Oral β-Alanine Supplementation in Patients With COPD

Study Overview
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Brief Summary
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Preliminary evidence suggest that patients with chronic obstructive pulmonary disease (COPD) suffer from lower-limb muscle dysfunction. This may, at least in part, be due to a combination of physical inactivity and muscle oxidative stress. Pilot data (not published) clearly show that patients with COPD have significantly lower carnosine, which is a pH (acidity-basicity level) buffer and antioxidant, levels in the m. vastus lateralis compared to healthy subjects. Beta-alanine supplementation has shown to increase muscle carnosine in trained and untrained healthy subjects. This study will assess if muscle carnosine can be augmented by beta-alanine supplementation in 40 COPD patients (20 patients receive beta-alanine, 20 patients receive placebo). 10 healthy elderly controls will also be assessed to compare baseline muscle carnosine levels. The aims of this study are to: Investigate baseline muscle carnosine levels to confirm the pilot data in a larger sample of patients with COPD compared with healthy elderly subjects Investigate if beta-alanine supplementation augments muscle carnosine in COPD patients and whether it has an influence on exercise capacity, lower-limb muscle function and quality of life To investigate baseline and post supplementation structural and metabolic muscle characteristics and markers of oxidative stress and inflammation in COPD patients and it's association with muscle carnosine levels

Official Title
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Oral β-Alanine Supplementation in Patients With COPD: Structural, Metabolic and Functional Adaptations

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Dietary Supplement: beta-alanine
* Dietary Supplement: placebo
* Other: control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COPD: diagnosis of moderate to very severe COPD according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines Healthy controls: forced expiratory volume at one second/forced vital capacity (FEV1/FVC) > 0.7, matched for age and gender Exclusion Criteria: The presence of known instable cardiac disease neurological disease and/or musculoskeletal disease that preclude safe participation in an exercise test a history of drugs/alcohol abuse vegetarianism inability to understand the Flemish language. COPD-specific exclusion criteria: COPD exacerbation and/or hospitalization in the last 6 weeks participation in pulmonary rehabilitation in the previous 12 months.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: COPD (beta-alanine)<br> | Dietary Supplement: beta-alanine<br>* Patients receive beta-alanine<br>|
| Placebo Comparator: COPD (placebo)<br> | Dietary Supplement: placebo<br>* Patients receive placebo<br>|
| Other: Healthy controls<br> | Other: control<br>* Healthy controls will be assessed to compare baseline muscle carnosine levels<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| muscle carnosine | by means of high pressure liquid chromatography(HPLC)-analysis of a muscle biopsy | change from baseline to 12 weeks | 
| maximal exercise capacity | by means of an incremental maximal cycle test | change from baseline to 12 weeks | 
| submaximal exercise capacity | by means of a constant-work rate cycle test | change from baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional exercise test 1 | by means of a 6 minutes walk test | change from baseline to 12 weeks | 
| Functional exercise test 2 | by means of a 4 meter gait test | change from baseline to 12 weeks | 
| Muscle function quadriceps | by means of measuring quadriceps (isometric and isokinetic knee extension-flexion) | change from baseline to 12 weeks | 
| Respiratory muscle function | by means of measuring respiratory muscle strength (maximal inspiratory and expiratory pressure) | change from baseline to 12 weeks | 
| Muscle function hand grip | by means of measuring hand grip strength | change from baseline to 12 weeks | 
| Muscle characteristics | Structural and metabolic parameters will be measured with dedicated methodology | change from baseline to 12 weeks | 
| Blood parameters submaximal exercise test | by means of obtaining venous blood before, during and after the constant-work rate cycle test. Blood parameters will be measured with dedicated methodology. | change from baseline to 12 weeks | 
| Blood parameters fasted state | by means of obtaining fasting venous blood. Blood parameters will be measured with dedicated methodology. | change from baseline to 12 weeks | 
| Blood parameters maximal exercise test | by means of obtaining venous blood before and after the maximal cycle test. Blood parameters will be measured with dedicated methodology. | change from baseline to 12 weeks | 
| Comorbidities | by means of Charlson Morbidity index | change from baseline to 12 weeks | 
| Comorbidities: ankle-brachial pressure index | by means of ankle-brachial pressure index | change from baseline to 12 weeks | 
| Comorbidities blood pressure | by means of resting systolic and diastolic blood pressure | change from baseline to 12 weeks | 
| Comorbidities body composition 1 | by means of bio-electrical impedance | change from baseline to 12 weeks | 
| Comorbidities body composition 2 | by means of whole body dual X-ray absorptiometry | change from baseline to 12 weeks | 
| Quality of life: anxiety and depression | by means of the Hospital Anxiety and Depression Scale | change from baseline to 12 weeks | 
| Quality of life: fatigue | by means of the Multidimensional Fatigue Inventory | change from baseline to 12 weeks | 
| Quality of life: dyspnea | by means of the  Modified Medical Research Council (MMRC) dyspnea grade | change from baseline to 12 weeks | 
| Quality of life: general | by means of the Euroqol 5 dimensions (EQ-5D) generic questionnaire | change from baseline to 12 weeks | 
| Quality of life: COPD | by means of the COPD assessment test | change from baseline to 12 weeks | 
| Physical activity: accelerometer | by means of physical activity monitoring via Actigraph (accelerometer) | change from baseline to 12 weeks | 
| Physical activity: questionnaire 1 | by means of physical activity monitoring via Behavioural Regulation in Exercise Questionnaire | change from baseline to 12 weeks | 
| Physical activity: questionnaire 2 | by means of physical activity monitoring via Modified Baecke questionnaire | change from baseline to 12 weeks | 
| Lung function | by means of general pulmonary function (spirometry, long volumes, diffusion capacity for carbon monoxide). | change from baseline to 12 weeks | 
| Heart function | by means of resting ECG testing | change from baseline to 12 weeks |