Carnosine Loading and Periodized Training in MS and HC
Condition: Multiple Sclerosis; Exercise Therapy; Dietary Supplement
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional

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.
    

Intervention name(s): Beta-alanine supplementation; Exercise intervention
Intervention type(s): Dietary Supplement; Other
Intervention description(s): The supplementation protocol of β-alanine (Etixx® Omega Pharma Belgium NV) involves oral intake of 4 x 800mg (3.2g/day29, 43) daily with at least 2h apart of slow-release β-alanine during the first 12 weeks. After this loading period, subjects will receive a maintenance dose of 2 x 800mg (1.6g/day) β-alanine for the remaining study duration.; The exercise training program (6 months) involves 3 week cycles (week I-III). During week I, subjects will perform high volume moderate intensity cardiovascular cycle training (3x/week). Twice a week, subjects perform 3h training sessions (70-80% HRmax*) and once a week a 1.5h session will be executed (80-90% HRmax). During week II, subjects will perform low volume maximum intensity interval cycle training (3/w). High intensity interval cycle training (HIIT) will consist of 3x maximal sprints (90-100% HRmax) of 1.5min, interspersed with 3min rest intervals. A 5min standardized warming up and 5min cooling down will be performed. Week III involves a recovery week where subjects will perform one training session of 1.5h at an exercise intensity of 70-80% HRmax and one session of HIIT.
Allocation: Randomized
Intervention model: Parallel Assignment
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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other