Disturbances in BCAA Metabolism and the Effects of Feeding and Exercise in COPD

Study Overview
=================
Brief Summary
-----------------
Studies on resting human muscle show that ingestion of the branched-chain amino acids (BCAA): leucine, valine and isoleucine have an anabolic effect on muscle protein metabolism. However, the effects of BCAA intake on protein metabolism during exercise are less clear. When BCAA were supplied as single amino acids, without other amino acids and/or carbohydrates, no effects were observed on protein kinetics. On the other hand, ingestion of BCAA during running appeared to reduce the catabolic effect of running on muscle protein metabolism. These experiments were all performed with mixtures of the BCAA with or without carbohydrates but not in the form of complete meals with food protein as a basis. Therefore, it is still unknown whether a protein meal, containing a substantial amount of BCAA is beneficial during exercise by inducing an anabolic effect. Whey and Casein protein contain a substantial amount of BCAA in contrast to Soy protein. Therefore, it is hypothesized that milk-based proteins are a better and more physiological source of BCAA during exercise and will lead to more protein anabolism. Most of the available studies have been carried out in young and fit humans but there are hardly any data are available in the increasing population of the elderly. Therefore it is still unknown whether a BCAA rich protein meal can enhance the anabolic effect of exercise in older individuals. Besides sarcopenia, a substantial part of the elderly is suffering from a chronic systemic disease such as chronic obstructive pulmonary disease (COPD). COPD represents an important health care problem. COPD is the fourth leading cause of death and will be the third leading cause worldwide in 2020. Besides the local impairment, COPD is a chronic wasting disease, associated with alterations in intermediary metabolism. Substantial disturbances have been found in BCAA (and related) metabolism in these patients at rest and during exercise. It might therefore be of clinical relevance to study the metabolic effects of BCAA rich protein meals in patients with COPD at rest and during exercise.

Detailed Description
-----------------
In this study we investigate whether milk based protein sources of BCAA (casein and whey proteins) are superior to soy protein in the stimulation of protein anabolism before, during and after cycle exercise in COPD and healthy elderly and young subjects, and whether adding BCAA to soy protein will increase protein anabolism in these subjects. To investigate Leucine, Isoleucine and Valine metabolism during and after exercise in COPD and healthy subjects

Official Title
-----------------
The Effects of Exercise on the Metabolic Fate of Branched Chain Amino Acids in Relation to Aging and Chronic Disease.

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Dietary Supplement: Caseinate
* Dietary Supplement: Whey protein isolate
* Dietary Supplement: Soy
* Dietary Supplement: soy+BCAA


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Irreversible chronic airflow limitation (FEV1 <70% of predicted) Clinically stable condition Exclusion Criteria: Oxygen supplementation Respiratory tract infection or exacerbation of his disease at least 4 weeks prior to the study Oral corticosteroids as maintenance medication Other concomitant metabolic disease (ie malignancy, cardiac failure, recent surgery, severe endocrine, hepatic or renal disorder)

Ages Eligible for Study
-----------------
Minimum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Caseinate protein intake<br>18 mg protein/kg body weight caseinate and 46 mg maltodextrin / kg body weight per 20 min sip feeding | Dietary Supplement: Caseinate<br>* 18 mg protein/kg body weight caseinate and 46 mg maltodextrin / kg body weight per 20 min sip feeding<br>* Other names: casein;|
| Experimental: Whey protein isolate intake<br>18 mg protein/kg body weight whey protein isolate and 46 mg maltodextrin / kg body weight per 20 min sip feeding | Dietary Supplement: Whey protein isolate<br>* 18 mg protein/kg body weight whey protein isolate and 46 mg maltodextrin / kg body weight per 20 min sip feeding<br>* Other names: Whey;|
| Experimental: Soy protein intake<br>18 mg protein/kg body weight soy and 46 mg maltodextrin / kg body weight per 20 min sip feeding | Dietary Supplement: Soy<br>* 18 mg protein/kg body weight soy and 46 mg maltodextrin / kg body weight per 20 min sip feeding<br>|
| Experimental: soy+BCAA protein intake<br>18 mg protein/kg body weight soy+BCAA and 46 mg maltodextrin / kg body weight per 20 min sip feeding | Dietary Supplement: soy+BCAA<br>* 18 mg protein/kg body weight soy+BCAA and 46 mg maltodextrin / kg body weight per 20 min sip feeding<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Net whole body protein synthesis | Net whole body protein synthesis during protein feeding and the response to a 20 min cycle exercise bout | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in whole body protein synthesis rate | Whole body protein synthesis rate during protein feeding and the response to 20 min cycle exercise bout | 6 hours | 
| Change in Leucine turnover | Leucine turnover during protein feeding and the response to a 20 min cycle exercise bout | 6 hours | 
| Change in Isoleucine turnover | Isoleucine turnover during protein feeding and the response to a 20 min cycle exercise bout | 6 hours | 
| Change in Valine turnover | Valine turnover during protein feeding and the response to a 20 min cycle exercise bout | 6 hours | 
| Change in plasma lactate concentration | Plasma lactate during protein feeding and the response to a 20 min cycle exercise bout | 6 hours | 
| Change in NH3 concentration | Plasma NH3 during protein feeding and the response to a 20 min cycle exercise bout | 6 hours | 
| Change in plasma amino acids concentrations | Plasma amino acid concentrations during protein feeding and the response to a 20 min cycle exercise bout | 6 hours | 
| Splanchnic extraction of amino acids during protein feeding | Splanchnic extraction of amino acids during protein feeding and the response to a 20 min cycle exercise bout | 6 hours | 
| Change in whole body protein breakdown rate | Whole body protein breakdown rate during protein feeding and the response to cycle exercise | 6 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COPD, protein metabolism, branched-chain amino acid metabolism, exercise, protein feeding