- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03796455
Fish Oil and HMB Supplementation in COPD (COPD fish oil)
Effects of Low Dose of Fish Oil (EPA+DHA) vs. Combined EPA+DHA and HMB Supplementation on Protein Metabolism, Muscle Mass and Functional Capacity in Moderate to Severe COPD
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Weight loss commonly occurs in patients with Chronic Obstructive Pulmonary Disease (COPD), negatively influencing their quality of life, treatment response and survival. Furthermore, limb muscle dysfunction (weakness and/or enhanced fatigue) is a major systemic comorbidity in patients with Chronic Obstructive Pulmonary Disease (COPD), negatively affecting their exercise performance, physical activity, quality of life, and mortality. As nutritional abnormalities are main contributors to muscle loss and dysfunction in COPD, nutritional support is viewed as an essential component of integrated care in these patients.
Although nutritional support is effective in the treatment of weight loss in COPD, attempts to increase muscle mass and function in COPD by supplying large amounts of protein or calories to these patients have been small. This suggests that gains in muscle mass and function are difficult to achieve in COPD unless specific metabolic abnormalities are targeted. The investigators and other researchers found that low muscle mass in COPD was strongly associated with elevated whole body protein turnover and increased myofibrillar protein breakdown rates indicative of muscle contractile protein loss. The investigators have extended this finding recently to normal weight COPD patients characterized by muscle weakness using a more precise and accurate pulse method of tau-methylhistidine tracer.
A substantial number of COPD patients, underweight as well as normal weight to obese, are characterized by an increased inflammatory response as evidenced by elevated levels of the pro-inflammatory cytokines (Tumor Necrosis Factor (TNF)-α, Interleukin (IL) 6 and 8, and the soluble TNF-α receptors (55 and 75). Furthermore, CRP levels are elevated in COPD and associated with reduced quadriceps strength, lower maximal and submaximal exercise capacity and increased morbidity.
One of the few agents capable to suppress the generation of pro-inflammatory cytokines are eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), primary ω-3 fatty acids found in fish oils.
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 weight and muscle mass and function increase was not present or minimal. Also in healthy older adults, fish oil can slow the decline in muscle mass and function. A randomized clinical trial in COPD patients showed that extra nutritional supplementation with PUFAs daily of 1000 mg EPA+DHA as adjunct to exercise training during 8 weeks enhanced exercise capacity but did not lead to muscle mass gain. The patients who did not respond adequately (< 2% gain in weight), had a higher TNF-α level than those who did gain sufficient weight, which is in line with previous data in COPD showing an association between an increased systemic inflammation with non-response to nutritional therapy.
Although previous studies support the concept of EPA+DHA supplementation to ameliorate the systemic inflammatory response and decrease protein breakdown, there is no information present on the effects of EPA+DHA supplementation on whole body and muscle protein metabolism in COPD. The investigators have recently examined the dose-response effects of 0, 2 and 3.5 g of EPA+DHA intervention ( EPA / DHA) for 4 weeks in stable moderate to severe COPD patients (8pts /group) (unpublished data) but were not able to find a positive effect of muscle mass and strength, even with the highest dose, likely related to the relatively short (4 week) supplementation period. The effect of EPA+DHA intervention on whole body and muscle protein synthesis and breakdown rates is currently being analysed.
Although numerous animal studies have shown the benefit of HMB in downregulating muscle protein breakdown under catabolic conditions, there is very little data in COPD patients. Others have tested HMB (3g/d) in COPD patients in the ICU and reported anti-inflammatory benefits and improvement in pulmonary function. In patients with bronchiectasis, 24 week supplementation with an ONS containing HMB (1.5g/d) versus standard of care during pulmonary rehabilitation program, resulted in benefits on body composition, muscle strength and QoL. A combination of HMB and EPA/DHA in a mouse model of cancer cachexia showed a synergy between the two ingredients on preventing muscle loss and downregulation of muscle protein degradation.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Texas
-
College Station, Texas, United States, 77843
- Texas A&M University-CTRAL
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria
- Ability to walk, sit down and stand up independently
- Ability to lie in supine or slightly elevated position for 8.5 hours
- Age 45 - 100
- Clinical diagnosis of COPD, including moderate to very severe chronic airflow limitation, and an FEV1 < 70% of reference FEV1 (GOLD II-III). If subjects are on β2 agonists, only those subjects with <10% improvement in FEV1 will be included.
- 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, including:
- Refraining from intense physical activities (72h) prior to each study visit
- Adhering to fasting state and no smoking from 10 pm ± 2h onwards the day prior to each study visit
Exclusion Criteria
- Participants 86 and older that fail to get physician approval
- Established diagnosis of malignancy
- Established diagnosis of Insulin Dependent 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 nurse that was found during the screening visit, that would interfere with the study or safety of the patient
- BMI ≥ 45 kg/m2
Dietary or lifestyle characteristics:
- Daily use of supplements containing EPA+DHA or HMB prior to the first test day
- Use of protein or amino acid containing nutritional supplements within 5 days of first test day
- Indications related to interaction with study products. Known hypersensitivity to fish and/or shellfish and/or soy
- Use of long-term oral corticosteroids or short course of oral corticosteroids 4 weeks preceding first test day
- Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Fish Oil
2.0 g EPA + DHA / day + placebo powder
|
For Fish oil and Placebo oil, treatment will be provided in capsules.Each group will receive dose distributed to 3 capsules per day.
Participants will be instructed to take all capsules with morning meal. .
For HMB and a placebo powder, product will be delivered as powder taken with water or non-carbonated beverage (like juice).
Product will be provided in 2 sachets/day.
One sachet should be consumed with breakfast and the other prior to bedtime (approx.
10pm).
labeled amino acids L-Phenylalanine (ring-13C6), L-Tyrosine (ring-D4), and tau-Methylhistidine will be infused as a single injection.
Subsequently, the catheter will be used for arterialized venous blood samples (3 ml) drawn multiple through the day
|
Experimental: Fish Oil and HMB
2.0 g EPA + DHA + 3.0 g HMB / day
|
For Fish oil and Placebo oil, treatment will be provided in capsules.Each group will receive dose distributed to 3 capsules per day.
Participants will be instructed to take all capsules with morning meal. .
For HMB and a placebo powder, product will be delivered as powder taken with water or non-carbonated beverage (like juice).
Product will be provided in 2 sachets/day.
One sachet should be consumed with breakfast and the other prior to bedtime (approx.
10pm).
labeled amino acids L-Phenylalanine (ring-13C6), L-Tyrosine (ring-D4), and tau-Methylhistidine will be infused as a single injection.
Subsequently, the catheter will be used for arterialized venous blood samples (3 ml) drawn multiple through the day
|
Placebo Comparator: Placebo
3 g/d soy oil: corn oil (50:50 ratio) + placebo powder
|
For Fish oil and Placebo oil, treatment will be provided in capsules.Each group will receive dose distributed to 3 capsules per day.
Participants will be instructed to take all capsules with morning meal. .
For HMB and a placebo powder, product will be delivered as powder taken with water or non-carbonated beverage (like juice).
Product will be provided in 2 sachets/day.
One sachet should be consumed with breakfast and the other prior to bedtime (approx.
10pm).
labeled amino acids L-Phenylalanine (ring-13C6), L-Tyrosine (ring-D4), and tau-Methylhistidine will be infused as a single injection.
Subsequently, the catheter will be used for arterialized venous blood samples (3 ml) drawn multiple through the day
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes to net whole body protein metabolism
Time Frame: baseline and after 10-week supplementation
|
whole body protein synthesis and myofibrillar protein breakdown measured by labeled amino acids on each study day via blood drawn at time 4, 10, 15, 20, 30, 40, 60, 120, 180, 240 minutes of infusion
|
baseline and after 10-week supplementation
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
muscle mass
Time Frame: 15 minutes on baseline visit, visit at week 5 of supplement intake, and after 10-week supplementation
|
Body composition as measured by Dual-Energy X-ray Absorptiometry
|
15 minutes on baseline visit, visit at week 5 of supplement intake, and after 10-week supplementation
|
limb muscle strength
Time Frame: 15 minutes on baseline visit, visit at week 5 of supplement intake, and after 10-week supplementation
|
kin-com 1-leg test
|
15 minutes on baseline visit, visit at week 5 of supplement intake, and after 10-week supplementation
|
respiratory muscle strength
Time Frame: 15 minutes on baseline visit, visit at week 5 of supplement intake, and after 10-week supplementation
|
Micro-respiratory pressure meter to measure maximum inspiratory and expiratory pressure
|
15 minutes on baseline visit, visit at week 5 of supplement intake, and after 10-week supplementation
|
functional performance via six minute walk test
Time Frame: baseline visit, visit at week 5 of supplement intake, and after 10-week supplementation
|
walk a predetermined loop of 69.77 meters (228.89
feet) at self-selected pace for six minutes
|
baseline visit, visit at week 5 of supplement intake, and after 10-week supplementation
|
systemic inflammatory markers
Time Frame: baseline visit and after 10-week supplementation
|
blood sample will be taken to measure c-reactive protein levels
|
baseline visit and after 10-week supplementation
|
resting energy expenditure
Time Frame: baseline visit and after 10-week supplementation
|
Oxygen consumption and carbon dioxide production will be calculated from the airflow in a transparent plastic (Plexiglas) hood to determine concentration differences between inhaled and exhaled air
|
baseline visit and after 10-week supplementation
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2017-0870
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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