Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06440122
Other study ID # GafREC-Endo203
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date May 31, 2024
Est. completion date December 31, 2024

Study information

Verified date May 2024
Source King's College Hospital NHS Trust
Contact Georgios K Dimitriadis
Phone 0777615084
Email g.dimitriadis@nhs.net
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

White adipose tissue (WAT) and brown adipose tissue (BAT) form the main adipose tissue subtypes in humans and several animals. BAT, owing to its unique metabolic function, has been of increased focus and interest in metabolic research (1). BAT forms the major organ of non-shivering thermogenesis in the body, and is dependent on the large concentration of mitochondria and increased uncoupling protein-1 (UCP-1) activity present in this type of tissue (2). There are numerous triggers for the metabolic activation of BAT including cold temperature, low body mass index (BMI), adrenergic agonists, and elevated concentration of thyroid hormones (3). BAT is found more abundantly in fetuses and infants, with significant regression into adulthood. The main areas where BAT can be found are the neck, mediastinum, axilla, retroperitoneum, and abdominal wall (4). Clinical research suggests that activation and thermogenesis in BAT are mediated by noradrenaline release from the sympathetic nervous system (5). With the increasing use of fluorodeoxyglucose positron emission tomography (18FDG-PET) imaging, there has been an increased detection rate of activated brown adipose tissue (aBAT); this may affect diagnoses and lead to false-positive reporting (6). Phaeochromocytomas/paragangliomas (PPGLs) are chromaffin-cell-derived endocrine tumors that emerge from the adrenal medulla or extra-adrenal ganglia. High FDG accumulation has been commonly noted in aBAT in patients with catecholamine-producing tumours, with subsequent resolution of these findings after resection of the tumour (7). This finding is likely related to the increased glucose transport related to noradrenaline excess (4). BAT has traditionally been considered to mainly express β3-adrenoreceptors; however, in vitro studies have indicated that activated β2-adrenoreceptors may be the main driving force behind thermogenesis (8). Studies reviewing PPGLs have shown an aBAT detection rate of 7.8% to 42.8% on FDG-PET imaging, correlating with elevated catecholamine levels but without clear correlation to germline mutations (9-12). In one study, this imaging finding was associated with a statistically significant reduction in overall survival (12). Standardisation for the 'standardised uptake value' (SUV) cut-offs for aBAT on FDG-PET are lacking, but these are often reported between 1.0 and 2.0 (13); in previous studies of PPGL, a cut-off value of >1.5 has been employed (10, 12). Research on the clinical implications of aBAT in patients with PPGL remains scarce. The main objectives of this study were to gain further insights into BAT activation rates in patients with PPGLs and how this may relate to patient demographics, biochemistry, radiological features, mutational status, and outcomes. The main hypotheses were that aBAT rates would be significantly linked to the severity of catecholamine excess and could be considered a poor prognostic feature.


Description:

References: 1. Santhanam P, Solnes L, Hannukainen JC, Taïeb D. Adiposity-related cancer and functional imaging of brown adipose tissue. Endocr Pract. 2015;21(11):1282-90. 2. Fenzl A, Kiefer FW. Brown adipose tissue and thermogenesis. Horm Mol Biol Clin Investig. 2014;19(1):25-37. 3. Marlatt KL, Ravussin E. Brown adipose tissue: An update on recent findings. Curr Obes Rep. 2017;6(4):389-96. 4. Iyer RB, Guo CC, Perrier N. Adrenal pheochromocytoma with surrounding brown fat stimulation. AJR Am J Roentgenol. 2009;192(1):300-1. 5. Bartness TJ, Vaughan CH, Song CK. Sympathetic and sensory innervation of brown adipose tissue. Int J Obes (Lond). 2010;34 Suppl 1(S1):S36-42. 6. Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007;293(2):E444-52. 7. Terada E, Ashida K, Ohe K, Sakamoto S, Hasuzawa N, Nomura M. Brown adipose activation and reversible beige coloration in adipose tissue with multiple accumulations of 18F-fluorodeoxyglucose in sporadic paraganglioma: A case report. Clin Case Rep. 2019;7(7):1399-403. 8. Blondin DP, Nielsen S, Kuipers EN, Severinsen MC, Jensen VH, Miard S, et al. Human brown adipocyte thermogenesis is driven by β2-AR stimulation. Cell Metab. 2020;32(2):287-300.e7. 9. Wang Q, Zhang M, Ning G, Gu W, Su T, Xu M, et al. Brown adipose tissue in humans is activated by elevated plasma catecholamines levels and is inversely related to central obesity. PLoS One. 2011;6(6):e21006. 10. Puar T, van Berkel A, Gotthardt M, Havekes B, Hermus ARMM, Lenders JWM, et al. Genotype-dependent brown adipose tissue activation in patients with pheochromocytoma and paraganglioma. J Clin Endocrinol Metab. 2016;101(1):224-32. 11. Hadi M, Chen CC, Whatley M, Pacak K, Carrasquillo JA. Brown fat imaging with (18)F-6-fluorodopamine PET/CT, (18)F-FDG PET/CT, and (123)I-MIBG SPECT: a study of patients being evaluated for pheochromocytoma. J Nucl Med. 2007;48(7):1077-83. 12. Abdul Sater Z, Jha A, Hamimi A, Mandl A, Hartley IR, Gubbi S, et al. Pheochromocytoma and paraganglioma patients with poor survival often show brown adipose tissue activation. J Clin Endocrinol Metab. 2020;105(4):1176-85. 13. Sampath SC, Sampath SC, Bredella MA, Cypess AM, Torriani M. Imaging of brown adipose tissue: State of the art. Radiology. 2016;280(1):4-19.


Recruitment information / eligibility

Status Recruiting
Enrollment 100
Est. completion date December 31, 2024
Est. primary completion date September 30, 2024
Accepts healthy volunteers
Gender All
Age group 18 Years to 80 Years
Eligibility Inclusion Criteria: - Patients with confirmed pheochromocytoma or paraganglioma who have undergone a FDG-PET as part of staging process. Exclusion Criteria: - Patients with any other neoplasm other than pheochromocytoma or paraganglioma

Study Design


Related Conditions & MeSH terms


Intervention

Diagnostic Test:
FDG-PET Scan
Positive for activated brown adipose tissue (SUVmax >1.5) FDG-PET scan

Locations

Country Name City State
United Kingdom King's College Hospital NHS Foundation Trust London United Kingdom Of Great Britain And Northern Ireland

Sponsors (1)

Lead Sponsor Collaborator
King's College Hospital NHS Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (13)

Abdul Sater Z, Jha A, Hamimi A, Mandl A, Hartley IR, Gubbi S, Patel M, Gonzales M, Taieb D, Civelek AC, Gharib AM, Auh S, O'Mara AE, Pacak K, Cypess AM. Pheochromocytoma and Paraganglioma Patients With Poor Survival Often Show Brown Adipose Tissue Activation. J Clin Endocrinol Metab. 2020 Apr 1;105(4):1176-85. doi: 10.1210/clinem/dgz314. — View Citation

Bartness TJ, Vaughan CH, Song CK. Sympathetic and sensory innervation of brown adipose tissue. Int J Obes (Lond). 2010 Oct;34 Suppl 1(0 1):S36-42. doi: 10.1038/ijo.2010.182. — View Citation

Blondin DP, Nielsen S, Kuipers EN, Severinsen MC, Jensen VH, Miard S, Jespersen NZ, Kooijman S, Boon MR, Fortin M, Phoenix S, Frisch F, Guerin B, Turcotte EE, Haman F, Richard D, Picard F, Rensen PCN, Scheele C, Carpentier AC. Human Brown Adipocyte Thermogenesis Is Driven by beta2-AR Stimulation. Cell Metab. 2020 Aug 4;32(2):287-300.e7. doi: 10.1016/j.cmet.2020.07.005. — View Citation

Fenzl A, Kiefer FW. Brown adipose tissue and thermogenesis. Horm Mol Biol Clin Investig. 2014 Jul;19(1):25-37. doi: 10.1515/hmbci-2014-0022. — View Citation

Hadi M, Chen CC, Whatley M, Pacak K, Carrasquillo JA. Brown fat imaging with (18)F-6-fluorodopamine PET/CT, (18)F-FDG PET/CT, and (123)I-MIBG SPECT: a study of patients being evaluated for pheochromocytoma. J Nucl Med. 2007 Jul;48(7):1077-83. doi: 10.2967/jnumed.106.035915. Epub 2007 Jun 15. — View Citation

Iyer RB, Guo CC, Perrier N. Adrenal pheochromocytoma with surrounding brown fat stimulation. AJR Am J Roentgenol. 2009 Jan;192(1):300-1. doi: 10.2214/AJR.08.1166. No abstract available. — View Citation

Marlatt KL, Ravussin E. Brown Adipose Tissue: an Update on Recent Findings. Curr Obes Rep. 2017 Dec;6(4):389-396. doi: 10.1007/s13679-017-0283-6. — View Citation

Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007 Aug;293(2):E444-52. doi: 10.1152/ajpendo.00691.2006. Epub 2007 May 1. — View Citation

Puar T, van Berkel A, Gotthardt M, Havekes B, Hermus AR, Lenders JW, van Marken Lichtenbelt WD, Xu Y, Brans B, Timmers HJ. Genotype-Dependent Brown Adipose Tissue Activation in Patients With Pheochromocytoma and Paraganglioma. J Clin Endocrinol Metab. 2016 Jan;101(1):224-32. doi: 10.1210/jc.2015-3205. Epub 2015 Nov 17. — View Citation

Sampath SC, Sampath SC, Bredella MA, Cypess AM, Torriani M. Imaging of Brown Adipose Tissue: State of the Art. Radiology. 2016 Jul;280(1):4-19. doi: 10.1148/radiol.2016150390. — View Citation

Santhanam P, Solnes L, Hannukainen JC, Taieb D. ADIPOSITY-RELATED CANCER AND FUNCTIONAL IMAGING OF BROWN ADIPOSE TISSUE. Endocr Pract. 2015 Nov;21(11):1282-90. doi: 10.4158/EP15870.RA. Epub 2015 Aug 17. — View Citation

Terada E, Ashida K, Ohe K, Sakamoto S, Hasuzawa N, Nomura M. Brown adipose activation and reversible beige coloration in adipose tissue with multiple accumulations of 18F-fluorodeoxyglucose in sporadic paraganglioma: A case report. Clin Case Rep. 2019 Jun 11;7(7):1399-1403. doi: 10.1002/ccr3.2259. eCollection 2019 Jul. — View Citation

Wang Q, Zhang M, Ning G, Gu W, Su T, Xu M, Li B, Wang W. Brown adipose tissue in humans is activated by elevated plasma catecholamines levels and is inversely related to central obesity. PLoS One. 2011;6(6):e21006. doi: 10.1371/journal.pone.0021006. Epub 2011 Jun 20. — View Citation

* Note: There are 13 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Number of patients with pheochromocytoma and metabolically active brown adipose tissue on FGD-PET scan through study completion, an average of 1 year
Primary Number of patients with paraganglioma and metabolically active brown adipose tissue on FGD-PET scan through study completion, an average of 1 year
Secondary Metabolically active brown adipose tissue and presence of germ-line mutations (NHL) in patients with pheochromocytoma and paraganglioma We are going to assess if patients with metabolically active adipose tissue and pheochromocytoma or paraganglioma present with germ-line mutations (VHL) or whether this occurs in patients with sporadic tumours through study completion, an average of 1 year
Secondary Metabolically active brown adipose tissue and presence of germ-line mutations (NF-1) in patients with pheochromocytoma and paraganglioma We are going to assess if patients with metabolically active adipose tissue and pheochromocytoma or paraganglioma present with germ-line mutations (NF-1) or whether this occurs in patients with sporadic tumours through study completion, an average of 1 year
Secondary Metabolically active brown adipose tissue and presence of germ-line mutations (MEN) in patients with pheochromocytoma and paraganglioma We are going to assess if patients with metabolically active adipose tissue and pheochromocytoma or paraganglioma present with germ-line mutations (MEN) or whether this occurs in patients with sporadic tumours through study completion, an average of 1 year
See also
  Status Clinical Trial Phase
Recruiting NCT06050057 - Surgical Treatment of Adrenal Diseases- Laparoscopic vs. Robotic-assisted Adrenalectomy
Recruiting NCT05636618 - Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors Phase 1/Phase 2
Terminated NCT03986593 - Cryoablation of Bone Metastases From Endocrine Tumors N/A
Terminated NCT05948137 - F-18 FDOPA PET/CT Versus I-123 MIBG Scintigraphy With SPECT/CT for the Diagnosis of Pheochromocytoma and Paraganglioma
Completed NCT00970970 - Visualizing Vascular Endothelial Growth Factor (VEGF) Producing Lesions in Von Hippel-Lindau Disease
Active, not recruiting NCT00436735 - Nelfinavir in Treating Patients With Metastatic, Refractory, or Recurrent Solid Tumors Phase 1
Recruiting NCT00669266 - Adrenal Tumors - Pathogenesis and Therapy
Recruiting NCT05069220 - 18F-MFBG PET/CT in the Evaluation of Neural Crest Tumor Early Phase 1
Recruiting NCT06062082 - Intraoperative Hemodynamic Instability During Unilateral Adrenalectomy for Pheochromocytoma
Recruiting NCT04573816 - Development of a Tele-monitoring Program for Patients Undergoing Surgery for Pheochromocytoma and / or Paraganglioma
Active, not recruiting NCT04400474 - Trial of Cabozantinib Plus Atezolizumab in Advanced and Progressive Neoplasms of the Endocrine System. The CABATEN Study Phase 2
Not yet recruiting NCT06045260 - "Receptor Radionuclide Therapy With 177Lu-DOTATOC Phase 2
Completed NCT00001147 - Blood Sampling for Neurochemical and Genetic Testing N/A
Terminated NCT00002947 - Indium In 111 Pentetreotide in Treating Patients With Refractory Cancer Phase 1
Completed NCT00001229 - Diagnosis and Treatment of Pheochromocytoma N/A
Completed NCT01967576 - Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Metastatic, Recurrent or Primary Unresectable Pheochromocytoma/Paraganglioma Phase 2
Recruiting NCT03160274 - Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
Recruiting NCT03206060 - Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/ Paraganglioma Phase 2
Not yet recruiting NCT04788927 - Development of a Predictive Model for the Risk of Metastatic Disease in PPGLs, a Retrospective Cohort Study
Enrolling by invitation NCT03474237 - A Prospective Cohort Study for Patients With Adrenal Diseases