Mild Autonomous Cortisol Excess
Conditions
Keywords
mild autonomous cortisol excess (MACE), adrenal adenomas, postmenopausal women, GnRH antagonist
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.
Interventions
DRUGElagolix
Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
Sponsors
AbbVie
Icahn School of Medicine at Mount Sinai
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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. |
| 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. |
| Preserved Glucose | baseline and 6 months | fasting blood sugar |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GnRH Antagonist (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
Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | GnRH Antagonist (Elagolix) | — |
|---|---|---|
| Age, Continuous | 64.25 years STANDARD_DEVIATION 5.37 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 4 Participants | — |
| Sex: Female, Male Male | 0 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
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).
Time frame: Baseline and 6 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| GnRH Antagonist (Elagolix) | 24 Hour Urine Free Cortisol Level | baseline | 14 ug/24 hour |
| GnRH Antagonist (Elagolix) | 24 Hour Urine Free Cortisol Level | 6 months | 23 ug/24 hour |
Primary
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.
Time frame: Baseline and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GnRH Antagonist (Elagolix) | Change in Adenoma Size as Compared to Baseline | baseline (MRI) Right | 1.78 cm | Standard Deviation 0.26 |
| GnRH Antagonist (Elagolix) | Change in Adenoma Size as Compared to Baseline | 6 months (CT) Right | 1.8 cm | Standard Deviation 0.22 |
| GnRH Antagonist (Elagolix) | Change in Adenoma Size as Compared to Baseline | baseline (MRI) Left | 2.33 cm | Standard Deviation 1.27 |
| GnRH Antagonist (Elagolix) | Change in Adenoma Size as Compared to Baseline | 6 months (CT) Left | 2.13 cm | Standard Deviation 1.29 |
Primary
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)
Time frame: baseline and 6 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| GnRH Antagonist (Elagolix) | Change in Cortisol Level | Baseline Salivary #1 | 0.252 ng/mL |
| GnRH Antagonist (Elagolix) | Change in Cortisol Level | Baseline Salivary #2 | 0.092 ng/mL |
| GnRH Antagonist (Elagolix) | Change in Cortisol Level | 6 months Salivary #1 | 0.092 ng/mL |
| GnRH Antagonist (Elagolix) | Change in Cortisol Level | 6 months Salivary #2 | 0.4355 ng/mL |
Primary
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).
Time frame: Baseline and 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GnRH Antagonist (Elagolix) | Number of Participants With Change in 24 Hour Urine Free Cortisol Level | 1 Participants |
Primary
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.
Time frame: Baseline and 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GnRH Antagonist (Elagolix) | Number of Participants With Change in Adenoma Size as Compared to Baseline | 0 Participants |
Primary
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.
Time frame: baseline and 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GnRH Antagonist (Elagolix) | Number of Participants With Change in Cortisol Level | 2 Participants |
Secondary
Beck's Depression Scale
Beck's Depression Scale is scored on a scale of 1 to 40, where the higher score indicates severe or extreme depression.
Time frame: baseline and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GnRH Antagonist (Elagolix) | Beck's Depression Scale | baseline | 29 score on a scale | Standard Deviation 10.1 |
| GnRH Antagonist (Elagolix) | Beck's Depression Scale | 6 months | 22 score on a scale | Standard Deviation 8.3 |
Secondary
Change in Body Weight as Compared to Baseline
Mean percent change in body weight is measured in kilograms at 6 months compared to baseline
Time frame: baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GnRH Antagonist (Elagolix) | Change in Body Weight as Compared to Baseline | 1.86 percent change in body weight | Standard Deviation 11.4 |
Secondary
Change in Body Weight for Those Participants Who Lost Weight
Mean percent change in body weight is measured in kilograms at 6 months compared to baseline
Time frame: baseline and 6 months
Population: Data for participants who lost weight
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GnRH Antagonist (Elagolix) | Change in Body Weight for Those Participants Who Lost Weight | -3.86 percent change in body weight | Standard Deviation 0.6 |
Secondary
Number of Participants With Vertebral Fractures
Number of participants with vertebral fractures to measure rates will be assessed by lateral X-rays of thoracic and lumbar spine.
Time frame: baseline and 6 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GnRH Antagonist (Elagolix) | Number of Participants With Vertebral Fractures | Baseline | 0 Participants |
| GnRH Antagonist (Elagolix) | Number of Participants With Vertebral Fractures | 6 months | 0 Participants |
Secondary
Preserved Glucose
fasting blood sugar
Time frame: baseline and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GnRH Antagonist (Elagolix) | Preserved Glucose | Baseline | 136.5 mg/dL | Standard Deviation 51.9 |
| GnRH Antagonist (Elagolix) | Preserved Glucose | 6 months | 126.75 mg/dL | Standard Deviation 41.6 |
Secondary
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.
Time frame: baseline and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GnRH Antagonist (Elagolix) | State Trait Anxiety Inventory (STAI) | baseline | 17 score on a scale | Standard Deviation 5.4 |
| GnRH Antagonist (Elagolix) | State Trait Anxiety Inventory (STAI) | 6 months | 12 score on a scale | Standard Deviation 3.8 |
Secondary
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.
Time frame: baseline and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GnRH Antagonist (Elagolix) | The Cushing's Quality of Life Questionnaire | baseline | 70 score on a scale | Standard Deviation 9.2 |
| GnRH Antagonist (Elagolix) | The Cushing's Quality of Life Questionnaire | 6 months | 83 score on a scale | Standard Deviation 7 |
Secondary
Trunk Fat
Trunk Fat composition assessed by DEXA scans at baseline and at 6 months.
Time frame: baseline and 6 months
Population: Data for participants who completed dexa scan at both timepoints
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GnRH Antagonist (Elagolix) | Trunk Fat | Baseline | 44.7 percent of total fat | Standard Deviation 3.9 |
| GnRH Antagonist (Elagolix) | Trunk Fat | 6 months | 42.6 percent of total fat | Standard Deviation 1.6 |