Ignite Creation Date:
2024-06-16 @ 11:51 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06440122
Status:
RECRUITING
Last Update Posted:
2024-06-03
First Post:
2024-05-21
Brief Title:
The Incidence and Outcomes of Metabolically Active Brown Adipose Tissue aBAT in Patients With Pheochromocytoma or Paraganglioma PPGLs
Sponsor:
Kings College Hospital NHS Trust
Organization:
Kings College Hospital NHS Trust
Study Overview
Official Title:
The Incidence and Outcomes of Metabolically Active Brown Adipose Tissue aBAT in Patients With Pheochromocytoma or Paraganglioma PPGLs
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
Phaeochromocytomasparagangliomas 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 78 to 428 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 10 and 20 13 in previous studies of PPGL a cut-off value of 15 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
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
Phaeochromocytomasparagangliomas 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 78 to 428 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 10 and 20 13 in previous studies of PPGL a cut-off value of 15 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
Detailed Description:
References
1 Santhanam P Solnes L Hannukainen JC Taïeb D Adiposity-related cancer and functional imaging of brown adipose tissue Endocr Pract 201521111282-90
2 Fenzl A Kiefer FW Brown adipose tissue and thermogenesis Horm Mol Biol Clin Investig 201419125-37
3 Marlatt KL Ravussin E Brown adipose tissue An update on recent findings Curr Obes Rep 201764389-96
4 Iyer RB Guo CC Perrier N Adrenal pheochromocytoma with surrounding brown fat stimulation AJR Am J Roentgenol 20091921300-1
5 Bartness TJ Vaughan CH Song CK Sympathetic and sensory innervation of brown adipose tissue Int J Obes Lond 201034 Suppl 1S1S36-42
6 Nedergaard J Bengtsson T Cannon B Unexpected evidence for active brown adipose tissue in adult humans Am J Physiol Endocrinol Metab 20072932E444-52
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 2019771399-403
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 2020322287-300e7
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 201166e21006
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 20161011224-32
11 Hadi M Chen CC Whatley M Pacak K Carrasquillo JA Brown fat imaging with 18F-6-fluorodopamine PETCT 18F-FDG PETCT and 123I-MIBG SPECT a study of patients being evaluated for pheochromocytoma J Nucl Med 20074871077-83
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 202010541176-85
13 Sampath SC Sampath SC Bredella MA Cypess AM Torriani M Imaging of brown adipose tissue State of the art Radiology 201628014-19
1 Santhanam P Solnes L Hannukainen JC Taïeb D Adiposity-related cancer and functional imaging of brown adipose tissue Endocr Pract 201521111282-90
2 Fenzl A Kiefer FW Brown adipose tissue and thermogenesis Horm Mol Biol Clin Investig 201419125-37
3 Marlatt KL Ravussin E Brown adipose tissue An update on recent findings Curr Obes Rep 201764389-96
4 Iyer RB Guo CC Perrier N Adrenal pheochromocytoma with surrounding brown fat stimulation AJR Am J Roentgenol 20091921300-1
5 Bartness TJ Vaughan CH Song CK Sympathetic and sensory innervation of brown adipose tissue Int J Obes Lond 201034 Suppl 1S1S36-42
6 Nedergaard J Bengtsson T Cannon B Unexpected evidence for active brown adipose tissue in adult humans Am J Physiol Endocrinol Metab 20072932E444-52
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 2019771399-403
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 2020322287-300e7
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 201166e21006
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 20161011224-32
11 Hadi M Chen CC Whatley M Pacak K Carrasquillo JA Brown fat imaging with 18F-6-fluorodopamine PETCT 18F-FDG PETCT and 123I-MIBG SPECT a study of patients being evaluated for pheochromocytoma J Nucl Med 20074871077-83
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 202010541176-85
13 Sampath SC Sampath SC Bredella MA Cypess AM Torriani M Imaging of brown adipose tissue State of the art Radiology 201628014-19
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None