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New Imaging Techniques in the Evaluation of Patients With Ectopic Cushing Syndrome

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ClinicalTrials.gov Identifier: NCT00001849
Recruitment Status : Completed
First Posted : November 4, 1999
Last Update Posted : May 9, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )

Tracking Information
First Submitted Date  ICMJE November 3, 1999
First Posted Date  ICMJE November 4, 1999
Last Update Posted Date May 9, 2019
Study Start Date  ICMJE February 26, 1999
Actual Primary Completion Date April 26, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2019)
Sensitivity, specificity and diagnostic accuracy of imaging modalities for the detection of ACTH-secreting non-pituitary tumor [ Time Frame: every 6 - 24 months ]
identification of a tumor
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00001849 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE New Imaging Techniques in the Evaluation of Patients With Ectopic Cushing Syndrome
Official Title  ICMJE New Imaging Modalities in the Evaluation of Patients With Ectopic Cushing's Syndrome
Brief Summary

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 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 CT scans, MRIs, 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 [18-F]-fluorodeoxyglucose (FDG) or use of a higher dose of [111In-DTPA-D-Phe]-pentetreotide can be used to successfully localize the source of ectopic ACTH production.<TAB>

Detailed Description Between 10 percent and 20 percent of patients with hypercortisolism (Cushing syndrome) have ectopic production of adrenocorticotropin hormone (ACTH) that causes cortisol excess. In approximately 50 percent of these patients, the source of ACTH cannot be found despite very detailed and extensive examination including imaging studies such as computed tomography scanning, magnetic resonance imaging, and octreotide scan using the conventional low dose of indium-111 pentetreotide ([(111)In-DTPA-D-Phe]-pentetreotide). The sensitivity and specificity of these imaging studies depends on anatomic alterations and/or the dose and adequate uptake of radiopharmaceutical. In contrast, positron emission tomography (PET) has the ability to detect pathologic tissue based on physiologic and biochemical processes within the abnormal tissue. This protocol tests whether [18F]-L-3,4-dihydroxyphenylalanine (18F-DOPA) or use of a higher dose of [111In-DTPA-D-Phe]-pentetreotide can be used to localize successfully the source of ectopic ACTH production. In addition the study examines whether administration of the glucocorticoid antagonist mifepristone can improved the sensitivity of the standard dose Octreocan. Eligible patients participating in this arm of the study will have a second standard dose scan. Others will receive a higher dose octreoscan instead.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE
  • Cushing Syndrome
  • Endocrine Disease
Intervention  ICMJE
  • Drug: Pentetreotide
    Binds primarily to the somatostatin receptors subtypes (sst) 2 and 5
  • Drug: 18F-DOPA
    F-DOPA is a radiolabeled amino acid used as a radiotracer in positron emission tomography.
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 27, 2019)
98
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
202
Actual Study Completion Date  ICMJE April 26, 2019
Actual Primary Completion Date April 26, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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 NIH 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 H-OCT instead, if the L-OCT were negative. Patients with hypokalemia (K < 3.5 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 (PT and PTT elevated by 30 percent above the normal values), hematopoietic (hematocrit less than 30 percent, hemoglobin below 10 g/dl, white count below 3000 K/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 [111In-DTPA-D-Phe]-pentetreotide or other somatostatin analogues.
  • strong evidence for Cushing disease. This includes those with positive IPSS or a lesion on pituitary MRI.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00001849
Other Study ID Numbers  ICMJE 990055
99-CH-0055
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
Study Sponsor  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lynnette K Nieman, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date April 26, 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP