Oral β-Alanine Supplementation in Patients With COPD (BACOPD)

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

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:

1. Investigate baseline muscle carnosine levels to confirm the pilot data in a larger sample of patients with COPD compared with healthy elderly subjects
2. 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
3. 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

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Dietary supplement: beta-alanine; Dietary supplement: placebo; Other: control

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Hasselt, Belgium, 3500
    • Jessa Ziekenhuis (ReGo)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hasselt University
• Collaborators: Jessa Hospital
• Investigators: Principal Investigator: Martijn Spruit, prof. dr., Hasselt University; Study Chair: Jana De Brandt, drs, Hasselt University

Publications and helpful links

General Publications

• De Brandt J, Derave W, Vandenabeele F, Pomies P, Blancquaert L, Keytsman C, Barusso-Gruninger MS, de Lima FF, Hayot M, Spruit MA, Burtin C. Efficacy of 12 weeks oral beta-alanine supplementation in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled trial. J Cachexia Sarcopenia Muscle. 2022 Oct;13(5):2361-2372. doi: 10.1002/jcsm.13048. Epub 2022 Aug 17.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): February 1, 2019
• Study Completion (Actual): February 1, 2019

Study Registration Dates

• First Submitted: May 9, 2016
• First Submitted That Met QC Criteria: May 11, 2016
• First Posted (Estimate): May 12, 2016

Study Record Updates

• Last Update Posted (Actual): February 22, 2019
• Last Update Submitted That Met QC Criteria: February 21, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: BACOPD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided