Glucocorticoid Receptor Blockade With Mifepristone in Patients With Mild Adrenal Hypercortisolism

• ClinicalTrials.gov Identifier: NCT01990560
• Recruitment Status: Completed
• First Posted: November 21, 2013
• Results First Posted: March 2, 2018
• Last Update Posted: March 2, 2018
• Sponsor: Icahn School of Medicine at Mount Sinai
• Information provided by (Responsible Party): Alice C. Levine, Icahn School of Medicine at Mount Sinai

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Mild Hypercortisolism
• Intervention: Drug: Mifepristone
• Enrollment: 8

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Mifepristone
Arm/Group Description	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
Period Title: Overall Study
Started	8
Completed	7
Not Completed	1
Reason Not Completed
Withdrawal by Subject	1

Baseline Characteristics

Arm/Group Title		Mifepristone
Arm/Group Description		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
Overall Number of Baseline Participants		8
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	8 participants
		65.5 (10.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants
	Female	3 37.5%
	Male	5 62.5%

Outcome Measures

1. Primary Outcome

Title	A1C Level
Description	Change in hyperglycemia assessed by HbA1c, also known as glycated hemoglobin
Time Frame	Baseline, 3 months, and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description:	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
Overall Number of Participants Analyzed	8
Mean (Standard Deviation); Unit of Measure: percentage of red blood cells
Baseline	6.2 (0.58)
3 months	6.1375 (0.49)
6 months	6.125 (0.72)

2. Primary Outcome

Title	HOMA-IR
Description	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.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

one participant on insulin. another participant had data missing at 6 months.

Arm/Group Title	Mifepristone
Arm/Group Description:	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
Overall Number of Participants Analyzed	6
Mean (Standard Deviation); Unit of Measure: HOMA-IR score
Baseline	2.418 (1.64)
6 months	1.465 (1.19)

3. Secondary Outcome

Title	Waist Circumference
Description	Change in metabolic syndrome as assessed by waist circumference
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description:	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
Overall Number of Participants Analyzed	8
Mean (Standard Deviation); Unit of Measure: cm
Baseline	103.25 (17.43)
6 months	99.3125 (101.25)

4. Secondary Outcome

Title	Body Mass Index (BMI)
Description	Change in metabolic syndrome as assessed by BMI
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description:	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
Overall Number of Participants Analyzed	8
Mean (Standard Deviation); Unit of Measure: kg/m2
Baseline	35.1538 (15.02)
6 months	34.5463 (15.84)

5. Secondary Outcome

Title	Fasting Lipid Profile
Description	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.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

one participant data missing at 6 month

Arm/Group Title		Mifepristone
Arm/Group Description:		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
Overall Number of Participants Analyzed		8
Mean (Standard Deviation); Unit of Measure: mg/dL
Total Cholesterol Baseline	Number Analyzed	8 participants
		178.63 (31.35)
Total Cholesterol 6 months	Number Analyzed	7 participants
		171.43 (54.62)
LDL baseline	Number Analyzed	8 participants
		97.88 (22.34)
LDL 6 months	Number Analyzed	7 participants
		104.37 (44.69)
HDL Baseline	Number Analyzed	8 participants
		59.13 (19.50)
HDL 6 months	Number Analyzed	7 participants
		46.86 (14.26)
Trigs Baseline	Number Analyzed	8 participants
		107.88 (43.90)
Trigs 6 months	Number Analyzed	7 participants
		100.29 (20.21)

6. Secondary Outcome

Title	Weight
Description	Change in metabolic syndrome as assessed by weight
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

one participant had data missing at 6 months

Arm/Group Title		Mifepristone
Arm/Group Description:		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
Overall Number of Participants Analyzed		8
Mean (Standard Deviation); Unit of Measure: kg
Baseline	Number Analyzed	8 participants
		99.57 (38.68)
6 months	Number Analyzed	7 participants
		97.75 (41.15)

7. Secondary Outcome

Title	CushingQoL
Description	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.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description:	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
Overall Number of Participants Analyzed	7
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	37.2857 (9.86)
6 months	38.7857 (10.20)

8. Secondary Outcome

Title	Nottingham Health Profile (NHP)
Description	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.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description:	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
Overall Number of Participants Analyzed	7
Mean (Inter-Quartile Range); Unit of Measure: units on a scale
Energy Level (EL) Baseline	32.60; (0 to 38)
EL 6 months	45.40; (18 to 72.4)
Pain (P) Baseline	24.88; (0 to 25.1)
P 6 months	32.08; (0 to 44.5)
Emotional Reaction (ER) Baseline	27.03; (0 to 38.7)
ER 6 months	35.09; (7.3 to 54.6)
Sleep (S) Baseline	24.87; (5.4 to 38.8)
S 6 months	31.15; (0 to 46.3)
Social Isolation (SI) Baseline	20.09; (0 to 21)
SI 6 months	31.15; (0 to 46.29)
Physical Abilities (PA) Baseline	23.06; (0 to 48.2)
PA 6 months	27.49; (17.6 to 42.2)

9. Secondary Outcome

Title	Hospital Anxiety and Depression Scale (HADS)
Description	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
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description:	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
Overall Number of Participants Analyzed	7
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	16.2857 (10.90)
6 months	11.1667 (8.23)

10. Secondary Outcome

Title	Quality of Life
Description	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.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description:	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
Overall Number of Participants Analyzed	7
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	16.1429 (10.32)
6 months	11.7143 (11.70)

11. Secondary Outcome

Title	State Trait Anxiety Inventory (STAI)
Description	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.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description:	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
Overall Number of Participants Analyzed	7
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	25.4286 (17.61)
6 months	28.8571 (10.92)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Mifepristone
Arm/Group Description	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
All-Cause Mortality
	Mifepristone
	Affected / at Risk (%)
Total	0/8 (0.00%)
Serious Adverse Events
	Mifepristone
	Affected / at Risk (%)	# Events
Total	0/8 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Mifepristone
	Affected / at Risk (%)	# Events
Total	2/8 (25.00%)
Metabolism and nutrition disorders
Hypokalemia	1/8 (12.50%)	1
Skin and subcutaneous tissue disorders
Drug Rash	1/8 (12.50%)	1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Alice C. Levine
• Organization: Ichan School of Medicine at Mount Sinai
• Phone: 212-241-1500
• EMail: alice.levine@mountsinai.org

Publications:

Young WF Jr. Management approaches to adrenal incidentalomas. A view from Rochester, Minnesota. Endocrinol Metab Clin North Am. 2000 Mar;29(1):159-85, x. doi: 10.1016/s0889-8529(05)70122-5.

Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y, Bornstein SR. The clinically inapparent adrenal mass: update in diagnosis and management. Endocr Rev. 2004 Apr;25(2):309-40. doi: 10.1210/er.2002-0031.

Tauchmanova L, Rossi R, Biondi B, Pulcrano M, Nuzzo V, Palmieri EA, Fazio S, Lombardi G. Patients with subclinical Cushing's syndrome due to adrenal adenoma have increased cardiovascular risk. J Clin Endocrinol Metab. 2002 Nov;87(11):4872-8. doi: 10.1210/jc.2001-011766.

Terzolo M, Pia A, Ali A, Osella G, Reimondo G, Bovio S, Daffara F, Procopio M, Paccotti P, Borretta G, Angeli A. Adrenal incidentaloma: a new cause of the metabolic syndrome? J Clin Endocrinol Metab. 2002 Mar;87(3):998-1003. doi: 10.1210/jcem.87.3.8277.

Garrapa GG, Pantanetti P, Arnaldi G, Mantero F, Faloia E. Body composition and metabolic features in women with adrenal incidentaloma or Cushing's syndrome. J Clin Endocrinol Metab. 2001 Nov;86(11):5301-6. doi: 10.1210/jcem.86.11.8059.

Feelders RA, Hofland LJ. Medical treatment of Cushing's disease. J Clin Endocrinol Metab. 2013 Feb;98(2):425-38. doi: 10.1210/jc.2012-3126. Epub 2013 Jan 23.

Lambert JK, Goldberg L, Fayngold S, Kostadinov J, Post KD, Geer EB. Predictors of mortality and long-term outcomes in treated Cushing's disease: a study of 346 patients. J Clin Endocrinol Metab. 2013 Mar;98(3):1022-30. doi: 10.1210/jc.2012-2893. Epub 2013 Feb 7.

Neary NM, Booker OJ, Abel BS, Matta JR, Muldoon N, Sinaii N, Pettigrew RI, Nieman LK, Gharib AM. Hypercortisolism is associated with increased coronary arterial atherosclerosis: analysis of noninvasive coronary angiography using multidetector computerized tomography. J Clin Endocrinol Metab. 2013 May;98(5):2045-52. doi: 10.1210/jc.2012-3754. Epub 2013 Apr 4.

Debono M, Chadarevian R, Eastell R, Ross RJ, Newell-Price J. Mifepristone reduces insulin resistance in patient volunteers with adrenal incidentalomas that secrete low levels of cortisol: a pilot study. PLoS One. 2013;8(4):e60984. doi: 10.1371/journal.pone.0060984. Epub 2013 Apr 5.

Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM. The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008 May;93(5):1526-40. doi: 10.1210/jc.2008-0125. Epub 2008 Mar 11.

Flint A, Raben A, Blundell JE, Astrup A. Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes Relat Metab Disord. 2000 Jan;24(1):38-48. doi: 10.1038/sj.ijo.0801083.

Parker BA, Sturm K, MacIntosh CG, Feinle C, Horowitz M, Chapman IM. Relation between food intake and visual analogue scale ratings of appetite and other sensations in healthy older and young subjects. Eur J Clin Nutr. 2004 Feb;58(2):212-8. doi: 10.1038/sj.ejcn.1601768.

• Responsible Party: Alice C. Levine, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT01990560
• Other Study ID Numbers: GCO 13-1061
• First Submitted: November 15, 2013
• First Posted: November 21, 2013
• Results First Submitted: October 18, 2017
• Results First Posted: March 2, 2018
• Last Update Posted: March 2, 2018