Brown Adipose Tissue Activity and Energy Metabolism in Cachexia

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

Detailed Description
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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.

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

Conditions
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Cachexia, Neoplasms, Pulmonary Disease, Chronic Obstructive, Pancreatic Neoplasms

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |