The primary objective is to compare the effects of daily beta-alanine supplementation or a placebo supplement on exercise tolerance (cycle endurance time). The secondary objectives are:1) To compare the effects of daily oral beta-alanine…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Exercise tolerance, defined as the change in cycle endurance time (before and
after the rehabilitation period), measured during a constant work rate cycle
test (CWRT)
Secondary outcome
Lower-limb muscle function, 6-minute walking distance, fatigue, disease
specific quality of life, body composition, dyspnoea, symptoms of anxiety and
depression, physical activity, problematic activities of daily life, mobility,
cognitive function, respiratory muscle strength, systemic beta-alanine,
carnosine, taurine and histidine, systemic inflammatory and oxidative stress
markers, muscle beta-alanine, carnosine, taurine and histidine, muscle
inflammation and oxidative stress and inflammatory and oxidative stress markers
in the lungs, therapy adherence, patient safety and supplement duration.
Background summary
Physical inactivity and oxidative stress have been identified as the two main
causes of reduced quadriceps muscle strength and endurance, two well-known
disabling extra-pulmonary features in patients with COPD. In healthy untrained
elderly subjects, oral beta-alanine supplementation (without training) is
powerful in increasing muscle carnosine content and exercise capacity by
13-29%. It is very plausible to hypothesize that increased muscle carnosine
levels will have a positive effect on lower-limb muscle function and exercise
tolerance in COPD, by buffering pH and scavenging Reactive Oxygen Species
(ROS). To date, neuromuscular electrical stimulation (NMES) is one of the best
strategies to improve lower-limb muscle function and exercise tolerance in COPD
patients with explicit functional limitations and high symptom burden. These
patients also receive resistance training 1-2 times per day, as part of
standard care to further improve lower-limb muscle function and exercise
tolerance. Beta-alanine supplementation is expected to augment the effects of
NMES-based pulmonary rehabilitation on exercise tolerance, lower-limb muscle
function, oxidative stress, fatigue, physical activity, and quality of life in
COPD patients.
Study objective
The primary objective is to compare the effects of daily beta-alanine
supplementation or a placebo supplement on exercise tolerance (cycle endurance
time).
The secondary objectives are:
1) To compare the effects of daily oral beta-alanine supplementation or a
placebo supplement in patients with COPD on: lower-limb muscle function,
6-minute walking distance, fatigue, disease specific quality of life, body
composition, dyspnoea, symptoms of anxiety and depression, physical activity,
problematic activities of daily life, mobility, cognitive function, respiratory
muscle strength, systemic beta-alanine, carnosine, taurine and histidine,
systemic inflammatory and oxidative stress markers, muscle beta-alanine,
carnosine, taurine and histidine, muscle inflammation and oxidative stress,
inflammatory and oxidative stress markers in the lungs, patient safety and
therapy adherence.
2) To evaluate whether there is a correlation between changes in muscle
beta-alanine/carnosine levels and changes in exercise tolerance, lower-limb
muscle function, systemic inflammatory and oxidative stress markers, muscle
inflammation and oxidative stress, inflammatory and oxidative stress markers in
the lungs.
Study design
Prospective, randomized, double-blind, placebo-controlled study
Intervention
Oral beta-alanine supplementation (sustained-release Carnosyn®; 3.2 g/day) or
placebo for 8-10 weeks.
Study burden and risks
BURDEN: In addition to standard care (NMES and resistance training, as part of
regular pulmonary rehabilitation program at CIRO), participants are asked to
perform additional measurements (venous blood sampling, vastus lateralis muscle
biopsy (optional, not required), cognitive function tests (M-WCST and SCWT),
and pulmonary function tests (NO-measurement) on 2 separate days in total (1
before intervention and 1 after intervention). Furthermore, participants have
to take supplements on a daily basis for 8-10 weeks.
RISKS: The proposed dose of sustained release beta-alanine (SR Carnosyn®; 3.2
g/day) is proven effective, without any side-effects. Complications of vastus
lateralis muscle biopsy may include infection, bleeding and hematoma formation.
These complications are rare (<1.5%) if the test is performed properly under
semi-sterile conditions. Venous blood sampling is associated with a 5% risk of
developing local haemorrhage. However, this will disappear within 2 weeks and
is not associated with (functional) limitations.
BENEFIT: Irrespective of treatment allocation, both groups will benefit from
participating in the pulmonary rehabilitation program. Beta-alanine is known to
be effective in increasing muscle carnosine content in both healthy young
adults and elderly subjects, with subsequent improvement in their exercise
tolerance and has the potential to reduce oxidative stress and improve
cognitive function.
GROUP RELATEDNESS: This will be the first study in which oral beta-alanine
supplementation will be combined with a pulmonary rehabilitation program in
COPD patients
Hornerheide 1
Horn 6085 NM
NL
Hornerheide 1
Horn 6085 NM
NL
Listed location countries
Age
Inclusion criteria
- COPD, GOLD group B or D (high symptomatic)
- Grade 3 or higher on the Modified Medical Research Council (mMRC) dyspnoea
scale
- Clinically stable according to the pulmonary physician, i.e. no exacerbation
and/or hospitalization within the previous 4 weeks.
- Age between 40-80 years
- Cycle endurance time, measured during a constant work rate test (CWRT) at 75%
of the peak cycling load, is 100-300 seconds and/or Quadriceps Muscle Strength
(peak torque), measured with a computerized dynamometer, is less than 80% of
the predicted value
- Attending the regular inpatient pulmonary rehabilitation program in CIRO and
receiving NMES as the primary muscle training modality.
- No use of anabolic steroids during the inpatient pulmonary rehabilitation
program in CIRO
Exclusion criteria
- Instable cardiac disease
- Neurological disease and/or musculoskeletal disease that preclude safe
participation in an exercise test
- History of drugs/alcohol abuse in the past 10 years
- Vegetarianism
- Inability to understand the Dutch language
- Self-reported β-alanine supplementation in the past 3 months
- Participation in pulmonary rehabilitation within the past 12 months
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL68757.091.19 |