- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00001849
New Imaging Techniques in the Evaluation of Patients With Ectopic Cushing Syndrome
New Imaging Modalities in the Evaluation of Patients With Ectopic Cushing's Syndrome
Cushing Syndrome is an endocrine disorder causing an over production of the hormone cortisol. Cortisol is produced in the adrenal gland as a response to the production of corticotropin (ACTH) in the pituitary gland.
Between 10% and 20% of patients with hypercortisolism (Cushing Syndrome) have ectopic production of the hormone ACTH. Meaning, the hormone is not being released from the normal site, the pituitary gland. In many cases the ectopic ACTH is being produced by a tumor of the lung, thymus, or pancreas. However, in approximately 50% of these patients the source of the ACTH cannot be found even with the use of extensive imaging studies such as computed tomography (CT) scans, magnetic resonance imaging (MRI), and nuclear scans (111-indium pentetreotide). The ability of these tests to locate the source of the hormone production is dependent on the changes of anatomy and / or the dose and adequate uptake of the radioactive agent. The inability to detect the source of ectopic ACTH production often results in unnecessary pituitary surgery or irradiation.
Unlike the previously described tests, positron emission tomography (PET scan) has the ability to detect pathologic tissue based on physiologic and biochemical processes within the abnormal tissue.
This study will test whether fluorine-18-fluorodeoxyglucose (FDG), fluorine-18-dihydroxyphenylalanine (F-DOPA) or use of a higher dose of 111-indium pentetreotide can be used to successfully localize the source of ectopic ACTH production.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Maryland
-
Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center, 9000 Rockville Pike
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
- INCLUSION CRITERIA:
All eligible patients are invited to participate in this protocol. Patients are adults with possible ectopic Cushing syndrome. Since both men and women are affected with ectopic Cushing syndrome, both sexes are studied. All ethnic and racial groups are at risk and will be included. Patients must be willing to return to the National Institutes of Health (NIH) Clinical Center for follow-up studies.
EXCLUSION CRITERIA:
Pregnant or lactating women. A pregnancy test is performed in women of childbearing potential (up to age 55) unless they have a history of hysterectomy.
Children (age less than18) are excluded. Because ectopic ACTH secretion is rare in this age group, the likelihood of benefit is less and does not balance the risk of radiation.
Patients taking medications that alter CYP3A4 activity will not be eligible for the mifepristone study, since this P450 system metabolizes mifepristone. Such participants would receive a clinical high dose (18 mCi) octreoscan (H-OCT) instead, if the standard 6 mCi octreoscan (L-OCT) was negative. Patients with hypokalemia (K < 3.5 milliequivalent (mEq)/L) despite medical therapy with replacement or mineralocorticoid antagonists will also be excluded from the mifepristone studies.
The presence of:
- severe active infection.
- clinically significantly impaired cardiovascular (e.g., history of abnormally low ejection fraction, the presence of moderate pulmonary fluid overload or leg edema, and blood pressure over 190/100), abnormal coagulation (partial thromboplastin time or prothrombin time elevated by 30 percent above the normal values), hematopoietic (hematocrit less than 30 percent, hemoglobin below 10 g/dl, white count below 3000 K/microliter (UL), and platelets below 100,000 K/mm(3)), hepatic (liver enzymes elevated by 3-fold above normal values) or renal function (plasma creatinine level over 2.0).
- 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.
- combined blood withdrawal, during the six weeks preceding the study, of greater than 450 ml.
- known allergy to 111-indium pentetreotide or other somatostatin analogues.
- strong evidence for Cushing disease. This includes those with positive inferior petrosal sinus sampling or a lesion on pituitary MRI.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Patients with Cushing Syndrome
Patients receive various types of radiologic or nuclear medicine scans to identify tumor
|
Binds primarily to the somatostatin receptors subtypes (sst) 2 and 5.
A high dose (18mCi) was used if the conventional dose (6mCi) was negative and scheduling was available.
High doses limited to 3 over the course of the study.
Other Names:
18F-DOPA is a radiolabeled amino acid used as a radiotracer in positron emission tomography (PET).
Limited to 3 doses over the course of the study.
Other Names:
CT scan of chest, abdomen, neck and /or pelvis
Other Names:
MRI scan of head/pituitary, chest, abdomen, neck and /or pelvis
Other Names:
FDG PET scan of body
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sensitivity of Imaging Modalities for the Detection of ACTH-secreting Non-pituitary Tumor in Patients
Time Frame: six months or less
|
The percentage of patients in whom imaging correctly identified an ACTH-secreting non-pituitary tumor within six months of resection or in which imaging identified a recurrence at a site of previous resection.
|
six months or less
|
Sensitivity of Imaging Modalities for the Detection of ACTH-secreting Non-pituitary Tumor in Specific Lesions
Time Frame: six months or less
|
The percentage of lesions for which imaging correctly identified an ACTH-secreting non-pituitary tumor within six months of resection or for which imaging identified a recurrence at a site of previous resection.
|
six months or less
|
Collaborators and Investigators
Publications and helpful links
General Publications
- Findling JW, Tyrrell JB. Occult ectopic secretion of corticotropin. Arch Intern Med. 1986 May;146(5):929-33.
- Jex RK, van Heerden JA, Carpenter PC, Grant CS. Ectopic ACTH syndrome. Diagnostic and therapeutic aspects. Am J Surg. 1985 Feb;149(2):276-82. doi: 10.1016/s0002-9610(85)80085-4.
- Trainer PJ, Grossman A. The diagnosis and differential diagnosis of Cushing's syndrome. Clin Endocrinol (Oxf). 1991 Apr;34(4):317-30. doi: 10.1111/j.1365-2265.1991.tb03773.x. No abstract available.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Heart Diseases
- Cardiovascular Diseases
- Disease
- Arrhythmias, Cardiac
- Cardiac Conduction System Disease
- Adrenocortical Hyperfunction
- Adrenal Gland Diseases
- Syndrome
- Endocrine System Diseases
- Cushing Syndrome
- Cardiac Complexes, Premature
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Protective Agents
- Anticoagulants
- Antidotes
- Chelating Agents
- Sequestering Agents
- Iron Chelating Agents
- Calcium Chelating Agents
- Edetic Acid
- Pentetic Acid
Other Study ID Numbers
- 990055
- 99-CH-0055 (Other Identifier: National Institutes of Health (NIH) Clinical Center)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cushing Syndrome
-
Centre hospitalier de l'Université de Montréal...Recordati Rare DiseasesActive, not recruitingEndogenous Cushing SyndromeCanada
-
Sparrow PharmaceuticalsRecruitingAutonomous Cortisol Secretion (ACS) | ACTH-Independent Cushing Syndrome | ACTH-Independent Adrenal Cushing Syndrome, SomaticUnited States, United Kingdom, France, Romania
-
University of LeedsCompletedAdrenal; Insufficiency Gluccorticoid-Induced | Cushing; Syndrome or Disease, Glucocorticoid-Induced
-
National Cancer Institute (NCI)Not yet recruitingHyperaldosteronism | Hypercortisolism | Cushing s SyndromeUnited States
-
Assistance Publique - Hôpitaux de ParisCompletedCushing Syndrome Related to Cortisolic AdenomaFrance
-
HRA PharmaRecruitingCushing SyndromeSweden, France, Croatia, Spain
-
RECORDATI GROUPActive, not recruitingCushing's SyndromeUnited States, Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, China, Costa Rica, France, Germany, India, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Thailand, Turkey
-
Eunice Kennedy Shriver National Institute of Child...Completed
-
Corcept TherapeuticsCompletedCushing's SyndromeUnited States
-
HRA PharmaCompletedCushing's SyndromeGermany, Belgium, Italy, Hungary, Poland, Romania, Spain, Turkey
Clinical Trials on Pentetreotide
-
Radio Isotope Therapy of AmericaRadiomedix, Inc.; Excel Diagnostic Imaging Clinics; CHI St. Luke's Health, TexasCompletedNeuroendocrine TumorsUnited States
-
MallinckrodtTerminated
-
Yale UniversityNational Cancer Institute (NCI)TerminatedKidney Cancer | Head and Neck Cancer | Lung Cancer | Brain and Central Nervous System Tumors | Intraocular Melanoma | Melanoma (Skin) | Pheochromocytoma | Islet Cell Tumor | Gastrointestinal Carcinoid Tumor | Neoplastic Syndrome | Neuroendocrine Carcinoma of the Skin | Childhood Langerhans Cell HistiocytosisUnited States
-
Sue O'DorisioNational Cancer Institute (NCI)CompletedNeuroendocrine Tumor | Neuroblastoma | Somatostatinoma | Adult Medulloblastoma | Childhood MedulloblastomaUnited States
-
David BushnellVA Office of Research and DevelopmentCompleted