ACTHPhase 2NCT02019706
Prospective Evaluation of 68Ga-DOTATATE PET/CT, Octreotide and F-DOPA PET Imaging in Ectopic Cushing Syndrome
A Phase 2 study testing DOTATATE PET-CT, F-DOPA PET CT and CT scan in people with ACTH and Cushing's Syndrome, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
Between 10% and 15% of patients with endogenous hypercortisolism (Cushing syndrome) have ectopic (non-pituitary) production of adrenocorticotropin hormone (ACTH) that causes cortisol excess. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- ACTH, Cushing's Syndrome
- What is being tested?
- DOTATATE PET-CT, F-DOPA PET CT and CT scan
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Feb 2014to 31 Dec 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be eligible to participate in this study, an individual must meet all of the following criteria:
- 18 - 90 years of age
- Medical history of ectopic Cushing syndrome or diagnosed with the possibility of ectopic Cushing syndrome
- For females of reproductive potential: agreement to use highly effective contraception for at least 2 weeks before any PET scan
- Ability of subject to understand and the willingness to sign a written informed consent document
- Stated willingness to comply with all study procedures and availability for the duration of the study
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Pregnancy or lactation; the radiation associated with PET and CT scans may be harmful to a developing fetus. Likewise the ingestion of radionuclides in breast milk has an unknown risk to an infant.
- Evidence of severe active infection
- Clinically significantly impaired cardiovascular function, abnormal coagulation in the absence of medically-indicated treatment (PT and PTT elevated by 30% above the normal values), hematopoietic (hematocrit less than 30%, hemoglobin below 10 g/dl, white count below 3000 K/UL, and platelets below 100,000 K/mm^3), hepatic (liver enzymes elevated by 4-fold above normal values), or renal function (plasma creatinine level over 2.1).
- Based on the clinical judgment of the attending physician, other medical problems may prompt exclusion.
- 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 greater than 450 ml.
- Subjects who previously underwent ten or more F-DOPA PET/CT scans and ten or more DOTATATE scans.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Between 10% and 15% of patients with endogenous hypercortisolism (Cushing syndrome) have ectopic (non-pituitary) production of adrenocorticotropin hormone (ACTH) that causes cortisol excess. In approximately 50% of these patients, the tumoral source of ACTH cannot be found initially despite very detailed and extensive imaging, including studies such as computed tomography, magnetic resonance imaging, and octreotide scan (Octreoscan) using the standard dose of indium- 111 pentetreotide ([111In-DTPA-D-Phe]-pentetreotide). The sensitivity and specificity of structurally based imaging studies depends on anatomic alterations and the size of the tumor. In contrast, positron emission tomography (PET) and somatostatin ligand imaging detect pathologic tissue based on physiologic and biochemical processes within the abnormal tissue. This protocol tests the ability of [18F]-L-3,4-dihydroxyphenylalanine (18F-DOPA) PET, and the somatostatin imaging analogue, 68Ga-DOTATATE-PET, to localize the source of ectopic ACTH production.
Read the detailed description
Study Description:
Between 10% and 15% of patients with endogenous hypercortisolism (Cushing syndrome) have ectopic (non-pituitary) production of adrenocorticotropin hormone (ACTH) that causes cortisol excess. In approximately 50% of these patients, the tumoral source of ACTH cannot be found initially despite very detailed and extensive imaging, including studies such as computed tomography, magnetic resonance imaging, and octreotide scan (Octreoscan) using the standard dose of indium- 111 pentetreotide ([111In-DTPA-D-Phe]-pentetreotide). The sensitivity and specificity of structurally based imaging studies depends on anatomic alterations and the size of the tumor. In contrast, positron emission tomography (PET) and somatostatin ligand imaging detect pathologic tissue based on physiologic and biochemical processes within the abnormal tissue.
This protocol tests the ability of [18F]-L-3,4-dihydroxyphenylalanine (18F-DOPA) PET, and the somatostatin imaging analogue, 68Ga-DOTATATE-PET, to localize the source of ectopic ACTH production.
Objectives:
Primary Objectives:
- To determine which imaging technique (F-DOPA PET/CT, 68Ga-DOTATATE PET/CT, standard CT, and/or standard MRI) has the best sensitivity.
- To determine if there is a combination of imaging tests with optimal diagnostic accuracy.
Secondary Objective:
-To evaluate a potential correlation between 18F-DOPA or 68Ga-DOTATATE uptake and the type of tumor, its size, SSTR expression or proliferative activity.
Exploratory Objectives:
- To evaluate the ability of gated cardiac imaging with CT and MRI to improve the detection of retrocardiac lung lesions.
- To determine whether PET scans at an interval of less than one year localize tumors.
Endpoints:
Primary Endpoint:
-Imaging results and pathology of resected tumors
Secondary Endpoints:
-18F-DOPA or 68Ga-DOTATATE imaging results, tumor pathology, tumor size, proliferative index and SSTR expression.
Exploratory Endpoints:
- Gated cardiac imaging CT and/or MRI; all other imaging results, tumor pathology.
- Imaging results and pathology of resected tumors.
- Conditions
- ACTH, Cushing's Syndrome
- Being tested
- DOTATATE PET-CT, F-DOPA PET CT, CT scan, Routine MRI scan, Gated MRI scan
- Keywords
- DOTATATE, Cushing's Syndrome, Hypercortisolism
- Medical subject headings
- Cushing Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DOTATATE PET-CTRadiation
68Ga-DOTATATE PET/CT
F-DOPA PET CTRadiation
68Ga-DOTATATE PET/CT
CT scanRadiation
routine CT scan
Routine MRI scanDiagnostic test
routine 1.5 or 3T MRI scan
Gated MRI scanDiagnostic test
Cardiac gated MRI scan
68Ga-DOTATATEDrug
68Ga-DOTATATE radioligand
18F-DOPADrug
18F-DOPA radioligand
| Study group | Role | What they receive |
|---|---|---|
| Imaging | Experimental | All subjects will be imaged Receives: Radiation: DOTATATE PET-CT; Radiation: F-DOPA PET CT; Radiation: CT scan; Diagnostic Test: Routine MRI scan; Diagnostic Test: Gated MRI scan; Drug: 68Ga-DOTATATE; Drug: 18F-DOPA |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine which imaging technique (F-DOPA PET/CT, 68Ga-DOTATATE PET/CT, CT, and/or MRI) has the best sensitivity.
Subjects will be imaged every 6-12 months until tumor is found
Measured: 6-12 months
To determine if there is a combination of imaging tests with optimal diagnostic accuracy.
subjects will be imaged every 6-12 months until tumor is found
Measured: 6-12 months
Secondary outcomes (1)
To evaluate a potential correlation between 18F-DOPA or 68Ga-DOTATATE uptake and the type of tumor, its size, SSTR expression or proliferative activity.
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2013 (estimated)
- Study start12 Feb 2014
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ACTHStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- 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
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Lynnette K Nieman, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02019706
- Sponsor's protocol ID
- 140028
- Other IDs
- 14-CH-0028
- Status last verified
- 8 May 2026
- First submitted
- 21 Dec 2013
- Last updated
- 2 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: On request, IPD related to a publication will be made available.
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Evaluation of 68Ga-DOTATATE PET/CT, Octreotide and F-DOPA PET Imaging in Ectopic Cushing Syndrome
- ClinicalTrials.gov ID
- NCT02019706
- Acronym / sponsor ID
- 140028
- Conditions
- ACTH, Cushing's Syndrome
- Keywords
- DOTATATE, Cushing's Syndrome, Hypercortisolism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 12 Feb 2014 (actual)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 24 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Between 10% and 15% of patients with endogenous hypercortisolism (Cushing syndrome) have ectopic (non-pituitary) production of adrenocorticotropin hormone (ACTH) that causes cortisol excess. In approximately 50% of these patients, the tumoral source of ACTH cannot be found initially despite very detailed and extensive imaging, including studies such as computed tomography, magnetic resonance imaging, and octreotide scan (Octreoscan) using the standard dose of indium- 111 pentetreotide ([111In-DTPA-D-Phe]-pentetreotide). The sensitivity and specificity of structurally based imaging studies depends on anatomic alterations and the size of the tumor. In contrast, positron emission tomography (PET) and somatostatin ligand imaging detect pathologic tissue based on physiologic and biochemical processes within the abnormal tissue. This protocol tests the ability of [18F]-L-3,4-dihydroxyphenylalanine (18F-DOPA) PET, and the somatostatin imaging analogue, 68Ga-DOTATATE-PET, to localize the source of ectopic ACTH production.
Detailed description
Study Description:
Between 10% and 15% of patients with endogenous hypercortisolism (Cushing syndrome) have ectopic (non-pituitary) production of adrenocorticotropin hormone (ACTH) that causes cortisol excess. In approximately 50% of these patients, the tumoral source of ACTH cannot be found initially despite very detailed and extensive imaging, including studies such as computed tomography, magnetic resonance imaging, and octreotide scan (Octreoscan) using the standard dose of indium- 111 pentetreotide ([111In-DTPA-D-Phe]-pentetreotide). The sensitivity and specificity of structurally based imaging studies depends on anatomic alterations and the size of the tumor. In contrast, positron emission tomography (PET) and somatostatin ligand imaging detect pathologic tissue based on physiologic and biochemical processes within the abnormal tissue.
This protocol tests the ability of [18F]-L-3,4-dihydroxyphenylalanine (18F-DOPA) PET, and the somatostatin imaging analogue, 68Ga-DOTATATE-PET, to localize the source of ectopic ACTH production.
Objectives:
Primary Objectives:
- To determine which imaging technique (F-DOPA PET/CT, 68Ga-DOTATATE PET/CT, standard CT, and/or standard MRI) has the best sensitivity.
- To determine if there is a combination of imaging tests with optimal diagnostic accuracy.
Secondary Objective:
-To evaluate a potential correlation between 18F-DOPA or 68Ga-DOTATATE uptake and the type of tumor, its size, SSTR expression or proliferative activity.
Exploratory Objectives:
- To evaluate the ability of gated cardiac imaging with CT and MRI to improve the detection of retrocardiac lung lesions.
- To determine whether PET scans at an interval of less than one year localize tumors.
Endpoints:
Primary Endpoint:
-Imaging results and pathology of resected tumors
Secondary Endpoints:
-18F-DOPA or 68Ga-DOTATATE imaging results, tumor pathology, tumor size, proliferative index and SSTR expression.
Exploratory Endpoints:
- Gated cardiac imaging CT and/or MRI; all other imaging results, tumor pathology.
- Imaging results and pathology of resected tumors.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Imaging | Experimental | Radiation: DOTATATE PET-CT, Radiation: F-DOPA PET CT, Radiation: CT scan, Diagnostic Test: Routine MRI scan, Diagnostic Test: Gated MRI scan, Drug: 68Ga-DOTATATE, Drug: 18F-DOPAAll subjects will be imaged |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- To be eligible to participate in this study, an individual must meet all of the following criteria:
- 18 - 90 years of age
- Medical history of ectopic Cushing syndrome or diagnosed with the possibility of ectopic Cushing syndrome
- For females of reproductive potential: agreement to use highly effective contraception for at least 2 weeks before any PET scan
- Ability of subject to understand and the willingness to sign a written informed consent document
Key exclusion criteria (8 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Pregnancy or lactation; the radiation associated with PET and CT scans may be harmful to a developing fetus. Likewise the ingestion of radionuclides in breast milk has an unknown risk to an infant.
- Evidence of severe active infection
- Clinically significantly impaired cardiovascular function, abnormal coagulation in the absence of medically-indicated treatment (PT and PTT elevated by 30% above the normal values), hematopoietic (hematocrit less than 30%, hemoglobin below 10 g/dl, white count below 3000 K/UL, and platelets below 100,000 K/mm^3), hepatic (liver enzymes elevated by 4-fold above normal values), or renal function (plasma creatinine level over 2.1).
- Based on the clinical judgment of the attending physician, other medical problems may prompt exclusion.
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 |
|---|---|---|
| DOTATATE PET-CT68Ga-DOTATATE PET/CT | Radiation | Imaging |
| F-DOPA PET CT68Ga-DOTATATE PET/CT | Radiation | Imaging |
| CT scanroutine CT scan | Radiation | Imaging |
| Routine MRI scanroutine 1.5 or 3T MRI scan | Diagnostic test | Imaging |
| Gated MRI scanCardiac gated MRI scan | Diagnostic test | Imaging |
| 68Ga-DOTATATE68Ga-DOTATATE radioligand | Drug | Imaging |
| 18F-DOPA18F-DOPA radioligand | Drug | Imaging |
Primary outcome
To determine which imaging technique (F-DOPA PET/CT, 68Ga-DOTATATE PET/CT, CT, and/or MRI) has the best sensitivity.
Time frame: 6-12 months
Subjects will be imaged every 6-12 months until tumor is found
To determine if there is a combination of imaging tests with optimal diagnostic accuracy.
Time frame: 6-12 months
subjects will be imaged every 6-12 months until tumor is found
1 secondary outcome
To evaluate a potential correlation between 18F-DOPA or 68Ga-DOTATATE uptake and the type of tumor, its size, SSTR expression or proliferative activity.
Time frame: Ongoing
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. On request, IPD related to a publication will be made available.
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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.
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?
A Phase 2 study testing DOTATATE PET-CT, F-DOPA PET CT and CT scan in people with ACTH and Cushing's Syndrome, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
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 6 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 2 Oct 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Raven N McGlotten, R.N. ((301) 827-0190, mcglottenr@mail.nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine which imaging technique (F-DOPA PET/CT, 68Ga-DOTATATE PET/CT, CT, and/or MRI) has the best sensitivity. (time frame: 6-12 months). 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?
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 2 Oct 2026.