Brown Adipose Tissue Activity and Energy Metabolism in Cachexia (BAT-Cachexia)

Brown Adipose Tissue Activity and Energy Metabolism in Cachexia Induced by Cancer or Chronic Disease

To study BAT activity and energy metabolism in patients with cachexia induced by cancer or chronic disease.

Study Overview

• Status: Completed
• Conditions: Neoplasms; Pulmonary Disease, Chronic Obstructive; Pancreatic Neoplasms; Cachexia
• Intervention / Treatment: Radiation: 18F-FDG PET-MRI-imaging; Radiation: DXA scanning; Procedure: Abdominal subcutaneous adipose tissue biopsy; Procedure: Blood sampling; Other: Indirect calorimetry; Device: Accelerometry; Other: Double-labeled water

Detailed Description

This is a prospective, cross-sectional study to determine BAT activity in cachectic patients with pancreatic or non-small cell lung cancer, and in cachectic patients with chronic obstructive pulmonary disease (COPD), and compare results with healthy individuals and non-cachectic COPD patients, matched for age and BMI.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • Maastricht UMC+

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pancreatic cancer patients, or NSCLC cancer patients, or COPD patients
• The diagnostic criterion for cachexia is unintentional weight loss more than 5% over the past 6 months or more than 2% in individuals with a body-mass index < 20 kg/m2 and muscle wasting assessed by DXA;
• Age ≥ 30 years;
• Gender: male and female;
• Caucasians.

Exclusion Criteria:

• Uncontrolled Diabetes Mellitus;
• Patients with severe clotting disorder;
• Patients with an active second malignancy;
• Psychological unstable persons presumed unfit to perform the measurements, including claustrophobia;
• Persons unable to lie or sit still for 1-2 hours;
• Oxygen therapy;
• Pregnant subjects;Subjects unable to undergo MRI (e.g. pacemaker; neurostimulator; implantable cardioverter-defibrillator (ICD) or leads; Foley bladder catheter; medication pump; cochlear or hearing implant; tattoos or other items that cannot be removed and include metal parts (for instance from operations in the past); metal splinter in the eye; vascular clips; denture, which contains magnets);
• Subjects that received high doses of radiotherapeutic radiation of the neck and/or upper chest in their medical history;
• Persons that received cervical or thoracic sympathectomy or have a nerve dysfunction which is likely to influence sympathetic nerves;
• The use of medication that influences the sympathetic nerve system: ß-blockers, α-blockers, central anti-hypertensives, certain anti-depression drugs (MAO inhibitors, tricyclic anti-depressives), reserpine, cocaine, calciumblockers, labetalol, and certain tranquillizers (fenothiazines).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cachectic pancreatic cancer; Cachectic patients with pancreatic cancer BAT activity: 18F-FDG PET-MRI-imaging. Body composition: DXA scanning, D2O and MRI. Inflammatory and metabolic profile of adipose tissue: abdominal subcutaneous adipose tissue biopsy. Systemic inflammatory profile: blood sampling. Resting metabolic rate: indirect calorimetry. Physical activity level: accelerometry. Total daily energy expenditure: double-labeled water.	Radiation: 18F-FDG PET-MRI-imaging; BAT activity: 18F-FDG PET-MRI-imaging.; Radiation: DXA scanning; Body composition: DXA scanning, D2O and MRI.; Procedure: Abdominal subcutaneous adipose tissue biopsy; Inflammatory and metabolic profile of adipose tissue: abdominal subcutaneous adipose tissue biopsy.; Procedure: Blood sampling; Systemic inflammatory profile: blood sampling.; Other: Indirect calorimetry; Resting metabolic rate: indirect calorimetry.; Device: Accelerometry; Physical activity level: accelerometry.; Other: Double-labeled water; Body composition: DXA scanning, D2O and MRI. Total daily energy expenditure: double-labeled water.
Active Comparator: Cachectic NSCLC; Cachectic patients with non-small cell lung cancer BAT activity: 18F-FDG PET-MRI-imaging. Body composition: DXA scanning, D2O and MRI. Inflammatory and metabolic profile of adipose tissue: abdominal subcutaneous adipose tissue biopsy. Systemic inflammatory profile: blood sampling. Resting metabolic rate: indirect calorimetry. Physical activity level: accelerometry. Total daily energy expenditure: double-labeled water.	Radiation: 18F-FDG PET-MRI-imaging; BAT activity: 18F-FDG PET-MRI-imaging.; Radiation: DXA scanning; Body composition: DXA scanning, D2O and MRI.; Procedure: Abdominal subcutaneous adipose tissue biopsy; Inflammatory and metabolic profile of adipose tissue: abdominal subcutaneous adipose tissue biopsy.; Procedure: Blood sampling; Systemic inflammatory profile: blood sampling.; Other: Indirect calorimetry; Resting metabolic rate: indirect calorimetry.; Device: Accelerometry; Physical activity level: accelerometry.; Other: Double-labeled water; Body composition: DXA scanning, D2O and MRI. Total daily energy expenditure: double-labeled water.
Active Comparator: Cachectic COPD; Cachectic COPD patients. BAT activity: 18F-FDG PET-MRI-imaging. Body composition: DXA scanning, D2O and MRI. Inflammatory and metabolic profile of adipose tissue: abdominal subcutaneous adipose tissue biopsy. Systemic inflammatory profile: blood sampling. Resting metabolic rate: indirect calorimetry. Physical activity level: accelerometry. Total daily energy expenditure: double-labeled water.	Radiation: 18F-FDG PET-MRI-imaging; BAT activity: 18F-FDG PET-MRI-imaging.; Radiation: DXA scanning; Body composition: DXA scanning, D2O and MRI.; Procedure: Abdominal subcutaneous adipose tissue biopsy; Inflammatory and metabolic profile of adipose tissue: abdominal subcutaneous adipose tissue biopsy.; Procedure: Blood sampling; Systemic inflammatory profile: blood sampling.; Other: Indirect calorimetry; Resting metabolic rate: indirect calorimetry.; Device: Accelerometry; Physical activity level: accelerometry.; Other: Double-labeled water; Body composition: DXA scanning, D2O and MRI. Total daily energy expenditure: double-labeled water.
Active Comparator: Non-cachectic COPD; Non-cachectic COPD patients. BAT activity: 18F-FDG PET-MRI-imaging. Body composition: DXA scanning, D2O and MRI. Inflammatory and metabolic profile of adipose tissue: abdominal subcutaneous adipose tissue biopsy. Systemic inflammatory profile: blood sampling. Resting metabolic rate: indirect calorimetry. Physical activity level: accelerometry. Total daily energy expenditure: double-labeled water.	Radiation: 18F-FDG PET-MRI-imaging; BAT activity: 18F-FDG PET-MRI-imaging.; Radiation: DXA scanning; Body composition: DXA scanning, D2O and MRI.; Procedure: Abdominal subcutaneous adipose tissue biopsy; Inflammatory and metabolic profile of adipose tissue: abdominal subcutaneous adipose tissue biopsy.; Procedure: Blood sampling; Systemic inflammatory profile: blood sampling.; Other: Indirect calorimetry; Resting metabolic rate: indirect calorimetry.; Device: Accelerometry; Physical activity level: accelerometry.; Other: Double-labeled water; Body composition: DXA scanning, D2O and MRI. Total daily energy expenditure: double-labeled water.
Other: Healthy individuals; BAT activity: 18F-FDG PET-MRI-imaging. Body composition: DXA scanning, D2O and MRI. Inflammatory and metabolic profile of adipose tissue: abdominal subcutaneous adipose tissue biopsy. Systemic inflammatory profile: blood sampling. Resting metabolic rate: indirect calorimetry. Physical activity level: accelerometry. Total daily energy expenditure: double-labeled water.	Radiation: 18F-FDG PET-MRI-imaging; BAT activity: 18F-FDG PET-MRI-imaging.; Radiation: DXA scanning; Body composition: DXA scanning, D2O and MRI.; Procedure: Abdominal subcutaneous adipose tissue biopsy; Inflammatory and metabolic profile of adipose tissue: abdominal subcutaneous adipose tissue biopsy.; Procedure: Blood sampling; Systemic inflammatory profile: blood sampling.; Other: Indirect calorimetry; Resting metabolic rate: indirect calorimetry.; Device: Accelerometry; Physical activity level: accelerometry.; Other: Double-labeled water; Body composition: DXA scanning, D2O and MRI. Total daily energy expenditure: double-labeled water.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brown adipose tissue (BAT) activity measured by PET(-MRI)	The main endpoint of this study is BAT volume and intensity of activity in Standard Uptake Value (SUV) in the presence of cancer cachexia, COPD cachexia, and compared to non-cachectic COPD patients and healthy individuals, as assessed by 18F-fluoro-deoxyglucose (18F-FDG) PET-MRI scanning.	participants will be followed for 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total energy metabolism measured by resting energy expenditure (REE) and doubly labeled water		participants will be followed for 2 weeks
Resting metabolic rate measured by REE		participants will be followed for 2 weeks
Metabolic gene expression in WAT measured by biopsy of subcutaneous fat		participants will be followed for 2 weeks
Systemic inflammatory status measured in blood		participants will be followed for 2 weeks
Fat tissue mass measured by MRI, DXA, and doubly labeled water	Detailed body composition phenotyping of cachexia by (PET-)MRI to compare with commonly applied clinical measures (D2O and DXA)	participants will be followed for 2 weeks
Hormonal status measured in blood		participants will be followed for 2 weeks
Lean tissue mass measured by MRI, DXA, and doubly labeled water	Detailed body composition phenotyping of cachexia by (PET-)MRI to compare with commonly applied clinical measures (D2O and DXA)	participants will be followed for 2 weeks

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Annemie Schols, PhD, Maastricht UMC

Publications and helpful links

General Publications

• Sanders K, Klooster K, Vanfleteren LEGW, Plasqui G, Dingemans AM, Slebos DJ, Schols AMWJ. Effect of Bronchoscopic Lung Volume Reduction in Advanced Emphysema on Energy Balance Regulation. Respiration. 2021 Feb 5:1-8. doi: 10.1159/000511920. [Epub ahead of print]

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): July 1, 2018

Study Registration Dates

• First Submitted: June 24, 2015
• First Submitted That Met QC Criteria: July 14, 2015
• First Posted (Estimate): July 16, 2015

Study Record Updates

• Last Update Posted (Actual): August 3, 2018
• Last Update Submitted That Met QC Criteria: August 1, 2018
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Respiratory Tract Diseases; Lung Diseases; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Nutrition Disorders; Body Weight; Lung Diseases, Obstructive; Body Weight Changes; Pancreatic Diseases; Emaciation; Weight Loss; Neoplasms; Pulmonary Disease, Chronic Obstructive; Pancreatic Neoplasms; Wasting Syndrome; Cachexia; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: 142071; NL51402.068.14 (Other Identifier: CCMO)