Carnosine Loading and Periodized Training in MS and HC

NCT03418376 | Completed Results

• 1 other identifier: 17.09/REVA17.02
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis; Exercise Therapy; Dietary Supplement

Outcome Measures

Primary Outcomes (5)

• VO2max

  Exercise capacity will be assessed using a maximal (12-lead ECG) graded cardiopulmonary exercise test (♂: 30W+15W/min, ♀: 20W+10W/min, GE eBike Basic®) with pulmonary gas exchange analysis (Jaeger Oxycon®). VO2max (maximal oxygen uptake) will be monitored. This test will be performed at least 48 hours separated from the muscle strength test, to prevent interference of muscle fatigue. Respiratory exchange ratio (RER) values will be evaluated to verify if the test was performed maximally (RER \>1.1).

  Before and after 6 months training (pre vs post)

• Serum Lactate

  During the exercise test, 2min capillary blood samples will be obtained to analyse blood lactate concentrations (Analox®) and determine the anaerobic threshold before, during and after exercise. Lactate max levels are the maximal concentrations measured during the test, whilst peak Lactate are the lactate concentrations following 2 minutes of rest after cessation of the maximal exercise test.

  Before and after 6 months training (pre vs post)

• Body Composition

  Whole body fat and lean tissue mass will be obtained using Dual Energy X-ray Absorptiometry scan (DEXA) (Hologic Series Delphi-A Fan Beam X-ray Bone Densitometer, Vilvoorde, Belgium). A calibrated analogue weight balance (Seca®) will be used to measure total body mass.

  Before and after 6 months training (pre vs post)

• Strength Assessment Core Musculature

  Back- and abdominal muscle strength will be assessed using an isokinetic dynamometer (System 3, Biodex, ENRAF-NONIUS, New York, USA). After adequate warming-up and movement familiarization, subjects will perform 3 maximal isometric contractions of back- and abdominal muscles for 4-5sec. The peak value of the 3 maximal contractions will be reported (peak back, and peak abdominal muscles).

  Before and after 6 months training (pre vs post)

• Workload

  Exercise capacity will be assessed using a maximal (12-lead ECG) graded cardiopulmonary exercise test (♂: 30W+15W/min, ♀: 20W+10W/min, GE eBike Basic®) with pulmonary gas exchange analysis (Jaeger Oxycon®). VO2max (maximal oxygen uptake) will be monitored. This test will be performed at least 48 hours separated from the muscle strength test, to prevent interference of muscle fatigue. Respiratory exchange ratio (RER) values will be evaluated to verify if the test was performed maximally (RER \>1.1).

  Before and after 6 months training (pre vs post)

Study Arms (4)

MS beta-alanine supplementation

EXPERIMENTAL

Subjects will perform a 6-month exercise intervention and receive beta-alanine supplements.

Dietary Supplement: Beta-alanine supplementation; Other: Exercise intervention

MS placebo group

PLACEBO COMPARATOR

Subjects will perform a 6-month exercise intervention and receive placebo tablets.

Other: Exercise intervention

HC beta-alanine supplementation

EXPERIMENTAL

Subjects will perform a 6-month exercise intervention and receive beta-alanine supplements.

Dietary Supplement: Beta-alanine supplementation; Other: Exercise intervention

HC placebo group

PLACEBO COMPARATOR

Subjects will perform a 6-month exercise intervention and receive placebo tablets.

Other: Exercise intervention

Interventions

Beta-alanine supplementation DIETARY_SUPPLEMENT

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.

HC beta-alanine supplementation; MS beta-alanine supplementation

Exercise intervention OTHER

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.

HC beta-alanine supplementation; HC placebo group; MS beta-alanine supplementation; MS placebo group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hasselt University: lead

Study Sites (1)

Hasselt University

Diepenbeek, Limburg, 3590, Belgium

Location

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Dr. Charly Keytsman
• Organization: Hasselt University

charly.keytsman@uhasselt.be

+32477611122

Study Officials

• Bert O Eijnde

  Hasselt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All parties are blinded regarding the dietary supplement (beta-alanine) or placebo.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.Dr.

Model Details: 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.

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: February 1, 2018
• Study Start: February 1, 2017
• Primary Completion: October 30, 2017
• Study Completion: December 30, 2017
• Last Updated: April 20, 2020
• Results First Posted: April 20, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)