Glucocorticoid Receptor Blockade With Mifepristone in Patients With Mild Adrenal Hypercortisolism

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01990560

Enrollment

Registered

2013-11-21

Start date

2013-11-30

Completion date

2016-09-30

Last updated

2018-03-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Mild Hypercortisolism

Keywords

mild hypercortisolism, Subclinical Cushing's Syndrome, Preclinical Cushing's Syndrome

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.

Interventions

DRUGMifepristone

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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
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
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
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.
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.
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.
Body Mass Index (BMI)	Baseline and 6 months	Change in metabolic syndrome as assessed by BMI

Countries

United States

Participant flow

Participants by arm

Arm	Count
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	8
Total	8

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Mifepristone
Age, Continuous	65.5 years STANDARD_DEVIATION 10.6
Sex: Female, Male Female	3 Participants
Sex: Female, Male Male	5 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 8
other Total, other adverse events	2 / 8
serious Total, serious adverse events	0 / 8

Outcome results

Primary

A1C Level

Change in hyperglycemia assessed by HbA1c, also known as glycated hemoglobin

Time frame: Baseline, 3 months, and 6 months

Arm	Measure	Group	Value (MEAN)	Dispersion
Mifepristone	A1C Level	6 months	6.125 percentage of red blood cells	Standard Deviation 0.72
Mifepristone	A1C Level	Baseline	6.2 percentage of red blood cells	Standard Deviation 0.58
Mifepristone	A1C Level	3 months	6.1375 percentage of red blood cells	Standard Deviation 0.49

Primary

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.