Cushing SyndromePhase 2NCT00001849

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

A Phase 2 study testing Pentetreotide, 18F-DOPA and CT scan in people with Cushing Syndrome and Endocrine Disease, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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 corticotropin (ACTH) in the pituitary gland. Read more about this study

Who is it for?: Ages 18 to 90 years
Conditions the study is for: Cushing Syndrome, Endocrine Disease
What is being tested?: Pentetreotide, 18F-DOPA and CT scan
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 95 participants
Where: 1 siteUnited States
Study dates: 20 May 1999to 26 Apr 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 90 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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).

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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.

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: New Imaging Modalities in the Evaluation of Patients With Ectopic Cushing's Syndrome

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.

Read the 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 (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.

Conditions: Cushing Syndrome, Endocrine Disease
Being tested: Pentetreotide, 18F-DOPA, CT scan, MRI, 18-FDG
Keywords: PET, fluorine -18(18F)-DOPA, Pentetreotide, ACTH, Octreotide, Cushing's Syndrome, Ectopic Cushing Syndrome
Medical subject headings: Cushing Syndrome, Endocrine System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PentetreotideDrug
Also called [111In-diethylenetriaminepentaacetic acid-D-Phe]-pentetreotide
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.
18F-DOPADrug
Also called 6-fluoro-L-DOPA, 56494
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.
CT scanDevice
Also called computed tomography scan
CT scan of chest, abdomen, neck and /or pelvis
MRIDevice
Also called magnetic resonance imaging scan
MRI scan of head/pituitary, chest, abdomen, neck and /or pelvis
18-FDGDrug
Also called 18-fluorine fluorodeoxyglucose PET scan
FDG PET scan of body

Study groups in NCT00001849
Study group	Role	What they receive
Patients with Cushing Syndrome	Experimental	Patients receive various types of radiologic or nuclear medicine scans to identify tumor Receives: Drug: Pentetreotide; Drug: 18F-DOPA; Device: CT scan; Device: MRI; Drug: 18-FDG

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: six months or less

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 May 199926 Apr 2019

First posted4 Nov 1999 (estimated)
Study start20 May 1999
Primary completion26 Apr 2019
Study completion26 Apr 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Cushing SyndromeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Model description: Comparison of results in patients receiving similar imaging scans
Masking: None (open label)
Enrolment: 95 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00001849
Sponsor's protocol ID: 990055
Other IDs: 99-CH-0055
Status last verified: Jan 2020
First submitted: 3 Nov 1999
Last updated: 14 Apr 2021
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Findling JW, Tyrrell JB. Occult ectopic secretion of corticotropin. Arch Intern Med. 1986 May;146(5):929-33.
PubMed 3963984
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.
PubMed 2982290
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.
PubMed 1879062

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 14 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: New Imaging Modalities in the Evaluation of Patients With Ectopic Cushing's Syndrome
ClinicalTrials.gov ID: NCT00001849
Acronym / sponsor ID: 990055
Conditions: Cushing Syndrome, Endocrine Disease
Keywords: PET, fluorine -18(18F)-DOPA, Pentetreotide, ACTH, Octreotide, Cushing's Syndrome, Ectopic Cushing Syndrome
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 95 participants (actual)
Lead sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
Study start: 20 May 1999 (actual)
Primary completion: 26 Apr 2019 (actual)
Study completion: 26 Apr 2019 (actual)
First posted: 4 Nov 1999 (estimated)
Results: Posted 25 Jan 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Detailed description

Study design

Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Comparison of results in patients receiving similar imaging scans

Arm	Type	Receives
Patients with Cushing Syndrome	Experimental	Drug: Pentetreotide, Drug: 18F-DOPA, Device: CT scan, Device: MRI, Drug: 18-FDGPatients receive various types of radiologic or nuclear medicine scans to identify tumor

Who may qualify

Ages: 18 to 90 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

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.

Key exclusion criteria (11 listed)

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.
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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PentetreotideAlso: [111In-diethylenetriaminepentaacetic acid-D-Phe]-pentetreotideBinds 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.	Drug	Patients with Cushing Syndrome
18F-DOPAAlso: 6-fluoro-L-DOPA, 5649418F-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.	Drug	Patients with Cushing Syndrome
CT scanAlso: computed tomography scanCT scan of chest, abdomen, neck and /or pelvis	Device	Patients with Cushing Syndrome
MRIAlso: magnetic resonance imaging scanMRI scan of head/pituitary, chest, abdomen, neck and /or pelvis	Device	Patients with Cushing Syndrome
18-FDGAlso: 18-fluorine fluorodeoxyglucose PET scanFDG PET scan of body	Drug	Patients with Cushing Syndrome

Primary outcome

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.
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.

Results and safety

Results posted to the registry on 25 Jan 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Patients With Presumed Ectopic ACTH Secretion	68	54

Primary outcome: Sensitivity of Imaging Modalities for the Detection of ACTH-secreting Non-pituitary Tumor in Patients

Time frame: six months or less. Number (95% Confidence Interval). Unit: percentage of patients

Measure	CT Scan Results n = 54	Magnetic Resonance Imaging (MRI) Results n = 48	Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Results n = 9	[18F]-L-3,4-dihydroxyphenylalanine (18F-DOPA) PET Results n = 23	Standard Dose Pentetreotide Results n = 51	High Dose (18 mCi) Pentetreotide Results n = 21
Value	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)

Population analysed: Tumors identified by specific imaging modality in each patient

Primary outcome: Sensitivity of Imaging Modalities for the Detection of ACTH-secreting Non-pituitary Tumor in Specific Lesions

Time frame: six months or less. Number (95% Confidence Interval). Unit: percentage of lesions

Measure	CT Scan Results n = 54	MRI Results n = 48	FDG-PET Results n = 9	F-DOPA PET Results n = 23	Standard Dose Pentetreotide Results n = 51	High Dose (18 mCi) Octreotide Results n = 21
Value	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)

Population analysed: Tumors identified by specific imaging modality by lesions

Adverse events

Time frame: Adverse events (AEs) were monitored during each inpatient admission, generally 7 - 14 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Patients With Cushing Syndrome	0 of 65 (0%)	0 of 65 (0%)	4 of 68

Limitations and caveats (from the sponsor): Small number of subjects with this rare disorder; radiation safety risk limited number of some scans; difficulty in scheduling all scans due to lack of availability of slots or radionuclide.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 3963984Findling JW, Tyrrell JB. Occult ectopic secretion of corticotropin. Arch Intern Med. 1986 May;146(5):929-33.
Background: PubMed 2982290Jex 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.
Background: PubMed 1879062Trainer 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.
NIH Clinical Center Detailed Web PageLink provided by the sponsor.

Related trials for Cushing Syndrome

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Lynnette K Nieman, M.D. principal investigator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Sensitivity of Imaging Modalities for the Detection of ACTH-secreting Non-pituitary Tumor in Patients (time frame: six months or less). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00001849, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2021.