Mild Hypercortisolism Clinical Trial
Official title:
Glucocorticoid Receptor Blockade With Mifepristone in Patients With Mild Adrenal Hypercortisolism
| Verified date | January 2018 |
| Source | Icahn School of Medicine at Mount Sinai |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 8 |
| Est. completion date | September 2016 |
| Est. primary completion date | September 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | Icahn School of Medicine at Mount Sinai | New York | New York |
| Lead Sponsor | Collaborator |
|---|---|
| Icahn School of Medicine at Mount Sinai |
United States,
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. — View Citation
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. Review. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. Review. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
Tauchmanovà 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. — View Citation
Terzolo M, Pia A, Alì 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. — View Citation
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. Review. — View Citation
* Note: There are 12 references in all — Click here to view all references
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | A1C Level | Change in hyperglycemia assessed by HbA1c, also known as glycated hemoglobin | Baseline, 3 months, and 6 months | |
| 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. | Baseline and 6 months | |
| Secondary | Waist Circumference | Change in metabolic syndrome as assessed by waist circumference | Baseline and 6 months | |
| Secondary | Body Mass Index (BMI) | Change in metabolic syndrome as assessed by BMI | Baseline and 6 months | |
| Secondary | 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 | |
| Secondary | Weight | Change in metabolic syndrome as assessed by weight | Baseline and 6 months | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 | |
| Secondary | 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 |