Osilodrostat Therapy and 11C-methionine PET to Improve Corticotroph Adenoma Detection

NCT06701838 | Not Yet Recruiting

• 1 other identifier: 24/EM/0178
• Study Type: observational
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief Summary

Cushing's disease is a rare condition where the body produces too much of a hormone called cortisol. Cortisol helps with metabolism, the immune system, and managing stress. But too much cortisol can lead to problems like weight gain, high blood pressure, diabetes, and changes in appearance, such as a round face or a hump on the back. People with Cushing's disease often gain weight around their belly and may get stretch marks. They might also feel emotional changes, tiredness, or weakness. This disease is usually caused by a small, non-cancerous growth in the pituitary gland called a 'pituitary adenoma.' The pituitary gland is a small organ at the base of the brain and controls many important functions. When someone is diagnosed with Cushing's disease, doctors typically use an MRI scan to look for the adenoma in the pituitary gland. If found, the adenoma can often be removed through surgery, which often cures the disease. This is the standard treatment for patients with Cushing's disease. However, MRIs only find the adenoma in about 60% of the time. If surgery isn't possible because the adenoma can't be located, doctors may use medication to lower cortisol levels. In addition to the MRI, doctors might use a special PET/CT scan to find the adenoma. This PET/CT scan is not available everywhere, so the investigators refer our patients to Cambridge Hospital for this scan, which uses a special dye called 11C-methionine. The investigators then review the scan with the teams from Imperial and Cambridge. If the PET/CT scan shows where the adenoma is, the patient will be offered surgery. However, finding the adenoma can be challenging because they are often small and hard to distinguish from normal tissue. If the adenoma isn't visible, the investigators will use medical treatment to lower cortisol. After a period of medical treatment, another MRI scan and PET/CT scan will be done to see if the adenoma has become clearer. This second PET/CT scan would not normally be part of routine clinical care. The investigators will then compare the results of the two scans to see if the special dye is showing a stronger signal, which can help us find the adenoma more accurately and improve the chance of curing Cushing's disease with surgery.

Conditions

Cushing's Disease; Hypercortisolism; Pituitary Adenoma; Pituitary ACTH Secreting Adenoma

Keywords

Cushing's disease; Osilodrostat; 11C-methionine PET; Corticotroph adenoma

Outcome Measures

Primary Outcomes (1)

• Tumour activity on functional imaging

  Change in 11C-methionine SUVmax in a corticotroph adenoma through comparison of pre- and post-osilodrostat 11C-methionine PET/CT

  Following 3-month period of eucortisolaemia

Secondary Outcomes (1)

• Radiological tumour appearance

  Following a 3-month period of eucortisolaemia.

Interventions

11C-Methionine PET/CT DIAGNOSTIC_TEST

After a 3-month period of eucortisolaemia, patients will undergo a second MRI of the pituitary gland and 11C-methionine PET/CT scan with SUVmax ratio analysis of the presumed corticotroph pituitary adenoma.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Following confirmation of eligibility patient's will be discussed at a pre-enrolment MDT before recruitment.

You may qualify if:

• age 18 years and older newly diagnosed with Cushing's disease and no/ an equivocal surgical target on MRI pituitary or
• age 18 years and older and previously undergone pituitary surgery for Cushing's disease and clinical and biochemical evidence of persistent/ recurrent hypercortisolaemia and no/ an equivocal surgical target on MRI pituitary.

You may not qualify if:

• Absolute contraindication to osilodrostat therapy and/or 11C methionine PET.
• Pregnancy or unwillingness to use secure contraception for the study duration (female participants only).
• Unable to comply with study visit schedule.

Sponsors & Collaborators

• Imperial College London: lead
• University of Cambridge: collaborator

Related Publications (11)

• Gillett D, Senanayake R, MacFarlane J, van der Meulen M, Koulouri O, Powlson AS, Crawford R, Gillett B, Bird N, Heard S, Kolias A, Mannion R, Aloj L, Mendichovszky IA, Cheow H, Bashari WA, Gurnell M. Localization of TSH-secreting pituitary adenoma using 11C-methionine image subtraction. EJNMMI Res. 2022 May 7;12(1):26. doi: 10.1186/s13550-022-00899-7.

  PMID: 35524902 BACKGROUND

• Bashari WA, van der Meulen M, MacFarlane J, Gillett D, Senanayake R, Serban L, Powlson AS, Brooke AM, Scoffings DJ, Jones J, O'Donovan DG, Tysome J, Santarius T, Donnelly N, Boros I, Aigbirhio F, Jefferies S, Cheow HK, Mendichovszky IA, Kolias AG, Mannion R, Koulouri O, Gurnell M. 11C-methionine PET aids localization of microprolactinomas in patients with intolerance or resistance to dopamine agonist therapy. Pituitary. 2022 Aug;25(4):573-586. doi: 10.1007/s11102-022-01229-9. Epub 2022 May 24.

  PMID: 35608811 BACKGROUND

• Bashari WA, Gillett D, MacFarlane J, Powlson AS, Kolias AG, Mannion R, Scoffings DJ, Mendichovszky IA, Jones J, Cheow HK, Koulouri O, Gurnell M. Modern imaging in Cushing's disease. Pituitary. 2022 Oct;25(5):709-712. doi: 10.1007/s11102-022-01236-w. Epub 2022 Jun 6.

  PMID: 35666391 BACKGROUND

• Lonser RR, Nieman L, Oldfield EH. Cushing's disease: pathobiology, diagnosis, and management. J Neurosurg. 2017 Feb;126(2):404-417. doi: 10.3171/2016.1.JNS152119. Epub 2016 Apr 22.

  PMID: 27104844 BACKGROUND

• Gadelha M, Bex M, Feelders RA, Heaney AP, Auchus RJ, Gilis-Januszewska A, Witek P, Belaya Z, Yu Y, Liao Z, Ku CHC, Carvalho D, Roughton M, Wojna J, Pedroncelli AM, Snyder PJ. Randomized Trial of Osilodrostat for the Treatment of Cushing Disease. J Clin Endocrinol Metab. 2022 Jun 16;107(7):e2882-e2895. doi: 10.1210/clinem/dgac178.

  PMID: 35325149 BACKGROUND

• Biller BM, Grossman AB, Stewart PM, Melmed S, Bertagna X, Bertherat J, Buchfelder M, Colao A, Hermus AR, Hofland LJ, Klibanski A, Lacroix A, Lindsay JR, Newell-Price J, Nieman LK, Petersenn S, Sonino N, Stalla GK, Swearingen B, Vance ML, Wass JA, Boscaro M. Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab. 2008 Jul;93(7):2454-62. doi: 10.1210/jc.2007-2734. Epub 2008 Apr 15.

  PMID: 18413427 BACKGROUND

• Wang B, Zheng S, Ren J, Zhong Z, Jiang H, Sun Q, Su T, Wang W, Sun Y, Bian L. Reoperation for Recurrent and Persistent Cushing's Disease without Visible MRI Findings. J Clin Med. 2022 Nov 20;11(22):6848. doi: 10.3390/jcm11226848.

  PMID: 36431325 BACKGROUND

• Tritos NA, Biller BMK. Current management of Cushing's disease. J Intern Med. 2019 Nov;286(5):526-541. doi: 10.1111/joim.12975. Epub 2019 Oct 4.

  PMID: 31512305 BACKGROUND

• Pivonello R, De Martino MC, De Leo M, Simeoli C, Colao A. Cushing's disease: the burden of illness. Endocrine. 2017 Apr;56(1):10-18. doi: 10.1007/s12020-016-0984-8. Epub 2016 May 17.

  PMID: 27189147 BACKGROUND

• Pecori Giraldi F, Moro M, Cavagnini F; Study Group on the Hypothalamo-Pituitary-Adrenal Axis of the Italian Society of Endocrinology. Gender-related differences in the presentation and course of Cushing's disease. J Clin Endocrinol Metab. 2003 Apr;88(4):1554-8. doi: 10.1210/jc.2002-021518.

  PMID: 12679438 BACKGROUND

• Nishioka H, Yamada S. Cushing's Disease. J Clin Med. 2019 Nov 12;8(11):1951. doi: 10.3390/jcm8111951.

  PMID: 31726770 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples, pituitary tissue

MeSH Terms

Conditions

Cushing Syndrome; Pituitary Neoplasms; Pituitary ACTH Hypersecretion; ACTH-Secreting Pituitary Adenoma

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypothalamic Diseases; Pituitary Diseases; Hyperpituitarism; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Central Study Contacts

Florian Wernig, MD FRCP

CONTACT

+44 7939812122; fwernig@ic.ac.uk

Zin Htut

CONTACT

zin.htut23@ic.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2024
• First Posted: November 22, 2024
• Study Start: December 3, 2024
• Primary Completion (Estimated): July 5, 2026
• Study Completion (Estimated): July 5, 2026
• Last Updated: December 3, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share