Eicosapentaenoic Acid and Protein Modulation to Induce Anabolism in Chronic Obstructive Pulmonary Disease (COPD): Aim 2
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Chronic Obstructive Pulmonary Disease, Neurology, Pulmonary |
| Therapuetic Areas: | Neurology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 45 - Any |
| Updated: | 4/17/2018 |
| Start Date: | October 2011 |
| End Date: | April 2019 |
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.
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.
Specific aim 1: To test the hypothesis that supplementation of 3.5g EPA+DHA will increase the
acute net fractional muscle protein synthesis more in COPD patients as compared to healthy
controls in response to a high quality protein supplement.
Specific aim 2: To test the hypothesis that 3.5g/day EPA+DHA for 4 consecutive weeks induces
a higher increase in net fractional muscle protein synthesis in response to a high quality
protein supplement as compared to 2g/day EPA+DHA in COPD patients.
Therefore, to answer the specific aims in this study only the COPD subjects will undergo a
4-week intervention period.
acute net fractional muscle protein synthesis more in COPD patients as compared to healthy
controls in response to a high quality protein supplement.
Specific aim 2: To test the hypothesis that 3.5g/day EPA+DHA for 4 consecutive weeks induces
a higher increase in net fractional muscle protein synthesis in response to a high quality
protein supplement as compared to 2g/day EPA+DHA in COPD patients.
Therefore, to answer the specific aims in this study only the COPD subjects will undergo a
4-week intervention period.
Inclusion Criteria:
Inclusion criteria COPD subjects:
- 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
Inclusion criteria healthy 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 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:
- 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
Exclusion Criteria:
- 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:
- Platelet count (PLT) < 100,000
- History of hypo- or hyper-coagulation disorders including use of a Coumadin
derivative, history of deep venous thrombosis (DVT), or pulmonary embolism (PE)
at any point in lifetime
- Currently taking anti-thrombotics and cannot stop for 7 days (i.e. medical
indication)
- Allergy to local anesthetic
- Use of long-term oral corticosteroids or short course of oral corticosteroids in the
preceding month before enrollment
- Failure to give informed consent or Investigator's uncertainty about the willingness
or ability of the subject to comply with the protocol requirements
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