Short Chain Fatty Acid Metabolism in COPD
- Conditions
- Chronic Obstructive Pulmonary Disease
- Interventions
- Dietary Supplement: short chain fatty acid tracers
- Registration Number
- NCT03327181
- Lead Sponsor
- Texas A&M University
- Brief Summary
The short chain fatty acid (SCFA) metabolism has not been studied in subjects suffering from COPD. The purpose of this study is to compare the SCFA metabolism in COPD patients to healthy matched controls. This protocol is an extension of recent studies about protein digestion and absorption abnormalities in COPD patients. The investigators hypothesize that SCFA production might be lower in COPD patients than in healthy subjects.
- Detailed Description
Short-chain fatty acids (SCFAs) are straight or branched-chain fatty acids produced by the intestinal microbiota mainly through fermentation of undigested carbohydrates, but also through degradation of dietary and endogenous proteins. With a share of 90 to 95 %, acetate (C2), propionate (C3), and butyrate (C4) are the most common SCFAs in the colon (3). The molar ratios of acetate to propionate to butyrate are on average approximately 60:20:20 throughout the whole colon. Several human studies tried to determine the in situ production of SCFAs by measuring their content in feces (5-8). But fecal SCFA concentrations do not accurately represent the concentrations in more proximal regions of the colon, because colonocytes absorb more than 95 % of SCFAs to use them as an energy source. Further, the measurement of plasma SCFA concentrations is inaccurate because SCFA plasma levels are low due to high metabolism in colonocytes and liver. Thus, stable isotope studies are needed to examine the colonic production and metabolic fate of SCFAs in healthy and diseased subjects.
SCFAs seem to have anti-inflammatory and immune modulating effects. In COPD an enhanced pulmonary inflammatory response causes a combination of small airways disease (e.g., obstructive bronchiolitis) and/or a destruction of lung parenchyma (emphysema). This leads to a progressive and persistent airflow limitation. Smoking and the exposure to polluted air are main risk factors causing COPD. In a mouse model, a diet rich in whey proteins attenuated emphysema through the suppression of respiratory inflammation. This might have been related to a high colonic SCFA concentration due to the diet. Young et al. proposed that in smokers SCFAs might mitigate both the innate-mediated systemic inflammation controlled by the liver and the inflammatory responses in the lung.
Moreover, Nielsen et al. found that gastrointestinal diseases are significantly more prevalent in COPD patients (15 %) than in patients with other diseases (9%). This might have an influence on the SCFA production in the colon. Gastrointestinal problems may also be assessed through the usage of validated questionnaires.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description COPD short chain fatty acid tracers The subject will arrive fasted. A catheter will be inserted in the arm for stable tracer SCFA infusion and blood sampling. The hand of the arm used for blood sampling will be placed in a thermostatically controlled warmed box that heats the air. Immediately after a baseline blood sample is taken, an infusion with stable tracers will be administered by the research nurse. Stable tracers are given to measure SCFA metabolism. Blood samples will be collected before and/or after infusion. Subjects will be asked to complete a list of questions regarding quality of life, mood and depression, diet, and a variety of functional measurements. Healthy older adults short chain fatty acid tracers The subject will arrive fasted. A catheter will be inserted in the arm for stable tracer SCFA infusion and blood sampling. The hand of the arm used for blood sampling will be placed in a thermostatically controlled warmed box that heats the air. Immediately after a baseline blood sample is taken, an infusion with stable tracers will be administered by the research nurse. Stable tracers are given to measure SCFA metabolism. Blood samples will be collected before and/or after infusion. Subjects will be asked to complete a list of questions regarding quality of life, mood and depression, diet, and a variety of functional measurements.
- Primary Outcome Measures
Name Time Method whole body short-chain fatty acid metabolism -10, 2, 4, 6, 8, 10, 15, 20, 25, 30, 40, 50, 60 min change in whole body scfa metabolism
- Secondary Outcome Measures
Name Time Method Fat free mass measured using dual-energy x-ray absorptiometry 1 day Difference in muscle mass between COPD patients and healthy older adults
handgrip strength dynamometry 1 day Difference in handgrip strength between COPD patients and healthy older adults
moving balance platform measurement 1 day Changes in ability to maintain balance after perturbation of moving platform between COPD patients and healthy older adults. The maximum platform displacement the participant could withstand without stepping will be determined.
Bone density measured using dual-energy x-ray absorptiometry 1 day Difference in bone density between COPD patients and healthy older adults
COPD Assessment Test 1 day self-administered questionnaire regarding impact of COPD on daily life
Group differences in attention and executive functions as measured by Trail Making Test (TMT), 1 day In Part A, the examinee is instructed to connect a set of 25 circles with numbers as quickly as possible while maintaining accuracy. In Part B, the examinee is instructed to connect a set of 25 circles, alternating between numbers and letters, as quickly as possible while maintaining accuracy. Measures attentional resources and is a measure of the frontal lobe "executive" functions of visual search, set-switching and mental flexibility. The total time in seconds was reported for each measure.
Group differences in physical activity as reported by "International Physical Activity Questionnaire" 1 day self-administered questionnaire regarding physical activity
Fat mass measured using dual-energy x-ray absorptiometry 1 day Difference in fat mass between COPD patients and healthy older adults
Micro-respiratory pressure meter measurement 1 day Difference in maximum inspiratory and expiratory pressure between COPD patients and healthy older adults
Group differences in somatosensory functions as measured by vibrotactile behavioral battery 1 day The vibrotactile behavioral battery consists of a non-invasive set of brief tasks targeting sensory processes and inhibition. It can be used to detect neurobiological abnormalities in sensory processing. The battery of vibrotactile tasks involves the use of a small device that is designed to administer calibrated vibratory stimuli to the glabrous skin of digits 3 and 4 of the left hand and is connected to a laptop computer.
Group differences in gut function as reported by "The Gastrointestinal Symptom Rating Scale" 1 day self-administered questionnaire regarding gut function and associated symptoms
Group differences in attention and executive functions as measured by Stroop Color-Word Test (SCWT), 1 day a word page with words printed in black ink, a color page with blocks printed in color, and a color-word page where the color and the word do not match. The examinee reads the words or names the ink colors as quickly as possible within a time limit. Measures selective attention and inhibitory control. The total time in seconds was reported for each trial.
Trial Locations
- Locations (1)
Texas A&M University
🇺🇸College Station, Texas, United States