Glucocorticoid Receptor Blockade With Mifepristone in Patients With Mild Adrenal Hypercortisolism

Phase 4

Completed

Conditions: Mild Hypercortisolism

Interventions: Drug: Mifepristone

Registration Number: NCT01990560

Lead Sponsor: Icahn School of Medicine at Mount Sinai

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 8

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Mifepristone	Mifepristone	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

Primary Outcome Measures

Name	Time	Method
A1C Level	Baseline, 3 months, and 6 months	Change in hyperglycemia assessed by HbA1c, also known as glycated hemoglobin
HOMA-IR	Baseline and 6 months	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.

Secondary Outcome Measures

Name	Time	Method
CushingQoL	Baseline and 6 months	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.
Waist Circumference	Baseline and 6 months	Change in metabolic syndrome as assessed by waist circumference
Fasting Lipid Profile	Baseline and 6 months	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.
Weight	Baseline and 6 months	Change in metabolic syndrome as assessed by weight
Body Mass Index (BMI)	Baseline and 6 months	Change in metabolic syndrome as assessed by BMI
Nottingham Health Profile (NHP)	Baseline and 6 months	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.
Quality of Life	Baseline and 6 months	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.
Hospital Anxiety and Depression Scale (HADS)	Baseline and 6 months	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
State Trait Anxiety Inventory (STAI)	Baseline and 6 months	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.