Clinical trial NCT04569591: Corticotrophin-releasing Hormone (CRH) Stimulation for 18F-FDG-PET Detection of Pituitary Adenoma in Cushing s Disease
Official title: Corticotrophin-Releasing Hormone (CRH) Stimulation for 18F-FDG-PET Detection of Pituitary Adenoma in Cushing's Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Cushing's Disease
Pituitary Adenoma
Keywords: Corticotropinoma
Pituitary Microadenoma
Acthrel
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2020-09-30
Enrollment: 22
Sex: ALL
Minimum age (years): 8
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Background:

Cushing s disease is caused by a pituitary gland tumor. Patients with Cushing s disease suffer obesity, diabetes, osteoporosis, weakness, and hypertension. The cure is surgery to remove the pituitary tumor. Currently, MRI is the best way to find these tumors. But not all tumors can be seen with an MRI. Researchers hope giving the hormone CRH before a PET scan can help make these tumors more visible.

Objective:

To test whether giving CRH before a PET scan will help find pituitary gland tumors that might be causing Cushing s disease.

Eligibility:

People ages 8 and older with Cushing s disease that is caused by a pituitary gland tumor that cannot be reliably seen on MRI

Design:

Participants will be screened with their medical history, a physical exam, an MRI, and blood tests.

Participants will have at least one hospital visit. During their time in the hospital, they will have a physical exam and a neurological exam. They will have a PET scan of the brain. A thin plastic tube will be inserted into an arm vein. A small amount of radioactive sugar and CRH will be injected through the tube. Participants will lie in a darkened room for about an hour and be asked to urinate. Then they will lie inside the scanner for about 40 minutes. After the scan, they will be asked to urinate every 2-3 hours for the rest of the day. Blood will be drawn through a needle in the arm.

Participants will have surgery to remove their tumor within 3 months after the scan.

Participants will then continue regular follow-up in the clinic.

Detailed description: This study is designed as a single institution trial. The study utilizes safe and clinically-validated tools for preoperative workup of patients with small pituitary tumors. CRH stimulation and 18F-FDG uptake in PET imaging will be used to detect MRI-negative pituitary adenomas in patients with Cushing s disease. Patients who have MRI-negative pituitary microadenomas will undergo 18F-FDG PET-imaging with CRH stimulation. Intravenous 18F-FDG will be given approximately four hours following CRH administration. Within 12 weeks after completion of the last 18F-FDG high-resolution PET-imaging scan, patients will undergo surgical resection of the pituitary adenoma. Surgical and histological confirmation of adenoma location will be noted. All images will be read independently by neuroradiologists blinded to clinical and histopathological outcomes. The diagnostic and localization accuracy of PET-imaging will be assessed by comparing the PET findings with histopathology.

Eligibility criteria: * INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Patients aged 8 or older with biochemical evidence of Cushing s disease and a clinical MRI pituitary neuroradiology result of negative or possible adenoma (e.g. 'no tumor' or 'possible tumor' around)
2. MRI of the Pituitary gland with and without contrast obtained within 9 months of screening
3. Ability to undergo PET-imaging without general anesthesia
4. Ability to provide informed consent for study participation (parents or guardians in the case of minors)
5. Clinical diagnosis of Cushing s disease based on documented medical records
6. Surgical candidate for resection of ACTH producing pituitary adenoma within 1 weeks of PET-imaging
7. Normal liver function as evidenced by liver enzyme tests completed within 14 days before injection of radiopharmaceutical: SGOT, SGPT \<= 5 x upper limit of normal; bilirubin \<= 2 x upper limit of normal
8. Enrolled in 03-N-0164, Evaluation of Neurosurgical Disorders.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Pregnancy or lactation
2. Severe chronic renal insufficiency (glomerular filtration rate \< 30 mL/min/1.73 m squared), hepatorenal syndrome or post-liver transplantation.
3. Elevated blood glucose level above 200 mg/dL on the day of the scan prior to 18F-FDG administration.
4. Known intolerance to CRH

INCLUSION OF VULNERABLE PARTICIPANTS:

* Children: Children age 8 and older are included in this protocol. More than half of the patients with CD requiring transsphenoidal surgery at the NIH are children. Furthermore, the knowledge gained by the use of CRH PET imaging in children with MR-invisible tumors will provide direct benefit to the individual child and will provide generalizable knowledge in the treatment of CD in this population. Children under the age of 8 usually require anesthesia for a PET scan, which involves greater risk. Therefore, children under the age of 8 will be excluded from participation.
* NIH Employees: Protections for employees and staff participating in this study include:

  1) assuring that the participation or refusal to participate will have no effect, either beneficial or adverse, on the subject s employment or position at the NIH, 2) giving employees and staff who are interested in participating the 'NIH Information Sheet on Employee Research Participation' prior to obtaining consent, and 3) assuring that there will be no direct solicitation of employees or staff. 4) Independent consent monitoring will be provided by the NIH HSPU. 5) The PI will train study staff regarding obtaining and handling potentially sensitive and private information about co-workers through staff discussions and written branch/section procedures. No compensation will be provided for this protocol.
* Pregnant or lactating women: Pregnant and lactating women will be excluded from participation. The PET radiopharmaceutical used in this study can be harmful to a developing fetus. Therefore women who are able to become pregnant will have a pregnancy test performed within 24 hours before PET-imaging. Individuals will not be able to participate in PET scanning if the pregnancy test results positive.

Primary outcomes:
measure: CRH-stimulated PET imaging demonstrates tumor in MRI-negative cases.
timeFrame: Baseline
Secondary outcomes:
measure: Elevation of SUV of 18F-FDG
timeFrame: Baseline
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institute of Neurological Disorders and Stroke (NINDS)
name: Prashant Chittiboina, M.D.
role: PRINCIPAL_INVESTIGATOR
References: