To study BAT activity and energy metabolism in patients with cachexia induced by cancer or chronic disease.
ID
Source
Brief title
Condition
- Metabolism disorders NEC
- Gastrointestinal neoplasms malignant and unspecified
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main endpoint of this study is BAT volume and intensity of activity in SUV
in the presence of cancer cachexia, COPD cachexia, and compared to
non-cachectic COPD patients and healthy individuals, as assessed by 18F-FDG
PET-MRI scanning.
Secondary outcome
Secondary endpoints are the relation of BAT activity to a) total energy
metabolism and resting metabolic rate and b) metabolic gene expression in WAT
and c) systemic inflammatory and hormonal status. Furthermore the PET-MRI
allows detailed body composition phenotyping of cachexia to compare with
commonly applied clinical measures (D2O and DEXA). Furthermore, dyspnea or
meal-related oxygen desaturation, 6 minute walking test and heart rithm will be
evaluated.
Background summary
Evidence by rodent studies in tumour models with cachexia have shown an
association between weight loss and thermogenic activation of brown adipose
tissue (BAT), providing evidence for a role of BAT activation in the
progression of (cancer) cachexia. . BAT has not been investigated in relation
to COPD but a recent rodent model of COPD associated cachexia showed elevated
white adipose tissue (WAT) metabolic gene expression and browning of WAT.
Previous autopsy samples have shown that high prevalence of BAT in
cancer-induced cachexia could be related to the hypermetabolic state of these
patients. Recent introduction of 18F-FDG PET-CT led to more awareness of BAT
activity. The observation of BAT in oncology patient staging by 18F-FDG PET-CT
scanning as well as the strong correlation between BAT activity and body mass
index (BMI) has strengthened the notion that BAT activation may contribute to
elevated energy requirements in patients with cachexia. We hypothesize that
BAT volume and activity is increased in cachectic patients induced by either
cancer or COPD, and contributes to elevated energy metabolic rate.
Furthermore, in COPD it is hypothesized that energy expenditure is elevated due
to impaired lung mechanics. The recently introduced lung volume reduction
procedure by endobronchial valves ia an unique model to test the influence of
lung mechanics on energy balance in COPD.
Study objective
To study BAT activity and energy metabolism in patients with cachexia induced
by cancer or chronic disease.
Study design
Cross-sectional study: Determine BAT activity in cachectic patients with
pancreatic or non-small cell lung cancer, and in cachectic COPD patients, and
compare results with healthy individuals and non-cachectic COPD patients,
matched for gender, age and BMI in a prospective cross-sectional design.
Intervention
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.
Study burden and risks
The total absorbed radiation dose from one 18F-FDG PET-scan after
administration of 150 MBq of 18F-FDG is 2.9 mSv, which is considered as a low
risk. The other measurements and procedures have very low risks.
P. Debyelaan 25
Maastricht 6229 HX
NL
P. Debyelaan 25
Maastricht 6229 HX
NL
Listed location countries
Age
Inclusion criteria
Cachectic pancreatic cancer patients:
* Stage I-IV pancreatic cancer 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;
Cachectic NSCLC patients:
* Stage I-IV NSCLC 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;;Cachectic COPD patients:
* COPD GOLD I-IV (COPD patients with and without receiving lung volume reduction by endobronchial valves);
* 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;;Non-cachectic COPD patients:
* COPD GOLD I-IV (COPD patients with and without receiving lung volume reduction by endobronchial valves);
* Age * 30 years;
* Gender: male and female;;Healthy individuals:
* Age * 30 years;
* Gender: male and female;;Emphysematous COPD patients:
* Receiving lung volume reduction by endobronchial valves
* Age * 30 years;
* Gender: male and female;
Exclusion criteria
Cachectic pancreatic cancer patients:
* 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; 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, *-blockers, central anti-hypertensives, certain anti-depression drugs (MAO inhibitors, tricyclic anti-depressives), reserpine, cocaïne, calciumblockers, labetalol, and certain tranquillizers (fenothiazines).;Cachectic NSCLC patients:
* 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; 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, *-blockers, central anti-hypertensives, certain anti-depression drugs (MAO inhibitors, tricyclic anti-depressives), reserpine, cocaïne, calciumblockers, labetalol, and certain tranquillizers (fenothiazines).;Cachectic COPD patients:
* 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; 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, *-blockers, central anti-hypertensives, certain anti-depression drugs (MAO inhibitors, tricyclic anti-depressives), reserpine, cocaïne, calciumblockers, labetalol, and certain tranquillizers (fenothiazines).;Non-cachectic COPD patients:
* 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; 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, *-blockers, central anti-hypertensives, certain anti-depression drugs (MAO inhibitors, tricyclic anti-depressives), reserpine, cocaïne, calciumblockers, labetalol, and certain tranquillizers (fenothiazines).;Healthy individuals:
* Psychological unstable persons presumed unfit to perform the measurements, including claustrophobia;
* Persons unable to lie or sit still for 1-2 hours;
* Pregnant subjects;
* Subjects unable to undergo MRI (e.g. pacemaker; neurostimulator; 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, *-blockers, central anti-hypertensives, certain anti-depression drugs (MAO inhibitors, tricyclic anti-depressives), reserpine, cocaïne, calciumblockers, labetalol, and certain tranquillizers (fenothiazines).;Emphysematous COPD patients:
* Patients with an active malignancy;
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02500004 |
| CCMO | NL51402.068.14 |