Trial record 11 of 14 for:    nichd Cushing's Syndrome

Prospective, Open-Label, Multicenter, International Study of Mifepristone for Symptomatic Treatment of Cushing's Syndrome Caused by Ectopic Adrenal Corticotrophin Hormone (ACTH) Secretion

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
HRA Pharma
ClinicalTrials.gov Identifier:
NCT00422201
First received: January 12, 2007
Last updated: October 14, 2013
Last verified: August 2013
  Purpose

This study will evaluate whether the drug mifepristone can improve the symptoms of Cushing's syndrome in people with ectopic adrenal corticotrophin hormone (ACTH) secretion. Cushing's syndrome occurs when the adrenal glands produce too much cortisol, a hormone that helps to regulate the body's use of salt and food. Excessive cortisol is usually the result of too much ACTH, the hormone that causes the adrenal glands to make cortisol. The extra ACTH is made either by a tumor in the pituitary gland (called Cushing's disease) or by a tumor somewhere else (called ectopic ACTH secretion). Mifepristone blocks the action of cortisol in the body. The drug has been used safely to treat a few people with Cushing's syndrome and patients with certain kinds of cancer, gynecological diseases and psychiatric disorders.

People between 18 and 85 years of age with Cushing's syndrome caused by EXCESS ACTH secretion may be eligible for this study. Candidates are admitted to the hospital for evaluation to confirm Cushing's syndrome and to determine its cause. The evaluation includes blood and urine tests, imaging tests, dexamethasone and corticotropin-releasing hormone tests and inferior petrosal sinus sampling. Patients determined to have Cushing's syndrome due to ECTOPIC ACTH secretion undergo imaging studies (CT, MRI and a nuclear medicine scan) and begin mifepristone therapy.

Participants remain in the hospital for the following tests and procedures:

  • Physical examination, electrocardiogram (EKG) and blood and urine tests
  • Completion of medical questionnaires
  • DEXA scan to determine bone mineral density and body composition
  • Glucose tolerance test
  • Urine pregnancy test and ultrasound to measure uterine lining thickness (for women)

Patients take mifepristone by mouth 3 times a day. The dose is increased every week or so until symptoms improve or the highest dosage allowed is reached. Patients may remain in the hospital for all or part of the dose-finding part of the study. During this period (usually 2 to 4 weeks), blood pressure, glucose tolerance and blood chemistries are measured and EKG and urinalysis done every 5 to 14 days. When the mifepristone dose is stable patients remain on that dose for at least 2 weeks and are then re-evaluated. Patients then return to the hospital for evaluations every 3 months. Those who do well on the drug may continue to take it for up to 12 months.


Condition Intervention Phase
Cushing's Syndrome
Drug: Mifepristone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective, Open-Label, Multicenter, International Study of Mifepristone for Symptomatic Treatment of Cushing's Syndrome Caused by Ectopic Adrenal Corticotrophin Hormone (ACTH) Secretion

Resource links provided by NLM:


Further study details as provided by HRA Pharma:

Primary Outcome Measures:
  • Glycemic Disorders Improved or Normalized [ Time Frame: 8 weeks at steady dose ] [ Designated as safety issue: No ]

    Criteria for improvement or normalization of glycemic disorders:

    A. For diabetic patients (known or diagnosed at pre-inclusion visit)

    • Decrease in HbA1c > 0.3% B. For patients with IGT
    • Normalization of OGTT (2-hour glucose plasma level after 75 g OGTT < 7.8 mmol/L (140 mg/dL) D. For patients with IFG

    If impaired fasting glucose is also associated with impaired glucose tolerance during OGTT at pre-inclusion:

    - Normalization of OGTT (2-hour glucose plasma level after 75 g OGTT < 7.8 mmol/L (140 mg/dL)

    If impaired fasting glycemia is associated with normal OGTT at pre-inclusion (except at T0):

    - Normalization of fasting plasma glucose (fasting plasma glucose < 5.5 mmol/L (100 mg/dL)



Secondary Outcome Measures:
  • Features of Cushing's Syndrome [ Time Frame: 8 weeks at steady dose ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: December 2006
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Mifepristone
    Singe dose
Detailed Description:

Between 10% and 20% of patients with hypercortisolism (Cushing's Syndrome) have tumoral ectopic production of adrenocorticotropin hormone (ACTH) that causes cortisol excess. If an ectopic tumor cannot be found or if surgery cannot be done, the treatment options include medicines that reduce cortisol production and bilateral adrenalectomy. The available medications that reduce cortisol production have important adverse effects and are not effective in some patients and adrenalectomy leads to lifelong requirements for medical hormone replacement. Thus, additional treatment options would be welcome. This study evaluates a potential new medication for the treatment of these patients; mifepristone blocks the effects of cortisol rather than decreasing its production. The purpose of this study is to see whether this agent can improve diabetes or other symptoms of Cushing's syndrome in subjects with ectopic ACTH secretion. Another purpose is to evaluate adverse effects with this drug. Patients with presumed ectopic ACTH secretion and diabetes will take mifepristone 600 mg daily by mouth, and the effect on diabetes and other symptoms of Cushing's syndrome will be measured. Subjects will return to the hospital at 2, 3, 6, 9, and 12 months after starting mifepristione for evaluation of diabetes and other symptoms. The agent will be available for up to 12 months for patients in whom it is effective.

Patients take mifepristone by mouth 3 times a day. Each dose will contain 200 mg. Patients may remain in the hospital for all or part of the initial safety studies, every two weeks for eight weeks. During this period blood pressure, glucose tolerance and blood chemistries are measured and EKG and urinalysis done every two weeks. The mifepristone dose can be decreased or stopped if there are adverse effects. When the mifepristone dose is stable for eight weeks, patients will be re-evaluated. Patients then return to the hospital for evaluations one month later and then every 3 months. Those who do well on the drug may continue to take it for up to 12 months.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Subjects will be included if they have ALL of the three following criteria:

  1. Hypercortisolism from Cushing's syndrome caused by ACTH ectopic secretion

    AND

  2. Glycemic disorder that is considered to be caused or worsened by the hypercortisolism

    AND

  3. At least one symptom attributable to the Cushing's syndrome.

    EXCLUSION CRITERIA:

    • Evidence for Cushing's disease as judged by positive inferior petrosal sinus sampling or a lesion on pituitary MRI with positive CRH test
    • Suspected or known adrenocortical cancer or adenomas, as judged by ACTH values less than 10 pg/ml and adrenal mass
    • Subjects with cyclic Cushing's syndrome defined by any measurement of Urinary Free Cortisol over the previous 2 months less than 2 N
    • Children (age less than 18) and patients over 85 years
    • Pregnant or lactating women. A urinary pregnancy test will be performed in women of childbearing potential unless they have a history of menopause prior to Cushing's syndrome or hysterectomy
    • Life expectancy less than two months
    • Surgery planned within 8 weeks after inclusion, especially bilateral adrenalectomy
    • Uncontrolled diabetes (plasma glucose greater than 15.0 mmol/L (270 mg/L) and/or HbA1c greater than 10%)
    • Uncontrolled hypertension (blood pressure greater than 180/110 mmHg)
    • Recent (less than two weeks prior to inclusion) initiation of corrective treatments for depression
    • Clinically significantly impaired cardiovascular function (e.g. stage IV cardiac failure)
    • Severe liver disease (liver enzymes greater than or equal to 3 x the institutional upper limit of normal range)
    • Severe renal impairment (serum creatinine greater than or equal to 2.2 mg/dl or creatinine clearance less than 30 ml/min)
    • Severe hypokalemia (plasma K below 3.0 mmol/L)
    • Uncontrolled severe active infection
    • In women, known endometrial cancer, history of endometrial hyperplasia or vaginal bleeding of unknown cause
    • Premenopausal women with hemorrhagic disorders or on anticoagulants
    • Recent (less than two weeks prior to inclusion) initiation of or significant change in dose of anti-tumor therapy
    • Previous treatment with approved or experimental steroidogenesis inhibitors, somatostatin analogues within one week of admission (eight weeks for patients on octreotide LAR or on lanreotide autogel)
    • Plasma mitotane concentration greater than 5 microgram/ml
    • Impaired mental capacity or markedly abnormal psychiatric evaluation that precludes informed consent
    • Body weight over 136 kg, which is the limit for the tables used in the scanning areas
    • Inherited porphyria
    • Positive pregnancy test at inclusion
    • Use of antiretroviral agents, midazolam, cabergoline, erythromycin, or grapefruit juice within two weeks of the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00422201

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
France
CHU de Bordeaux Hopital Haut Leveque
Bordeaux, France
C.H.U Albert Michallon
Grenoble, France
C.H.U. de Bicetre
Kremlin-Bicetre, France
CHRU de Lille
Lille, France
Hopital de la Timone
Marseille, France
AP-HP, Hopital Cochin Pavillon CORNIL
Paris, France
CHU de Toulouse
Toulouse, France
Germany
University of Wuerzburg
Wuerzbug, Germany
Italy
Universita Degli Studi
Napoli, Italy
University of Turin
Orbassano, Italy
University of Padova
Padova, Italy
Netherlands
Internal Medicine Endocrinology
Eindhoven, Netherlands
University Hosiptal of Groningen
Groningen, Netherlands
Erasmus Medical Center
Rotterdam, Netherlands
Sponsors and Collaborators
HRA Pharma
Investigators
Principal Investigator: Lynnette K Nieman, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  More Information

Additional Information:
Publications:
Responsible Party: HRA Pharma
ClinicalTrials.gov Identifier: NCT00422201     History of Changes
Other Study ID Numbers: 070008, 07-CH-0008
Study First Received: January 12, 2007
Results First Received: August 8, 2013
Last Updated: October 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by HRA Pharma:
Cortisol
Cushing's Syndrome
Ectopic ACTH Secretion
Cushing Syndrome

Additional relevant MeSH terms:
Cushing Syndrome
Cardiac Complexes, Premature
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Adrenocorticotropic Hormone
Mifepristone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses
Contraceptives, Postcoital, Synthetic
Contraceptives, Postcoital
Hormone Antagonists
Luteolytic Agents
Menstruation-Inducing Agents
Abortifacient Agents, Steroidal
Abortifacient Agents

ClinicalTrials.gov processed this record on April 23, 2014