<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03803800</url>
  </required_header>
  <id_info>
    <org_study_id>16.111/REVA16.14</org_study_id>
    <nct_id>NCT03803800</nct_id>
  </id_info>
  <brief_title>Periodized Rehabilitation and Beta-alanine Supplementation in Multiple Sclerosis</brief_title>
  <acronym>MSCAR</acronym>
  <official_title>Periodized Rehabilitation and Beta-alanine Supplementation in Multiple Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hasselt University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hasselt University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Exercise therapy and increased physical activity in persons with Multiple Sclerosis (MS)&#xD;
      improves mobility, muscular strength, physical fitness and fatigue without increasing relapse&#xD;
      rate. As such, physical activity and more particular exercise therapy have become an&#xD;
      important part of MS rehabilitation. Despite the fact that the positive effects of exercise&#xD;
      therapy in MS are obvious only 43 percent of the MS community reports to participate in an&#xD;
      exercise program4. Therefore, new exercise therapy approaches that further optimize&#xD;
      rehabilitation, improve exercise adherence and promote participation in physical exercise in&#xD;
      MS are interesting to explore. Therefore, the randomized controlled trial investigates two&#xD;
      types of exercise interventions (classic progressive vs periodized) with or without the&#xD;
      addition of ergogenic supplements (beta-alanine vs placebo).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Following inclusion, baseline measurements (PRE) will be performed in MS patients (n=80).&#xD;
      First, static(isometric) muscle strength (dynamometry), exercise capacity (maximal graded&#xD;
      exercise test) and body composition (DEXA) will be evaluated. After 4 days of recovery, m.&#xD;
      vastus lateralis muscle samples (Bergström procedure) will be taken. Hereafter, MS patients&#xD;
      will be randomly allocated to one of four intervention groups following either 12 weeks of&#xD;
      'classical' moderate intensity cardiovascular exercise therapy (n=40) or periodized exercise&#xD;
      therapy (n=40), with (MSβclassic, n=20; MSβperiod, n=20) or without (MSclassic, n=20;&#xD;
      MSperiod, n=20) β-alanine supplementation. Groups not receiving β-alanine supplements, will&#xD;
      receive placebo tablets that will be identical in taste and appearance. To evaluate post&#xD;
      training fatigue, perceived exertion will be recorded following each training session (6-20&#xD;
      BORG scale). Following 12 weeks of classic or periodized training POST intervention&#xD;
      measurements will be performed similar to baseline.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 9, 2019</start_date>
  <completion_date type="Actual">December 9, 2019</completion_date>
  <primary_completion_date type="Actual">December 1, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Four intervention groups following either 12 weeks of 'classical' moderate intensity cardiovascular exercise therapy (n=40) or periodized exercise therapy (n=40), with (MSβclassic, n=20; MSβperiod, n=20) or without (MSclassic, n=20; MSperiod, n=20) β-alanine supplementation</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>All subjects involved (participants, care providor, asessor) are blinded to the supplementation (beta-alanine vs placebo).&#xD;
Outcome assessors are blinded to the exercise intervention (classic vs periodized training)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Exercise capacity</measure>
    <time_frame>3 weeks</time_frame>
    <description>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®). VO2, VE, RER will be monitored. This test will be performed at least 48 hours separated from the muscle strength test, to prevent interference of muscle fatigue. RER values will be evaluated to verify if the test was performed maximally (RER &gt;1.1).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum lactate</measure>
    <time_frame>3 weeks</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Body composition</measure>
    <time_frame>3 weeks</time_frame>
    <description>hole 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).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Body mass index</measure>
    <time_frame>3 weeks</time_frame>
    <description>Weight (calibrated analogue weight scale) and height will be combined to report BMI in kg/m^2.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Strength measurement</measure>
    <time_frame>3 weeks</time_frame>
    <description>Quadriceps and hamstrings muscle strength will be assessed using a isokinetic dynamometer. 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. This test will be executed in two starting positions (semi-flexed and lumbar isolated) to evaluate adequate co-contraction of m.Iliopsoas and m.Glutei during back flexion and extension respectively.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Muscle carnosine concentration</measure>
    <time_frame>3 weeks</time_frame>
    <description>Muscle biopsies will be obtained from the middle part of the m.vastus lateralis (Bergström needle technique), by an experienced medical doctor.. The first two samples will be immediately embedded in Tissue-Tek, frozen in isopentane cooled with liquid nitrogen and stored at -80°C, until further analysis will be performed. The second two samples will be 'snap freezed' between pincers cooled with liquid nitrogen, and also stored at -80°C until further analysis.&#xD;
Carnosine concentrations will be determined using high-performance liquid chromatography (HPLC). Samples (15mg) are deproteinized using 35% sulfosalicylic acid and centrifuged (5min, 16,000g). Deproteinized supernatant is mixed with AccQ Fluor Borate buffer and reconstituted Fluor Reagent (1:7:2) from the AccQTag chemistry kit (Waters). Derivatized samples are applied to a Waters HPLC system comprised of an AccQTag column (3.9x150mm) and fluorescence detector (excitation/emission wavelength: 250/395nm).</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Classic training &amp; beta-alanine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects following 12 weeks of classic, progressive endurance training, with the addition of ergogenic supplements (beta-alanine supplementation).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Classic training &amp; placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects following 12 weeks of classic, progressive endurance training, without the addition of ergogenic supplements (placebo supplements).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Periodized training &amp; beta-alanine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects following 12 weeks of periodized exercise training, with the addition of ergogenic supplements (beta-alanine supplementation).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Periodized training &amp; placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects following 12 weeks of periodized exercise training, without the addition of ergogenic supplements (placebo supplements).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Classic, progressive endurance training</intervention_name>
    <description>Moderate intensity endurance training will be performed following a sequence of 5 training sessions every 2 weeks throughout the 12-week intervention. Sessions will include 60min of cycling on a stationary bicycle. Exercise intensity will match 60-80% of the maximal heart rate (HRmax)</description>
    <arm_group_label>Classic training &amp; beta-alanine</arm_group_label>
    <arm_group_label>Classic training &amp; placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Periodized exercise training</intervention_name>
    <description>Throughout the 12-week periodized intervention, subjects will perform four recurrent 3-week cycles of moderate endurance training (week 1,three sessions, 60min/session, 60-80% HRmax), high intensity interval training (week 2, three sessions, 10min/session, 3x20sec supramaximal sprint interspersed with recovery intervals of 2min), and recovery weeks (week 3, one high intense interval session as described above)</description>
    <arm_group_label>Periodized training &amp; beta-alanine</arm_group_label>
    <arm_group_label>Periodized training &amp; placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>beta-alanine</intervention_name>
    <description>Some subjects will receive the ergogenic supplement beta-alanine.</description>
    <arm_group_label>Classic training &amp; beta-alanine</arm_group_label>
    <arm_group_label>Periodized training &amp; beta-alanine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Diagnosis Multiple Sclerosis.&#xD;
&#xD;
          -  Healthy control.&#xD;
&#xD;
          -  Aged &gt;18y.&#xD;
&#xD;
          -  Written informed consent.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Contraindications to perform moderate to high intensity exercise.&#xD;
&#xD;
          -  Participation in another study.&#xD;
&#xD;
          -  Experienced acute MS related exacerbation &lt;6 months prior to start of the study&#xD;
&#xD;
          -  EDSS score &gt; 6&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bert O Eijnde</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hasselt</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hasselt University</name>
      <address>
        <city>Diepenbeek</city>
        <state>Limburg</state>
        <zip>3590</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 15, 2019</study_first_posted>
  <last_update_submitted>February 12, 2020</last_update_submitted>
  <last_update_submitted_qc>February 12, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hasselt University</investigator_affiliation>
    <investigator_full_name>Bert Op't Eijnde</investigator_full_name>
    <investigator_title>Prof. Dr.</investigator_title>
  </responsible_party>
  <keyword>Rehabilitation</keyword>
  <keyword>Periodized exercise therapy</keyword>
  <keyword>Ergogenic supplementation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03803800
org study id: 16.111/REVA16.14
nct id: NCT03803800
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Exercise therapy and increased physical activity in persons with Multiple Sclerosis (MS)
      improves mobility, muscular strength, physical fitness and fatigue without increasing relapse
      rate. As such, physical activity and more particular exercise therapy have become an
      important part of MS rehabilitation. Despite the fact that the positive effects of exercise
      therapy in MS are obvious only 43 percent of the MS community reports to participate in an
      exercise program4. Therefore, new exercise therapy approaches that further optimize
      rehabilitation, improve exercise adherence and promote participation in physical exercise in
      MS are interesting to explore. Therefore, the randomized controlled trial investigates two
      types of exercise interventions (classic progressive vs periodized) with or without the
      addition of ergogenic supplements (beta-alanine vs placebo).
Following inclusion, baseline measurements (PRE) will be performed in MS patients (n=80).
      First, static(isometric) muscle strength (dynamometry), exercise capacity (maximal graded
      exercise test) and body composition (DEXA) will be evaluated. After 4 days of recovery, m.
      vastus lateralis muscle samples (Bergström procedure) will be taken. Hereafter, MS patients
      will be randomly allocated to one of four intervention groups following either 12 weeks of
      'classical' moderate intensity cardiovascular exercise therapy (n=40) or periodized exercise
      therapy (n=40), with (MSβclassic, n=20; MSβperiod, n=20) or without (MSclassic, n=20;
      MSperiod, n=20) β-alanine supplementation. Groups not receiving β-alanine supplements, will
      receive placebo tablets that will be identical in taste and appearance. To evaluate post
      training fatigue, perceived exertion will be recorded following each training session (6-20
      BORG scale). Following 12 weeks of classic or periodized training POST intervention
      measurements will be performed similar to baseline.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Four intervention groups following either 12 weeks of 'classical' moderate intensity cardiovascular exercise therapy (n=40) or periodized exercise therapy (n=40), with (MSβclassic, n=20; MSβperiod, n=20) or without (MSclassic, n=20; MSperiod, n=20) β-alanine supplementation
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: All subjects involved (participants, care providor, asessor) are blinded to the supplementation (beta-alanine vs placebo).
Outcome assessors are blinded to the exercise intervention (classic vs periodized training)
measure: Exercise capacity
time frame: 3 weeks
description: 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®). VO2, VE, RER will be monitored. This test will be performed at least 48 hours separated from the muscle strength test, to prevent interference of muscle fatigue. RER values will be evaluated to verify if the test was performed maximally (RER >1.1).
measure: Serum lactate
time frame: 3 weeks
description: 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.
measure: Body composition
time frame: 3 weeks
description: hole 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).
measure: Body mass index
time frame: 3 weeks
description: Weight (calibrated analogue weight scale) and height will be combined to report BMI in kg/m^2.
measure: Strength measurement
time frame: 3 weeks
description: Quadriceps and hamstrings muscle strength will be assessed using a isokinetic dynamometer. 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. This test will be executed in two starting positions (semi-flexed and lumbar isolated) to evaluate adequate co-contraction of m.Iliopsoas and m.Glutei during back flexion and extension respectively.
measure: Muscle carnosine concentration
time frame: 3 weeks
description: Muscle biopsies will be obtained from the middle part of the m.vastus lateralis (Bergström needle technique), by an experienced medical doctor.. The first two samples will be immediately embedded in Tissue-Tek, frozen in isopentane cooled with liquid nitrogen and stored at -80°C, until further analysis will be performed. The second two samples will be 'snap freezed' between pincers cooled with liquid nitrogen, and also stored at -80°C until further analysis.
Carnosine concentrations will be determined using high-performance liquid chromatography (HPLC). Samples (15mg) are deproteinized using 35% sulfosalicylic acid and centrifuged (5min, 16,000g). Deproteinized supernatant is mixed with AccQ Fluor Borate buffer and reconstituted Fluor Reagent (1:7:2) from the AccQTag chemistry kit (Waters). Derivatized samples are applied to a Waters HPLC system comprised of an AccQTag column (3.9x150mm) and fluorescence detector (excitation/emission wavelength: 250/395nm).
arm group label: Classic training & beta-alanine
arm group type: Experimental
description: Subjects following 12 weeks of classic, progressive endurance training, with the addition of ergogenic supplements (beta-alanine supplementation).
arm group label: Classic training & placebo
arm group type: Placebo Comparator
description: Subjects following 12 weeks of classic, progressive endurance training, without the addition of ergogenic supplements (placebo supplements).
arm group label: Periodized training & beta-alanine
arm group type: Experimental
description: Subjects following 12 weeks of periodized exercise training, with the addition of ergogenic supplements (beta-alanine supplementation).
arm group label: Periodized training & placebo
arm group type: Placebo Comparator
description: Subjects following 12 weeks of periodized exercise training, without the addition of ergogenic supplements (placebo supplements).
intervention type: Other
intervention name: Classic, progressive endurance training
description: Moderate intensity endurance training will be performed following a sequence of 5 training sessions every 2 weeks throughout the 12-week intervention. Sessions will include 60min of cycling on a stationary bicycle. Exercise intensity will match 60-80% of the maximal heart rate (HRmax)
arm group label: Classic training & beta-alanine
arm group label: Classic training & placebo
intervention type: Other
intervention name: Periodized exercise training
description: Throughout the 12-week periodized intervention, subjects will perform four recurrent 3-week cycles of moderate endurance training (week 1,three sessions, 60min/session, 60-80% HRmax), high intensity interval training (week 2, three sessions, 10min/session, 3x20sec supramaximal sprint interspersed with recovery intervals of 2min), and recovery weeks (week 3, one high intense interval session as described above)
arm group label: Periodized training & beta-alanine
arm group label: Periodized training & placebo
intervention type: Dietary Supplement
intervention name: beta-alanine
description: Some subjects will receive the ergogenic supplement beta-alanine.
arm group label: Classic training & beta-alanine
arm group label: Periodized training & beta-alanine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Bert O Eijnde
role: Principal Investigator
affiliation: University Hasselt
facility: 
country: Belgium
responsible party type: Principal Investigator
investigator affiliation: Hasselt University
investigator full name: Bert Op't Eijnde
investigator title: Prof. Dr.
mesh term: Multiple Sclerosis
mesh term: Sclerosis