Glucocorticoid Receptor Blockade With Mifepristone in Patients With Mild Adrenal Hypercortisolism

Study Overview
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Brief Summary
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The purpose of this study is to determine whether mifepristone is an effective treatment for hyperglycemia due to mild hypercortisolism. To test the hypothesis that GR blockade with mifepristone will decrease the severity of metabolic syndrome features as measured by waist circumference, lipid profile, body mass index, blood pressure and insulin resistance, measured by HOMA-IR score. To test the hypothesis that GR blockade with mifepristone will improve QoL, depression and anxiety scores, measured by validated assessments, in patients with mild hypercortisolism.

Official Title
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Glucocorticoid Receptor Blockade With Mifepristone in Patients With Mild Adrenal Hypercortisolism

Conditions
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Mild Hypercortisolism

Intervention / Treatment
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* Drug: Mifepristone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >18 years of age Incidentally noted adrenal nodule <4 cm with benign imaging characteristics Evidence of mild hypercortisolism Evidence of diabetes or abnormal glucose tolerance Exclusion Criteria: contraindication to mifepristone Indication for unilateral adrenalectomy Evidence of other adrenal hormone hypersecretion lactating mothers women of childbearing age unwilling to use an effective, nonhormonal form of contraception

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Mifepristone<br>Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response | Drug: Mifepristone<br>* All patients in the study will receive daily Mifepristone for 6 months and primary and secondary outcomes will be assessed before and after the 6 month treatment period<br>* Other names: Korlym;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A1C Level | Change in hyperglycemia assessed by HbA1c, also known as glycated hemoglobin | Baseline, 3 months, and 6 months | 
| HOMA-IR | Change in hyperglycemia assessed by Homeostatic Model Assessment of Insulin Resistance, HOMA-IR (a validated assessment of insulin resistance). HOMA-IR = fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5. | Baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Waist Circumference | Change in metabolic syndrome as assessed by waist circumference | Baseline and 6 months | 
| Body Mass Index (BMI) | Change in metabolic syndrome as assessed by BMI | Baseline and 6 months | 
| Fasting Lipid Profile | Change in metabolic syndrome as assessed by fasting lipid profile which includes Low-density lipoproteins ( LDL), High-density lipoproteins (HDL), and Triglycerides (Trigs) levels, and total cholesterol which is the sum of HDL plus LDL and 20% of trigs. | Baseline and 6 months | 
| Weight | Change in metabolic syndrome as assessed by weight | Baseline and 6 months | 
| CushingQoL | Change in Quality of Life - as assessed by the Cushing's Quality of Life questionnaire (CushingQoL). Patient completed questionnaire, 12 items, each scored on a 5 point score, resulting in a score of 12 (worst) to 60 (best) where higher scores indicate more favorable QOL. | Baseline and 6 months | 
| Nottingham Health Profile (NHP) | Change in Quality of Life as assessed by the Nottingham Health Profile (NHP) which is a patient reported questionnaire to measure a patient's view of their own health status. There are 6 sections (Energy level, Pain, Emotional Reaction, Sleep, Social Isolation, and Physical Abilities. All questions have only yes/no answer options and each section score is weighted so that the possible score range for any section is 0-100. The higher the score, the greater the number and severity of problems. | Baseline and 6 months | 
| Hospital Anxiety and Depression Scale (HADS) | Change in Quality of Life as assessed by the Hospital Anxiety and Depression Scale (HADS). Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, with full range from 0 to 42, with higher score indicating more severe anxiety or depression | Baseline and 6 months | 
| Quality of Life | Change in Quality of Life as assessed by the Beck Depression Inventory. a 21-question multiple choice, self-report inventory that is used for measuring the severity of anxiety. Scoring is from a 0 (not at all) to 3 (severe) with a total score range of 0-63. Higher total scores indicate more severe anxiety symptoms. | Baseline and 6 months | 
| State Trait Anxiety Inventory (STAI) | Change in Quality of Life - as assessed by the State Trait Anxiety Inventory (STAI). The State-Trait Anxiety Inventory both state and trait anxiety separately. Each type of anxiety has its own scale of 20 different questions that are scored and averaged. Total scores range from 20 to 80, with higher scores correlating with greater 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 hypercortisolism, Subclinical Cushing's Syndrome, Preclinical Cushing's Syndrome