A Phase 2 interventional study of Pentetreotide and 18F-DOPA in Cushing Syndrome and Endocrine Disease, sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Completed at 1 site in United States. Open to participants aged 18 Years to 90 Years. Per ClinicalTrials.gov, last updated 2021-04-14.
Sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) · Phase 2, Interventional, and Diagnostic
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.
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 (octreoscan) using the conventional low dose of indium-111 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 fluorine-18 dihydroxyphenylalanine (F-DOPA) or use of a higher dose of indium-111 pentetreotide (Octreoscan) 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 Octreoscan. Eligible patients participating in this arm of the study will have a second standard dose scan. Others will receive a higher dose octreoscan instead.
79 studies on the registry are indexed under Cardiac Complexes, Premature; 13 are open to participants now.
This study's enrollment of 95 is above the median of 86 across 40 interventional studies indexed under Cardiac Complexes, Premature.
Browse Cardiac Complexes, Premature studies →Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is the lead sponsor of 416 studies on the registry; 25 are open to participants now.
Of its 13 completed or terminated interventional studies of FDA-regulated products, 10 (77%) have results posted.
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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:
Patients receive various types of radiologic or nuclear medicine scans to identify tumor
Drug: Pentetreotide · Drug: 18F-DOPA · Device: CT scan · Device: MRI · Drug: 18-FDG
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.
Also known as: [111In-diethylenetriaminepentaacetic acid-D-Phe]-pentetreotide
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.
Also known as: 6-fluoro-L-DOPA, 56494
CT scan of chest, abdomen, neck and /or pelvis
Also known as: computed tomography scan
MRI scan of head/pituitary, chest, abdomen, neck and /or pelvis
Also known as: magnetic resonance imaging scan
FDG PET scan of body
Also known as: 18-fluorine fluorodeoxyglucose PET scan
Sensitivity of Imaging Modalities for the Detection of ACTH-secreting Non-pituitary Tumor in Patients
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.
Time frame: six months or less
Sensitivity of Imaging Modalities for the Detection of ACTH-secreting Non-pituitary Tumor in Specific Lesions
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.
Time frame: six months or less
Patients were recruited based on physician referral to the NIH Clinical Center from 4/1999 to 12/2015. The first participant enrolled on 5/20/99 and the last participant enrolled on 11/19/15. Of 95 enrolled participants, 68 met inclusion criteria and underwent imaging studies.
| Milestone | Patients With Presumed Ectopic ACTH Secretion |
|---|---|
| Started | 68 |
| Completed | 54 |
| Not completed | 14 |
| Withdrew: Death | 4 |
| Withdrew: Lost to follow-up | 2 |
| Withdrew: Withdrawal by subject | 2 |
| Withdrew: Tumor remained occult | 6 |
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.
| percentage of patients | CT Scan Results | Magnetic Resonance Imaging (MRI) Results | Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Results | [18F]-L-3,4-dihydroxyphenylalanine (18F-DOPA) PET Results | Standard Dose Pentetreotide Results | High Dose (18 mCi) Pentetreotide Results |
|---|---|---|---|---|---|---|
| Sensitivity of Imaging Modalities for the Detection of ACTH-secreting Non-pituitary Tumor in Patients | 96.3 (87.7 to 99.0) | 77.1 (61.2 to 85.1) | 66.7 (35.4 to 87.9) | 100 (85.7 to 100) | 45.1 (32.3 to 58.6) | 42.9 (24.5 to 63.5) |
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.
| percentage of lesions | CT Scan Results | MRI Results | FDG-PET Results | F-DOPA PET Results | Standard Dose Pentetreotide Results | High Dose (18 mCi) Octreotide Results |
|---|---|---|---|---|---|---|
| Sensitivity of Imaging Modalities for the Detection of ACTH-secreting Non-pituitary Tumor in Specific Lesions | 75.4 (64 to 84) | 67.3 (53.4 to 77.8) | 46.2 (23.2 to 71) | 95.8 (79.8 to 99.3) | 40.4 (28.6 to 53.3) | 40.9 (23.3 to 61.3) |
Collected over Adverse events (AEs) were monitored during each inpatient admission, generally 7 - 14 days.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Patients With Cushing Syndrome | 4/68 (5.9%) | 0/65 (0%) | 0/65 (0%) |
| Age, Continuous(years) | Patients With Presumed Ectopic ACTH Secretion |
|---|---|
| Mean | 48.1 ± 13.2 |
| Sex: Female, Male(Participants) | Patients With Presumed Ectopic ACTH Secretion |
|---|---|
| Female | 34 |
| Male | 34 |
| Ethnicity (NIH/OMB)(Participants) | Patients With Presumed Ectopic ACTH Secretion |
|---|---|
| Hispanic or Latino | 3 |
| Not Hispanic or Latino | 65 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Patients With Presumed Ectopic ACTH Secretion |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 3 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 9 |
| White | 53 |
| More than one race | 0 |
| Unknown or Not Reported | 3 |
| Region of Enrollment(participants) | Patients With Presumed Ectopic ACTH Secretion |
|---|---|
| United States | 68 |
| Participants with presumed ectopic corticotropin (ACTH) syndrome(Participants) | Patients With Presumed Ectopic ACTH Secretion |
|---|---|
| Count of participants | 68 |
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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)