CRH Stimulation for Cushing's Disease

Overseen By Prashant Chittiboina, M.D.

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

Disqualifiers: Pregnancy, Renal insufficiency, High glucose, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if administering a hormone called CRH before a PET scan can help detect pituitary gland tumors that cause Cushing's disease. These tumors can lead to obesity, diabetes, and high blood pressure. The trial seeks individuals with Cushing's disease whose tumors are not clearly visible on an MRI. Participants must plan to undergo surgery to remove their tumor within three months after the scan. This research could enhance imaging techniques for diagnosing Cushing's disease in the future. As an unphased trial, it offers participants the opportunity to contribute to innovative imaging techniques that could improve future diagnosis and treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this protocol is safe for detecting pituitary gland tumors?

Research has shown that CRH, a hormone, can help identify pituitary gland tumors in people with Cushing's disease. This hormone, part of the body's stress response, can make certain tumors more visible during scans.

Studies have found that CRH stimulation is generally well-tolerated by patients. It increases certain hormones in the body, aiding doctors in detecting tumors that might not be visible with other methods. No significant side effects have been reported in studies specifically related to using CRH for tumor detection.

CRH is not a new treatment; it has been used in various diagnostic tests before, indicating its reasonable safety, especially since it is used here for a similar purpose. Current evidence suggests that CRH is safe for use in these tests. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Acthrel is unique because it focuses on stimulating the body's natural hormone pathways to address Cushing's Disease. Unlike standard treatments that often rely on surgery or medications that inhibit cortisol production, Acthrel works by stimulating the release of corticotropin-releasing hormone (CRH). This approach could offer a more targeted method to manage hormone levels and potentially improve the effectiveness of surgical outcomes. Researchers are excited because this could mean less invasive and more precise treatment options for patients, especially those preparing for surgery.

What evidence suggests that giving CRH before a PET scan is effective for finding pituitary tumors in Cushing's disease?

In this trial, participants will undergo the CRH stimulation test, which previous studies have shown to effectively detect pituitary tumors causing Cushing's disease. The test demonstrated 100% sensitivity, correctly identifying all cases in the study. This method uses the hormone CRH to enhance tumor visibility during brain scans, aiming to detect tumors that standard MRI scans might miss. Early research suggests that administering CRH before a PET scan could improve the detection of these hidden tumors, leading to more accurate treatment planning. ^{6 7 8 9 10}

Who Is on the Research Team?

Prashant Chittiboina, M.D.

Principal Investigator

National Institute of Neurological Disorders and Stroke (NINDS)

Are You a Good Fit for This Trial?

This trial is for people aged 8 or older with Cushing's disease from a pituitary tumor, which isn't clearly visible on MRI. They must be able to have a PET scan without anesthesia and give consent (parents/guardians for minors). Candidates should be ready for surgery within three months after the scan and have normal liver function.

Inclusion Criteria

Ability to provide informed consent for study participation (parents or guardians in the case of minors)

I am 8 or older with Cushing's disease and my MRI might show a tumor in the pituitary gland.

I am scheduled for surgery to remove a tumor in my pituitary gland within 1 week after a PET scan.

Exclusion Criteria

You have a known intolerance to CRH.

Your blood sugar level is higher than 200 mg/dL before the scan with 18F-FDG.

I have severe kidney issues or had a liver transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

CRH Stimulation and PET Imaging

Participants receive CRH stimulation followed by 18F-FDG PET imaging to detect MRI-negative pituitary adenomas

1 day

1 visit (in-person)

Surgery

Participants undergo surgical resection of the pituitary adenoma within 12 weeks after PET imaging

Within 12 weeks

Follow-up

Participants continue regular follow-up in the clinic to monitor recovery and treatment effectiveness

Ongoing

What Are the Treatments Tested in This Trial?

Interventions

• Acthrel

Trial Overview The study tests if CRH hormone given before a PET brain scan can better detect pituitary tumors in Cushing's disease patients. Participants will receive an injection of radioactive sugar and CRH, followed by imaging inside a scanner.

How Is the Trial Designed?

Group I: 1 Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

National Institute of Neurological Disorders and Stroke (NINDS)

Lead Sponsor

Trials

1,403

Recruited

655,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6711639/

RELIABILITY OF THE CORTICOTROPIN RELEASING ... The CRH stimulation test had a sensitivity and specificity of 100% and 8%, and positive and negative predictive values of 100% and 45% according to the current ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12193485/

Outcomes of the Transsphenoidal Approach for ACTH ... Our findings demonstrate that ACTH, postoperative serum cortisol, and urinary free cortisol are valuable predictors of relapse over a five-year period.

3. withpower.com withpower.com/trial/phase-pituitary-acth-hypersecretion-9-2021-a46dd

CRH Stimulation for Cushing's Disease · Info for Participants Trial Overview The study tests if CRH hormone given before a PET brain scan can better detect pituitary tumors in Cushing's disease patients. Participants will ...

4. researchgate.net researchgate.net/figure/Diagnostic-outcome-of-ACTH-during-the-CRH-stimulation-test_tbl1_364201949

Diagnostic outcome of ACTH during the CRH stimulation test. In the postoperative CRH test, plasma ACTH levels showed six-fold increase. The postoperative DST showed cortisol suppression at 0.5 mg of DEX. The UFC levels ...

5. academic.oup.com academic.oup.com/jcem/article/83/1/63/2865075

Outcomes of Therapy for Cushing's Disease due to ... We reviewed our experience with 21 patients who had Cushing's disease due to ACTH-secreting macroadenomas to clarify the natural history of this disease. A.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8743006/

Consensus on Diagnosis and Management of Cushing's ... Accordingly, desmopressin and CRH stimulation testing have proven useful in distinguishing between pituitary and ectopic tumors. Increased plasma ACTH and ...

7. ese-hormones.org ese-hormones.org/media/2jkhzxtb/crh-shortage-recommendation.pdf

ESE Recommendation on CRH Shortage As. ACTH-secreting pituitary tumours can express aberrant V3 vasopressin receptors, desmopressin infusion may stimulate ACTH secretion from these cells (16).

8. sciencedirect.com sciencedirect.com/science/article/pii/S2772529422000583

Update in Cushing disease: What the neurosurgeon has to ... A positive response to CRH stimulation is set arbitrarily at a 50% or more increase in ACTH and 20% or more increase in cortisol (Lonser et al., 2017). 3.3.

9. e-apem.org e-apem.org/journal/view.php?number=645

A patient with Cushing disease lateralizing a pituitary ... Our case suggests that desmopressin use instead of CRH to stimulate ACTH in pediatric patients may be safe and effective. IPSS can be a valuable ...

10. thejns.org thejns.org/view/journals/j-neurosurg/126/2/article-p404.xml

Cushing's disease: pathobiology, diagnosis, and management ... Cushing's disease (CD) is the result of excess secretion of adrenocorticotropic hormone (ACTH) by a benign monoclonal pituitary adenoma.