Short Chain Fatty Acid Metabolism in COPD

NCT ID: NCT03327181

Last Updated: 2025-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-19
• Study Completion Date: 2019-02-14

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.

Conditions

Chronic Obstructive Pulmonary Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

COPD

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.

Group Type: EXPERIMENTAL

short chain fatty acid tracers

Intervention Type: DIETARY_SUPPLEMENT

stable tracer infusion of acetate, propionate, and butyrate

Healthy older adults

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.

Group Type: ACTIVE_COMPARATOR

short chain fatty acid tracers

Intervention Type: DIETARY_SUPPLEMENT

stable tracer infusion of acetate, propionate, and butyrate

Interventions

short chain fatty acid tracers

stable tracer infusion of acetate, propionate, and butyrate

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• 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

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Texas A&M University

OTHER

Sponsor Role: lead

Responsible Party

Marielle PKJ Engelen, PhD

PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marielle Engelen, PhD

Role: PRINCIPAL_INVESTIGATOR

Texas A&M University

Locations

Texas A&M University

College Station, Texas, United States

Countries

United States

References

Engelen MPKJ, Kirschner SK, Coyle KS, Argyelan D, Neal G, Dasarathy S, Deutz NEP. Sex related differences in muscle health and metabolism in chronic obstructive pulmonary disease. Clin Nutr. 2023 Sep;42(9):1737-1746. doi: 10.1016/j.clnu.2023.06.031. Epub 2023 Jul 26.

Reference Type: DERIVED

PMID: 37542951 (View on PubMed)

Other Identifiers

2017-0112

Identifier Type: -

Identifier Source: org_study_id