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Short Chain Fatty Acid Metabolism in COPD (SCFA)

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status
Unknown status
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
short chain fatty acid tracers
Sponsored by
Texas A&M University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Chronic Obstructive Pulmonary Disease focused on measuring short chain fatty acid metabolism

Eligibility Criteria

45 Years - 100 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion criteria COPD subjects:

  • Ability to walk, sit down and stand up independently
  • Age 45 years - 100 years
  • Ability to lie in supine or elevated position for 1.5 hours
  • Diagnosis of moderate to very severe chronic airflow limitation and compliant to the following criteria: FEV1 < 70% of reference FEV1
  • Clinically stable condition and not suffering from a respiratory tract infection or exacerbation of their disease (defined as a combination of increased cough, sputum purulence, shortness of breath, systemic symptoms such as fever, and a decrease in FEV1 > 10% compared with values when clinically stable in the preceding year) at least 4 weeks prior to the first test day
  • Shortness of breath on exertion
  • Willingness and ability to comply with the protocol

Inclusion criteria control subjects:

  • Healthy male or female according to the investigator's or appointed staff's judgment
  • Ability to walk, sit down and stand up independently
  • Age 45 years - 100 years
  • Ability to lay in supine or elevated position for 1.5 hours
  • No diagnosis of COPD
  • Willingness and ability to comply with the protocol

Exclusion Criteria all subjects:

  • Any condition that may interfere with the definition 'healthy subject' according to the investigator's judgment (healthy subjects only)
  • Subjects 86 years and older that fail to get physician eligibility confirmation
  • Insulin dependent diabetes mellitus
  • Established diagnosis of malignancy
  • History of untreated metabolic diseases including hepatic or renal disorder
  • Presence of acute illness or metabolically unstable chronic illness
  • Presence of fever within the last 3 days
  • Any other condition according to the PI or nurse that was found during the screening visit, that would interfere with the study or safety of the patient
  • Use of protein or amino acid containing nutritional supplements within 5 days of first study day
  • Use of short course of oral corticosteroids within 4 weeks preceding first study day
  • Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements
  • (Possible) pregnancy
  • Already enrolled in another clinical trial and that clinical trial interferes with participating in this study

When during the period from enrollment to the test day any condition causing the subject to not meet inclusion criteria or to meet exclusion criteria, the subject will be excluded from the study.

Sites / Locations

  • Texas A&M University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

COPD

Healthy older adults

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

whole body short-chain fatty acid metabolism
change in whole body scfa metabolism

Secondary Outcome Measures

Fat free mass measured using dual-energy x-ray absorptiometry
Difference in muscle mass between COPD patients and healthy older adults
Fat mass measured using dual-energy x-ray absorptiometry
Difference in fat mass between COPD patients and healthy older adults
Bone density measured using dual-energy x-ray absorptiometry
Difference in bone density between COPD patients and healthy older adults
handgrip strength dynamometry
Difference in handgrip strength between COPD patients and healthy older adults
Micro-respiratory pressure meter measurement
Difference in maximum inspiratory and expiratory pressure between COPD patients and healthy older adults
moving balance platform measurement
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.
Group differences in attention and executive functions as measured by Trail Making Test (TMT),
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 attention and executive functions as measured by Stroop Color-Word Test (SCWT),
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.
Group differences in somatosensory functions as measured by vibrotactile behavioral battery
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"
self-administered questionnaire regarding gut function and associated symptoms
Group differences in physical activity as reported by "International Physical Activity Questionnaire"
self-administered questionnaire regarding physical activity
COPD Assessment Test
self-administered questionnaire regarding impact of COPD on daily life

Full Information

First Posted
October 10, 2017
Last Updated
June 17, 2020
Sponsor
Texas A&M University
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1. Study Identification

Unique Protocol Identification Number
NCT03327181
Brief Title
Short Chain Fatty Acid Metabolism in COPD
Acronym
SCFA
Official Title
Short-chain Fatty Acid Metabolism in Chronic Obstructive Pulmonary Disease
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Unknown status
Study Start Date
April 19, 2017 (Actual)
Primary Completion Date
April 2021 (Anticipated)
Study Completion Date
April 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Texas A&M University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
Keywords
short chain fatty acid metabolism

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
COPD
Arm Type
Experimental
Arm Description
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.
Arm Title
Healthy older adults
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
short chain fatty acid tracers
Intervention Description
stable tracer infusion of acetate, propionate, and butyrate
Primary Outcome Measure Information:
Title
whole body short-chain fatty acid metabolism
Description
change in whole body scfa metabolism
Time Frame
-10, 2, 4, 6, 8, 10, 15, 20, 25, 30, 40, 50, 60 min
Secondary Outcome Measure Information:
Title
Fat free mass measured using dual-energy x-ray absorptiometry
Description
Difference in muscle mass between COPD patients and healthy older adults
Time Frame
1 day
Title
Fat mass measured using dual-energy x-ray absorptiometry
Description
Difference in fat mass between COPD patients and healthy older adults
Time Frame
1 day
Title
Bone density measured using dual-energy x-ray absorptiometry
Description
Difference in bone density between COPD patients and healthy older adults
Time Frame
1 day
Title
handgrip strength dynamometry
Description
Difference in handgrip strength between COPD patients and healthy older adults
Time Frame
1 day
Title
Micro-respiratory pressure meter measurement
Description
Difference in maximum inspiratory and expiratory pressure between COPD patients and healthy older adults
Time Frame
1 day
Title
moving balance platform measurement
Description
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.
Time Frame
1 day
Title
Group differences in attention and executive functions as measured by Trail Making Test (TMT),
Description
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.
Time Frame
1 day
Title
Group differences in attention and executive functions as measured by Stroop Color-Word Test (SCWT),
Description
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.
Time Frame
1 day
Title
Group differences in somatosensory functions as measured by vibrotactile behavioral battery
Description
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.
Time Frame
1 day
Title
Group differences in gut function as reported by "The Gastrointestinal Symptom Rating Scale"
Description
self-administered questionnaire regarding gut function and associated symptoms
Time Frame
1 day
Title
Group differences in physical activity as reported by "International Physical Activity Questionnaire"
Description
self-administered questionnaire regarding physical activity
Time Frame
1 day
Title
COPD Assessment Test
Description
self-administered questionnaire regarding impact of COPD on daily life
Time Frame
1 day

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria COPD subjects: Ability to walk, sit down and stand up independently Age 45 years - 100 years Ability to lie in supine or elevated position for 1.5 hours Diagnosis of moderate to very severe chronic airflow limitation and compliant to the following criteria: FEV1 < 70% of reference FEV1 Clinically stable condition and not suffering from a respiratory tract infection or exacerbation of their disease (defined as a combination of increased cough, sputum purulence, shortness of breath, systemic symptoms such as fever, and a decrease in FEV1 > 10% compared with values when clinically stable in the preceding year) at least 4 weeks prior to the first test day Shortness of breath on exertion Willingness and ability to comply with the protocol Inclusion criteria control subjects: Healthy male or female according to the investigator's or appointed staff's judgment Ability to walk, sit down and stand up independently Age 45 years - 100 years Ability to lay in supine or elevated position for 1.5 hours No diagnosis of COPD Willingness and ability to comply with the protocol Exclusion Criteria all subjects: Any condition that may interfere with the definition 'healthy subject' according to the investigator's judgment (healthy subjects only) Subjects 86 years and older that fail to get physician eligibility confirmation Insulin dependent diabetes mellitus Established diagnosis of malignancy History of untreated metabolic diseases including hepatic or renal disorder Presence of acute illness or metabolically unstable chronic illness Presence of fever within the last 3 days Any other condition according to the PI or nurse that was found during the screening visit, that would interfere with the study or safety of the patient Use of protein or amino acid containing nutritional supplements within 5 days of first study day Use of short course of oral corticosteroids within 4 weeks preceding first study day Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements (Possible) pregnancy Already enrolled in another clinical trial and that clinical trial interferes with participating in this study When during the period from enrollment to the test day any condition causing the subject to not meet inclusion criteria or to meet exclusion criteria, the subject will be excluded from the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marielle Engelen, PhD
Organizational Affiliation
Texas A&M University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Texas A&M University
City
College Station
State/Province
Texas
ZIP/Postal Code
77843-4253
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Short Chain Fatty Acid Metabolism in COPD

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