar spine.
Vertebral fractures rates
Vertebral fractures rates will be assessed by lateral X-rays of thoracic and lumbar spine.
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.
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.
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.

Full Information

First Posted
August 17, 2021
Last Updated
July 25, 2023
Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
AbbVie
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1. Study Identification

Unique Protocol Identification Number
NCT05038878
Brief Title
An Oral GnRH Antagonist to Treat Mild Autonomous Cortisol Excess (MACE) Due to Adrenal Adenomas in Postmenopausal Women
Official Title
An Oral GnRH Antagonist to Treat Mild Autonomous Cortisol Excess (MACE) Due to Adrenal Adenomas in Postmenopausal Women
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 6, 2021 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
AbbVie

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Autonomous Cortisol Excess
Keywords
mild autonomous cortisol excess (MACE), adrenal adenomas, postmenopausal women, GnRH antagonist

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
GnRH antagonist (Elagolix)
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Elagolix
Intervention Description
Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
Primary Outcome Measure Information:
Title
Change in Cortisol level
Description
Cortisol level after dexamethasone suppression test which measures whether adrenocorticotrophic hormone (ACTH) secretion by the pituitary can be suppressed.
Time Frame
baseline and 6 months
Title
24 hour urine free cortisol level
Description
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.
Time Frame
Baseline
Title
24 hour urine free cortisol level
Description
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.
Time Frame
6 months
Title
Change in adenoma size
Description
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.
Time Frame
Baseline and 6 months
Secondary Outcome Measure Information:
Title
Body weight
Description
body weight is measured in kilograms
Time Frame
baseline
Title
Body weight
Description
body weight is measured in kilograms
Time Frame
3 months
Title
Body weight
Description
body weight is measured in kilograms
Time Frame
6 months
Title
waist circumference
Description
waist circumference is measured in inches
Time Frame
baseline
Title
waist circumference
Description
waist circumference is measured in inches
Time Frame
3 months
Title
waist circumference
Description
waist circumference is measured in inches
Time Frame
6 months
Title
preserved glucose
Description
fasting blood sugar
Time Frame
baseline
Title
preserved glucose
Description
fasting blood sugar
Time Frame
3 months
Title
preserved glucose
Description
fasting blood sugar
Time Frame
6 months
Title
Vertebral fractures rates
Description
Vertebral fractures rates will be assessed by lateral X-rays of thoracic and lumbar spine.
Time Frame
baseline
Title
Vertebral fractures rates
Description
Vertebral fractures rates will be assessed by lateral X-rays of thoracic and lumbar spine.
Time Frame
6 months
Title
The Cushing's Quality of Life Questionnaire
Description
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.
Time Frame
baseline and 6 months
Title
Beck's Depression Scale
Description
Beck's Depression Scale is scored on a scale of 1 or 40+ where the higher score indicates severe or extreme depression.
Time Frame
baseline and 6 months
Title
State Trait Anxiety Inventory (STAI)
Description
The State Trait Anxiety Inventory gives a score range from 6-24 with the higher score indicating a higher level of anxiety.
Time Frame
baseline and 6 months

10. Eligibility

Sex
Female
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eva L Alba
Phone
212-659-8554
Email
eva.alba@mssm.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Rachel Sheskier, MD
Phone
(646) 251-1573
Email
rachel.sheskier@mssm.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alice C Levine
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eva L Alba
Email
eva.alba@mssm.edu
First Name & Middle Initial & Last Name & Degree
Alice C Levine

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Privacy

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

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