Clinical trial NCT03418376: Carnosine Loading and Periodized Training in MS and HC
Official title: The Impact of Carnosine Loading and Rehabilitation Therapy on Exercise Capacity in Multiple Sclerosis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis
Exercise Therapy
Dietary Supplement
Lead sponsor: Hasselt University
Sponsor class: OTHER
First posted: 2018-02-01
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Twenty multiple sclerosis (MS) patients and twenty healthy controls (HC), aged \>18y will be included following written informed consent. Subjects will be excluded if they experience contraindications to participate in moderate to high intensity exercise or have an EDSS score \>3. First, exercise capacity (maximal graded exercise test) will be evaluated. Heart function will be assessed by an experienced medical doctor, followed by measurement of body composition (DEXA). Maximal strength of the back- and abdominal muscles will be assessed to evaluate core stability. MS patients and HC will be randomly allocated to one of four intervention groups following 6 months of moderate-to-high-intensity cardiovascular exercise therapy with (MSβ, n=10; HCβ, n=10) or without (MSpla, n=10; HCplac, n=10) β-alanine supplementation. Groups not receiving β-alanine supplements, will receive placebo tablets. Following 6 months of exercise training (POST) measurements will be performed similar to baseline.
Primary purpose: OTHER

Brief summary: Increasing evidence favours exercise therapy as an efficient tool to counteract inactivity related secondary symptoms in MS. Furthermore, exercise therapy may affect MS-associated muscle contractile and energy supply dysfunctions. So far, low to moderate intensity exercise rehabilitation has shown to induce small but consistent improvements in several functional parameters. High intensity exercise training in MS seems to further improve this. However, although results are promising, impairments in both muscle contraction and energy supply probably attenuate therapy outcome. In keeping with the above described physiological role of skeletal muscle carnosine and because muscle carnosine content may be lower in MS, the primary aim of the present project is to investigate whether carnosine loading improves exercise therapy outcome (exercise capacity, body composition) and performance in MS. If the latter hypothesis can be confirmed, muscle carnosine loading could be a novel intervention to improve exercise capacity and muscle function in this population.

Detailed description: Pilot data from the (co-)applicants' laboratories suggest that EAE rats (animal MS model) and MS-patients suffer from significantly reduced muscle carnosine levels compared to healthy counterparts. The potential of β-alanine supplementation to elevate muscle carnosine content has been shown in healthy volunteers. Furthermore, the investigators have recently investigated β-alanine and carnosine supplementation in EAE animals. In MS, this has not been investigated yet. Therefore, the researchers' next step is to investigate the impact of β-alanine intake on exercise performance in MS patients. The investigators hypothesize that oral β-alanine supplementation improves exercise therapy outcomes in MS patients.

So far, it is clear that β-alanine intake enhances exercise capacity of untrained, trained and aged individuals by improving contractile properties, maintaining higher intracellular energy levels and optimizing training adaptations. Because early fatigue of contracting musculature during rehabilitation is the predominant cause of exercise cessation, postponing exercise-induced fatigue by β-alanine supplementation will be clinically very relevant (improving exercise therapy efficiency). Consequently, the investigators aim to research the ergogenic potential of β-alanine intake in MS rehabilitation and hypothesize that β-alanine supplementation optimizes exercise therapy outcome (exercise capacity, muscle contractile characteristics) in this population.

Eligibility criteria: Inclusion criteria:

Diagnosis Multiple Sclerosis. Healthy control. Aged \>18y. Written informed consent.

Exclusion criteria:

Contraindications to perform moderate to high intensity exercise. Participation in another study. Experienced acute MS related exacerbation \<6 months prior to start of the study EDSS score \> 3.5

Primary outcomes:
measure: VO2max
timeFrame: Before and after 6 months training (pre vs post)
measure: Serum Lactate
timeFrame: Before and after 6 months training (pre vs post)
measure: Body Composition
timeFrame: Before and after 6 months training (pre vs post)
measure: Strength Assessment Core Musculature
timeFrame: Before and after 6 months training (pre vs post)
measure: Workload
timeFrame: Before and after 6 months training (pre vs post)
Secondary outcomes:
Other outcomes:
Locations:
city: Diepenbeek
country: Belgium
facility: Hasselt University
state: Limburg
Study officials:
affiliation: Hasselt University
name: Bert O Eijnde
role: PRINCIPAL_INVESTIGATOR
References: