Eicosapentaenoic Acid and Protein Modulation to Induce Anabolism in Chronic Obstructive Pulmonary Disease (COPD): Aim 2

NCT01624792 | Completed

• 1 other identifier: 2012-0171
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

Loss of muscle protein is generally a central component of weight loss in Chronic Obstructive Pulmonary Disease (COPD) patients. Gains in muscle mass are difficult to achieve in COPD unless specific metabolic abnormalities are targeted. The investigators recently observed that alterations in protein metabolism are present in normal weight COPD patients. Elevated levels of protein synthesis and breakdown rates were found in this COPD group indicating that alterations are already present before muscle wasting occurs. The investigators recently observed that in order to enhance protein anabolism, manipulation of the composition of proteins and amino acids in nutrition is required in normal-weight COPD. Intake of casein protein resulted into significant protein anabolism in these patients. The anabolic response to casein protein was even higher than after whey protein intake. A substantial number of COPD patients, underweight as well as normal weight to obese, is characterized by an increased inflammatory response. This group failed to respond to nutritional therapy. Previous experimental research and clinical studies in cachectic conditions (mostly malignancy) indicate that polyunsaturated fatty acids (PUFA) are able to attenuate protein degradation by improving the anabolic response to feeding and by decreasing the acute phase response. Eicosapentaenoic acid (EPA) (in combination with docosahexaenoic acid (DHA)) has been shown to effectively inhibit weight loss in several disease states, however weight and muscle mass gain was not present or minimal. Until now, limited research has been done examining muscle protein metabolism and the response to EPA and DHA supplementation in patients with COPD. It is the investigator's hypothesis that supplementation of 2g/day EPA+DHA in COPD patients during 4 consecutive weeks will increase the muscle anabolic response to a high quality protein supplement as compared to a placebo, and supplementation of 3.5g/day EPA+DHA will increase the anabolic response even further. In the present study both the acute and chronic effects of EPA+DHA versus a placebo on muscle and whole body protein metabolism will be examined. The principal endpoint will be the extent of stimulation of net fractional muscle protein synthesis as this is the principal mechanism by which the effect of EPA+DHA on muscle anabolism can be measured. The endpoint will be assessed by isotope methodology which is thought to be the reference method.

Conditions

Chronic Obstructive Pulmonary Disease; Muscle Wasting

Keywords

Protein metabolism; casein protein; EPA; Fish oil

Outcome Measures

Primary Outcomes (1)

• Fractional muscle protein synthesis and breakdown rate (FSR and FBR) of mixed muscle protein (%/h) and net fractional muscle protein synthesis (nFSR = FSR - FBR)

  On the study days the primary outcome measure is determined acutely before and after 4 hours of feeding and after intake of either the 3.5 g EPA+DHA, a placebo or 2.0 g EPA+DHA (last category only applicable to COPD group). After study day 1 COPD patients undergo a 4-week intervention period of daily EPA+DHA or placebo supplementation and on their return visit (2nd study day) the primary outcome measure is determined again.

  Acutely before and after 4 hours of feeding and the change after 4 weeks of EPA+DHA or placebo supplementation

Secondary Outcomes (9)

• Net whole body protein synthesis (whole body protein synthesis and breakdown rate)

  Acutely before and after 4 hours of feeding and the change after 4 weeks of EPA+DHA or placebo supplementation

• Whole body myofibrillar protein breakdown rate

  Acutely before and after 4 hours of feeding and the change after 4 weeks of EPA+DHA or placebo supplementation

• Glutathione turnover

  Acutely before and after 4 hours of feeding and the change after 4 weeks of EPA+DHA or placebo supplementation

• Body composition

  On study day 1 and the change from study day 1 on study day 2

• Skeletal and respiratory muscle strength and fatigue

  On study day 1 and the change from study day 1 on study day 2

Study Arms (2)

Healthy older adults

EXPERIMENTAL

Healthy controls will receive each intervention (olive oil or fish oil with 3.5 g EPA+DHA) one time and for only one day per intervention .

Dietary Supplement: Olive oil; Dietary Supplement: Fish oil

COPD patients

EXPERIMENTAL

COPD patients will receive one out of three possible interventions (olive oil or fish oil with 3.5 g EPA+DHA or fish oil and placebo with 2 g EPA+DHA) for 4 (+/- 7 days) weeks.

Dietary Supplement: Olive oil; Dietary Supplement: Fish oil; Dietary Supplement: Fish oil and placebo

Interventions

Olive oil DIETARY_SUPPLEMENT

Dose: 7.0 g/day (= 7 capsules/day).

COPD patients; Healthy older adults

Fish oil DIETARY_SUPPLEMENT

Dose: 7.0 g/day (= 7 capsules/day = 3.5g EPA+DHA/day).

COPD patients; Healthy older adults

Fish oil and placebo DIETARY_SUPPLEMENT

Dose: 7.0 g/day (= 4 capsules/day fish oil = 2.0g EPA+DHA/day and 3 capsules/day olive oil).

COPD patients

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to walk, sit down and stand up independently
• Age 45 years or older
• Ability to lay in supine or elevated position for 8 hours
• Diagnosis of moderate to severe chronic airflow limitation, defined as measured forced expiratory volume in one second (FEV1) ≤ 70% of referen¬ce FEV1
• Clinically stable condition and not suffering from 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 study
• Shortness of breath on exertion
• Willingness and ability to comply with the protocol, including:
• Refraining from alcohol consumption (24 h) and intense physical activities (72h) prior to each study visit
• Adhering to fasting state from 10 pm ± 2h onwards the day prior to each study visit
• 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 or older
• Ability to lay in supine or elevated position for 8 hours
• No diagnosis of COPD and forced expiratory volume in one second (FEV1) \> 80% of referen¬ce FEV1
• Willingness and ability to comply with the protocol, including:

You may not qualify if:

• Any condition that may interfere with the definition 'healthy subject' according to the investigator's judgment (for healthy control group only)
• Established diagnosis of malignancy
• Established diagnosis of Diabetes Mellitus
• History of untreated metabolic diseases including hepatic or renal disorder
• Presence of acute illness or metabolically unstable chronic illness
• Recent myocardial infarction (less than 1 year)
• Any other condition according to the PI or study physicians would interfere with proper conduct of the study / safety of the patient
• BMI ≥ 40 kg/m2
• Dietary or lifestyle characteristics:
• Use of supplements containing EPA+DHA 3 months prior to the first test day Use of protein or amino acid containing nutritional supplements within 5 days of first study day
• Current alcohol or drug abuse
• Indications related to interaction with study products:
• Known allergy to milk or milk products
• Known hypersensitivity to fish and/or shellfish, Swanson EFAs Super EPA Fish oil or any of its ingredients, Swanson EFAs Certified Organic Extra Virgin Olive oil or any of its ingredients
• Contraindications to biopsy procedure:

Sponsors & Collaborators

• Texas A&M University: lead

Study Sites (1)

Texas A&M University

College Station, Texas, 77843, United States

Location

Related Publications (2)

• 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.

  PMID: 37542951 DERIVED

• Engelen MPKJ, Jonker R, Sulaiman H, Fisk HL, Calder PC, Deutz NEP. omega-3 polyunsaturated fatty acid supplementation improves postabsorptive and prandial protein metabolism in patients with chronic obstructive pulmonary disease: a randomized clinical trial. Am J Clin Nutr. 2022 Sep 2;116(3):686-698. doi: 10.1093/ajcn/nqac138.

  PMID: 35849009 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Muscular Atrophy

Interventions

Olive Oil; Fish Oils

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fats, Unsaturated; Plant Oils; Oils; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Marielle Engelen, PhD

  Texas A&M University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: June 5, 2012
• First Posted: June 21, 2012
• Study Start: October 25, 2011
• Primary Completion: June 29, 2016
• Study Completion: June 29, 2016
• Last Updated: September 30, 2025

Record last verified: 2025-09

Locations

US (1)