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

• ClinicalTrials.gov Identifier: NCT04569591
• Recruitment Status: Not yet recruiting
• First Posted: September 30, 2020
• Last Update Posted: March 11, 2022
• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cushing's Disease; Pituitary Adenoma	Drug: Acthrel	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Corticotrophin-Releasing Hormone (CRH) Stimulation for 18F-FDG-PET Detection of Pituitary Adenoma in Cushing's Disease
• Estimated Study Start Date: March 16, 2022
• Estimated Primary Completion Date: December 31, 2025
• Estimated Study Completion Date: December 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; patients aged 8 or older with Cushing's Disease who are surgical candidates for resection of ACTH producing pituitary adenoma within 12 weeks of PET imaging	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.

Outcome Measures

Primary Outcome Measures :

1. CRH-stimulated PET imaging demonstrates tumor in MRI-negative cases. [ Time Frame: Baseline ]
   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.

Secondary Outcome Measures :

1. Elevation of SUV of 18F-FDG [ Time Frame: Baseline ]
   To measure the elevation of SUV of 18F-FDG within adenomas compared to surrounding normal gland following CRH stimulated PET imaging.

Eligibility Criteria

• Ages Eligible for Study: 8 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Isaac J Pomeraniec, M.D.; (301) 496-2921; jonathan.pomeraniec@nih.gov

Locations

United States, Maryland

National Institutes of Health Clinical Center

Bethesda, Maryland, United States, 20892

Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 prpl@cc.nih.gov

Sponsors and Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Prashant Chittiboina, M.D.; National Institute of Neurological Disorders and Stroke (NINDS)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

• Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
• ClinicalTrials.gov Identifier: NCT04569591
• Other Study ID Numbers: 200048; 20-N-0048
• First Posted: September 30, 2020
• Last Update Posted: March 11, 2022
• Last Verified: August 6, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):

Corticotropinoma; Pituitary Microadenoma; Acthrel

Additional relevant MeSH terms:

Adenoma; Pituitary Neoplasms; ACTH-Secreting Pituitary Adenoma; Pituitary Diseases; Pituitary ACTH Hypersecretion; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Hyperpituitarism