Nutritional Rehabilitation in Chronic Obstructive Pulmonary Disease (COPD) Patients With Muscle Atrophy

Study Overview
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Brief Summary
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To study in clinically stable Chronic Obstructive Pulmonary Disease (COPD) patients with muscle atrophy: The short-term effects of 4 months exercise training including nutritional supplementation versus exercise training alone on physical functioning (skeletal muscle strength and exercise capacity) and body composition. The long-term effects of 4 months of exercise training and nutritional supplementation followed by 8 months of nutritional counseling (with supplementation on advice) and feedback on physical activity level versus 4 months of exercise training and 8 months with feedback on physical activity level alone on physical functioning, body composition and cardiometabolic risk profile; The cost-effectiveness of exercise rehabilitation and nutritional intervention versus exercise rehabilitation alone.

Detailed Description
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Rationale. Recent guidelines state that pulmonary rehabilitation should be part of integrated care of patients with COPD and not limited to end stage disease. The investigators hypothesize that clinically stable COPD patients muscle atrophy, irrespective of the severity of airflow obstruction, show more pronounced long-term improvement in physical functioning and cardiometabolic risk profile after a rehabilitation programme including nutritional intervention (supplementation and counseling) than after a pulmonary rehabilitation programme without nutritional intervention, at acceptable costs. Nutritional supplementation focuses on enhancing the efficacy of the exercise training. Nutritional counseling aims at maintaining energy balance and modulating cardiovascular disease risk. Study design. The research aims will be addressed in a multi-centre, randomized, clinical trial. Phase A, Rehabilitation (4 months): Group 1: Supervised exercise training and 3 placebo nutritional supplements daily Group 2: Supervised exercise training and 3 nutritional supplements daily Phase B, Maintenance (8 months): Group 1: Exercise counseling (2x) Group 2: Exercise counseling (2x), nutritional counseling (5x) (and 1 nutritional supplement a day on indication) Phase C, Follow-up (3 months): Group 1: no intervention Group 2: 1 nutritional supplement a day on request Nature and extent of the burden and risks associated with participation and benefits. This study aims to tailor pulmonary rehabilitation. Participants of group 1 are visiting their rehabilitation centre 3 times for study related measurements within 15 months (2 times feedback on physical activity, 1 measurement visit). Participants of group 2 will be asked to visit their rehabilitation centre for 6 times (1 measurement visit, 3 times nutritional counseling, 1 time for feedback on physical activity, 1 time for nutritional counseling and feedback on physical activity combined) within 15 months. For both groups baseline measurements and outcome measurements after rehabilitation are already included in the CIRO rehabilitation programme.

Official Title
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Cost Effectiveness Analysis and Clinical Outcome of Nutritional Rehabilitation on Physical Functioning and Cardiometabolic Risk Profile in COPD Patients With Muscle Atrophy

Conditions
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Pulmonary Disease, Chronic Obstructive, Muscular Atrophy

Intervention / Treatment
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* Dietary Supplement: Dietary supplementation
* Dietary Supplement: Placebo supplement
* Behavioral: Nutritional counselling
* Behavioral: Feedback on physical activity level


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic Obstructive Pulmonary Disease Muscle atrophy (a FFMI under the sex- and age-specific 25th percentile FFMI values, assessed by DEXA) Eligible for pulmonary rehabilitation Exclusion Criteria: COPD patients under the age of 18; Allergy or intolerance to fish, milk or other components of the study product; Investigator's uncertainty about the willingness or ability of the patient to comply with the protocol requirements; Not able to stop current supplement use or if total use will be above safe upper limits; Participation in any other study involving investigational or marketed products concomitantly or within two weeks prior to entry into the study; Pregnancy; Life threatening diseases like tuberculosis, carcinoma, AIDS (including HIV+), acute leukaemia etc.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group 1 (placebo control)<br>60 clinically stable COPD patients with muscle atrophy, eligible for out-patient pulmonary rehabilitation | Dietary Supplement: Placebo supplement<br>* Phase A, Rehabilitation (4 months): 3 placebo nutritional supplements daily Phase B, Maintenance (8 months): No supplementation Phase C, Follow-up (3 months): No supplementation<br>* Other names: Non-active supplement;Behavioral: Feedback on physical activity level<br>* Phase A, Rehabilitation (4 months): No exercise counselling Phase B, Maintenance (8 months): Exercise counselling (2x) Phase C, Follow-up (3 months): No exercise counselling Aim: Integration of exercise behaviour into daily routine Improvement of self-regulation skills (e.g. self-monitoring, goal setting, action planning) Increasing adherence/compliance by addressing issues like coping with difficult situation, individual preferences and lifestyle<br>* Other names: Accelerometry;|
| Experimental: Group 2 (nutritional intervention)<br>60 clinically stable COPD patients with muscle atrophy, eligible for out-patient pulmonary rehabilitation | Dietary Supplement: Dietary supplementation<br>* Phase A, Rehabilitation (4 months): 3 nutritional supplements daily Phase B, Maintenance (8 months): nutritional supplementation on advice (1 supplement daily) Phase C, Follow-up (3 months): no supplementation<br>* Other names: Food supplement;Behavioral: Nutritional counselling<br>* Phase A, Rehabilitation (4 months): No counselling Phase B, Maintenance (8 months): Nutritional counselling (4x) Phase C, Follow-up (3 months): No counselling Aim: Optimising dietary intake to physical activity pattern and energy expenditure. Minimize deterioration of dietary intake during acute exacerbations. Optimize dietary lipid profile with respect to total fat intake; trans fatty acids and proportion of poly-unsaturated fatty acids to modulate cardiovascular risk and muscle fatty acid metabolism. Increasing adherence/compliance by addressing issues like taste fatigue, gastro-intestinal symptoms, individual preferences and lifestyle.<br>* Other names: Increasing perceived competence and autonomy;Behavioral: Feedback on physical activity level<br>* Phase A, Rehabilitation (4 months): No exercise counselling Phase B, Maintenance (8 months): Exercise counselling (2x) Phase C, Follow-up (3 months): No exercise counselling Aim: Integration of exercise behaviour into daily routine Improvement of self-regulation skills (e.g. self-monitoring, goal setting, action planning) Increasing adherence/compliance by addressing issues like coping with difficult situation, individual preferences and lifestyle<br>* Other names: Accelerometry;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal muscle strength | Skeletal muscle strength assessed by isokinetic dynamometry (Biodex®) | 0, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiometabolic risk profile | lipid profile (blood) systemic inflammatory profile (blood) blood pressure(hematometer) HOMA index (blood) visceral fat mass (DEXA) AGEs skin (AGE reader) | 0, 4, 12 months | 
| Health related quality of life | Assessed by: SGRQ: Saint George Respiratory Questionnaire SF36: Short Form - 36 EQ5D: EuroQol 5 domains, extended with energy/fatique domain | 0, 4, 12, 15 months | 
| Dyspnoea | Assessed by: -MRC-index: Medical Research Council dyspnoea scale | 0, 4, 12, 15 months | 
| Body composition | Assessed by - DEXA scan | 0, 4, 12 months | 
| Exercise capacity | Assessed by: - Constant Work Rate Test (CWRT) | 0, 4, 12 months | 
| Plasma levels of supplemented (micro)nutrients | Assessed by: Plasma amino acids (leucine) Vitamin D (plasma calcidiol 25(OH)D ) | 0, 4, 12 months | 
| Bone mass density | Assessed by: - DEXA scan | 0, 4, 12 months | 
| Physical activity | Assessed by: - Accelerometry | 0, 4, 12, 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Disease, Chronic Obstructive, Muscular Atrophy, Nutritional rehabilitation, Counselling