Corticotrophin-releasing Hormone (CRH) Stimulation for 18F-FDG-PET Detection of Pituitary Adenoma in Cushing s Disease

Pituitary Adenoma Clinical Trial

Official title:

Corticotrophin-Releasing Hormone (CRH) Stimulation for 18F-FDG-PET Detection of Pituitary Adenoma in Cushing's Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04569591
• Other study ID #: 200048
• Secondary ID: 20-N-0048
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 5, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: September 12, 2023
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Isaac J Pomeraniec, M.D.
• Phone: (301) 496-2921
• Email: jonathan.pomeraniec[@]nih.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 22
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years and older

Eligibility

• 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.

Related Conditions & MeSH terms

• ACTH-Secreting Pituitary Adenoma
• Adenoma
• Cushing's Disease
• Pituitary ACTH Hypersecretion
• Pituitary Adenoma
• Pituitary Diseases
• Pituitary Neoplasms

Intervention

Drug:
• Acthrel
Intravenous administration of ovine CRH (Acthrel (Registered Trademark) 1 mcg/kg up to a maximum dose of 100 mcg) results in selective increase in ACTH activity of pituitary adenomas within two minutes and peaks between 10-15 minutes.

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CRH-stimulated PET imaging demonstrates tumor in MRI-negative cases.	The primary outcome measure will be defined as whether or not CRH- stimulated PET imaging demonstrates tumor in MRI-negative cases. This will be demonstrated by assessing the accuracy and sensitivity of 18F-FDG high-resolution PET-imaging detection of ACTH-adenomas that could not be reliably detected on MR-imaging. Measures will include determining the rate of true tumor detection using PET-imaging compared to histologically-confirmed tumor location.	Baseline
Secondary	Elevation of SUV of 18F-FDG	To measure the elevation of SUV of 18F-FDG within adenomas compared to surrounding normal gland following CRH stimulated PET imaging.	Baseline

External Links

•   NIH Clinical Center Detailed Web Page