<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/NCT03815201</url>
  </required_header>
  <id_info>
    <org_study_id>BasqueHS</org_study_id>
    <nct_id>NCT03815201</nct_id>
  </id_info>
  <brief_title>Protein Supplementation and Muscle Function in the Elderly</brief_title>
  <official_title>Effects of a Combined Physical Training and Protein Supplementation Intervention on Muscle Mass, Functional and Cognitive Performance, and Health-related Quality of Life in the Elderly: a Randomized Controlled Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Basque Health Service</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of the Basque Country (UPV/EHU)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Universitario de Álava</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Basque Health Service</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Sarcopenia is a geriatric syndrome associated with functional lost and disability, leading to&#xD;
      an increase in healthcare costs. Physical activity, especially multicomponent exercise&#xD;
      program, seems to be the most effective intervention to delay disability in elderly patients.&#xD;
&#xD;
      The main objective of the current study is to determine if leucine-enriched protein ingestion&#xD;
      after exercise training helps to increase muscle mass gains. Secondary outcomes will be to&#xD;
      analyse the different effects among cognitive performance, depressive symptoms, disability,&#xD;
      inflammation, quality of life and use of healthcare services.&#xD;
&#xD;
      A randomized controlled trial will be carried out to assess the objectives of the current&#xD;
      study. Participants will be randomized into two different groups (N=40, each one): an&#xD;
      exercise training control group and exercise training plus leucine-enriched protein ingestion&#xD;
      intervention group. Exercise training will take 12 weeks of supervised training intervention&#xD;
      and 12 weeks of non-supervised training intervention for both groups. Biological samples will&#xD;
      be analysed in Biodonostia Health Research Institute and in the University of the Basque&#xD;
      Country (UPV/EHU).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study protocol: Acute hospitalised, community-dwelling elderly patients will be recruited at&#xD;
      internal medicine service of the Araba University Hospital (HUA). Patients that fulfil&#xD;
      eligibility criteria for the study will be evaluated during their hospitalization for&#xD;
      different aspects (Hospital Evaluation): handgrip, nutritional assessment using Mini&#xD;
      Nutritional Assessment- Short Form Test (MNA-SF), functional assessment by Short Physical&#xD;
      Performance Battery (SPPB), cognitive assessment (Pfeiffer test) and frailty assessment&#xD;
      (Fried test). Once hospital evaluation is assessed patients will be offered to participate in&#xD;
      the study. In case patients accept to participate, another assessment will be carried out on&#xD;
      discharge date (Discharge Day Evaluation): handgrip, functional assessment (SPPB), 30-Second&#xD;
      Chair Stand Test, 30-Second Arm Curl Test, the Timed Up ang Go (TUG) Test, 8 Foot Up and Go&#xD;
      (FUG) Test, Gait Speed Test for 4- meters and for 8-meters. Patients will also take two&#xD;
      accelerometers, a wrist accelerometer and a hip accelerometer, for a week.&#xD;
&#xD;
      A week after discharge day, patients will again be evaluated (Laboratory 1 (Lab 1) evaluation&#xD;
      day): the same tests of discharge day will be repeated plus Berg Scale and 6-Minute Walking&#xD;
      Test. Then, patients will wait until a group of 5-6 participants is formed. As soon as&#xD;
      patients accept to participate, and when all evaluation tests involved until Lab 1 evaluation&#xD;
      day are completed, participants will be randomized into two different groups: exercise&#xD;
      training plus placebo control group (Group 1) and exercise training plus leucine-enriched&#xD;
      protein ingestion intervention group (Group 2).&#xD;
&#xD;
      Participants will be called by telephone a week before the intervention starts for&#xD;
      psychological assessment, blood analysis and Dual Energy X-ray Absorptiometry (DEXA)&#xD;
      assessment.&#xD;
&#xD;
      The first day of intervention program all participants will be evaluated for nutritional&#xD;
      assessment: Mini Nutritional Assessment (MNA) Test, a quantitative score (14-item) of&#xD;
      adherence to the Mediterranean diet (Prevention with Mediterranean Diet (PREDIMED)&#xD;
      questionnaire), two non-consecutive 24-hour dietary recall and anthropometry.&#xD;
&#xD;
      Exercise training intervention will be divided into supervised intervention and&#xD;
      non-supervised intervention for both groups. Supervised intervention program will take 12&#xD;
      weeks and participants will have to assist 2 non-consecutive days per week to hospital for&#xD;
      1-hour exercise training. After those 12 weeks participants will take two accelerometers, a&#xD;
      wrist accelerometer and a hip accelerometer, for a week. After that week participants will&#xD;
      have to assist 2 non-consecutive days on the same week to complete: the same physical tests&#xD;
      of Lab 1 evaluation day, anthropometry and nutritional tests, blood analysis and DEXA&#xD;
      assessment. Individualised physical exercise recommendations will be explained and given to&#xD;
      participants for the following 12 weeks of non-supervised intervention. During those weeks of&#xD;
      non-supervised intervention, telephone monitoring will be made every two weeks.&#xD;
&#xD;
      When completing the study, at week 24, participants will be called by telephone to come to&#xD;
      hospital for blood analysis, psychological assessment, nutritional tests and one 24-hour&#xD;
      dietary recall, and to take the two accelerometers for a week. After a week, participants&#xD;
      will be evaluated for physical assessment (the same physical tests of Lab 1 evaluation day&#xD;
      will be carried out) and a second 24-hour dietary recall and anthropometry will be assessed.&#xD;
&#xD;
      The placebo and leucine-enriched protein supplementation will only be taken during supervised&#xD;
      training period twice a week after 1-hour exercise training is completed. Participants will&#xD;
      ignore what the supplement is, as the mixtures will be codified.&#xD;
&#xD;
      Protein supplementation will consist on 20gr of whey protein (a commercial preparation of&#xD;
      Davisco®: BiPRO all-natural whey protein isolate) enriched with 3g of leucine (commercially&#xD;
      prepared by Nutricia), and protein mixture will be diluted with 100ml of water. The placebo&#xD;
      will be an energy-matched mixture.&#xD;
&#xD;
      The samples will be store at the Basque Biobank and then will be send to Biodonostia Health&#xD;
      Research Institute for their analysis.&#xD;
&#xD;
      Sample size: power calculation has been done for the main variable: muscle mass increase. If&#xD;
      35 people are recruited on each group, a difference of unless 1.5 to 2kg will be detected in&#xD;
      muscle mass with a standard deviation of 1.5-1.7kg and &gt;80% of power, and an alfa level of&#xD;
      0.05. Taking into account that mortality can be about 30%, 40 participants will be recruited&#xD;
      for each group.&#xD;
&#xD;
      Statistical analysis: variance analysis will be used to analyse the continuous variables and&#xD;
      the Chi-square test for the categorical variables, both analyses will be used for the&#xD;
      cross-cutting analysis. To evaluate the training effect on the primary and secondary&#xD;
      variables general linear models will be used. Age and the pre-intervention value of any&#xD;
      primary or secondary variable will be considered as covariates. The effect size and the&#xD;
      statistical significance level for each of these effects will be calculated: group effect&#xD;
      (between subjects), time effect (intra-subjects) and group*time interaction. Other possible&#xD;
      interactions between group*sex and all other variables of the study will be determined. The&#xD;
      analyses will be adjusted by multiple comparison test and the intend to treat principle will&#xD;
      be applied for all analyses. For the analysis of missing data, such as for the participants&#xD;
      that drop out from the program or did not meet the study criteria, different imputation&#xD;
      methods will be used, and sensitivity analysis will be applied.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 31, 2017</start_date>
  <completion_date type="Anticipated">January 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">January 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>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>muscle mass change</measure>
    <time_frame>change from baseline muscle mass assessment to 12 weeks of supervised intervention</time_frame>
    <description>muscle mass measured using dual-energy x-ray absorptiometry method</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Physical fitness change</measure>
    <time_frame>change from baseline assessment to 12 weeks of supervised intervention and to the end of the study (at 6 months)</time_frame>
    <description>combination of different tests to assess physical fitness</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">41</enrollment>
  <condition>Sarcopenia</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>exercise training program: 2 non-consecutive days per week during 12 weeks plus placebo ingestion post-training</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>exercise training program: 2 non-consecutive days per week during 12 weeks plus leucine-enriched protein supplementation post-training</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Group 2</intervention_name>
    <description>leucine-enriched protein supplementation during the first 1/2 hour post-training</description>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Group 1</intervention_name>
    <description>placebo, an energy-matched mixture, during the first 1/2 hour post-training</description>
    <arm_group_label>Group 1</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age: &gt; 70 years&#xD;
&#xD;
          -  Punctuation at the Mini Mental State Questionnaire (MMSE): &gt; or = 20.&#xD;
&#xD;
          -  Any patient that fulfill the European Working Group on Sarcopenia in Older People&#xD;
             (EWGSOP) criteria for sarcopenia diagnosis.&#xD;
&#xD;
          -  Anyone who is able to walk alone, to walk using a walking stick or a walking frame, or&#xD;
             to walk using parallel walking bars.&#xD;
&#xD;
          -  Anyone able to understand the instructions or what is being said.&#xD;
&#xD;
          -  Anyone signing the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic kidney disease&#xD;
&#xD;
          -  To have suffered a heart attack in the last 3 months.&#xD;
&#xD;
          -  To be unable to walk.&#xD;
&#xD;
          -  To have suffered any fracture of the upper or lower limbs in the last 3 months.&#xD;
&#xD;
          -  Anyone suffering from severe dementia.&#xD;
&#xD;
          -  Autoimmune neuromuscular disorders (for example, myasthenia gravis, Guillain-Barré&#xD;
             syndrome, inflammatory myopathies) or amyotrophic lateral sclerosis.&#xD;
&#xD;
          -  Anyone refusing to sign the informed consent, or anyone who does not agree to the&#xD;
             study protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>70 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ariadna Besga</last_name>
    <role>Principal Investigator</role>
    <affiliation>Basque Health Service</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Maria Amasene</last_name>
    <phone>945007728</phone>
    <email>mamasene001@ehu.eus</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Iñaki Echeverria</last_name>
    <email>inaki.echeverriag@ehu.eus</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hospital Santiago Apostol</name>
      <address>
        <city>Vitoria-Gasteiz</city>
        <state>Alava</state>
        <zip>1004</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ariadna Besga</last_name>
      <phone>945007728</phone>
      <email>ariadna.besgabasterra@osakidetza.eus</email>
    </contact>
    <contact_backup>
      <last_name>Maria Amasene</last_name>
      <email>mamasene001@ehu.eus</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 15, 2019</study_first_submitted>
  <study_first_submitted_qc>January 21, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>January 21, 2019</last_update_submitted>
  <last_update_submitted_qc>January 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 24, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Basque Health Service</investigator_affiliation>
    <investigator_full_name>Ariadna Besga</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>muscle mass</keyword>
  <keyword>protein supplementation</keyword>
  <keyword>leucine</keyword>
  <keyword>elderly</keyword>
  <keyword>exercise training</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcopenia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
  </patient_data>
  <!-- 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/NCT03815201
org study id: BasqueHS
nct id: NCT03815201
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Sarcopenia is a geriatric syndrome associated with functional lost and disability, leading to
      an increase in healthcare costs. Physical activity, especially multicomponent exercise
      program, seems to be the most effective intervention to delay disability in elderly patients.

      The main objective of the current study is to determine if leucine-enriched protein ingestion
      after exercise training helps to increase muscle mass gains. Secondary outcomes will be to
      analyse the different effects among cognitive performance, depressive symptoms, disability,
      inflammation, quality of life and use of healthcare services.

      A randomized controlled trial will be carried out to assess the objectives of the current
      study. Participants will be randomized into two different groups (N=40, each one): an
      exercise training control group and exercise training plus leucine-enriched protein ingestion
      intervention group. Exercise training will take 12 weeks of supervised training intervention
      and 12 weeks of non-supervised training intervention for both groups. Biological samples will
      be analysed in Biodonostia Health Research Institute and in the University of the Basque
      Country (UPV/EHU).
Study protocol: Acute hospitalised, community-dwelling elderly patients will be recruited at
      internal medicine service of the Araba University Hospital (HUA). Patients that fulfil
      eligibility criteria for the study will be evaluated during their hospitalization for
      different aspects (Hospital Evaluation): handgrip, nutritional assessment using Mini
      Nutritional Assessment- Short Form Test (MNA-SF), functional assessment by Short Physical
      Performance Battery (SPPB), cognitive assessment (Pfeiffer test) and frailty assessment
      (Fried test). Once hospital evaluation is assessed patients will be offered to participate in
      the study. In case patients accept to participate, another assessment will be carried out on
      discharge date (Discharge Day Evaluation): handgrip, functional assessment (SPPB), 30-Second
      Chair Stand Test, 30-Second Arm Curl Test, the Timed Up ang Go (TUG) Test, 8 Foot Up and Go
      (FUG) Test, Gait Speed Test for 4- meters and for 8-meters. Patients will also take two
      accelerometers, a wrist accelerometer and a hip accelerometer, for a week.

      A week after discharge day, patients will again be evaluated (Laboratory 1 (Lab 1) evaluation
      day): the same tests of discharge day will be repeated plus Berg Scale and 6-Minute Walking
      Test. Then, patients will wait until a group of 5-6 participants is formed. As soon as
      patients accept to participate, and when all evaluation tests involved until Lab 1 evaluation
      day are completed, participants will be randomized into two different groups: exercise
      training plus placebo control group (Group 1) and exercise training plus leucine-enriched
      protein ingestion intervention group (Group 2).

      Participants will be called by telephone a week before the intervention starts for
      psychological assessment, blood analysis and Dual Energy X-ray Absorptiometry (DEXA)
      assessment.

      The first day of intervention program all participants will be evaluated for nutritional
      assessment: Mini Nutritional Assessment (MNA) Test, a quantitative score (14-item) of
      adherence to the Mediterranean diet (Prevention with Mediterranean Diet (PREDIMED)
      questionnaire), two non-consecutive 24-hour dietary recall and anthropometry.

      Exercise training intervention will be divided into supervised intervention and
      non-supervised intervention for both groups. Supervised intervention program will take 12
      weeks and participants will have to assist 2 non-consecutive days per week to hospital for
      1-hour exercise training. After those 12 weeks participants will take two accelerometers, a
      wrist accelerometer and a hip accelerometer, for a week. After that week participants will
      have to assist 2 non-consecutive days on the same week to complete: the same physical tests
      of Lab 1 evaluation day, anthropometry and nutritional tests, blood analysis and DEXA
      assessment. Individualised physical exercise recommendations will be explained and given to
      participants for the following 12 weeks of non-supervised intervention. During those weeks of
      non-supervised intervention, telephone monitoring will be made every two weeks.

      When completing the study, at week 24, participants will be called by telephone to come to
      hospital for blood analysis, psychological assessment, nutritional tests and one 24-hour
      dietary recall, and to take the two accelerometers for a week. After a week, participants
      will be evaluated for physical assessment (the same physical tests of Lab 1 evaluation day
      will be carried out) and a second 24-hour dietary recall and anthropometry will be assessed.

      The placebo and leucine-enriched protein supplementation will only be taken during supervised
      training period twice a week after 1-hour exercise training is completed. Participants will
      ignore what the supplement is, as the mixtures will be codified.

      Protein supplementation will consist on 20gr of whey protein (a commercial preparation of
      Davisco®: BiPRO all-natural whey protein isolate) enriched with 3g of leucine (commercially
      prepared by Nutricia), and protein mixture will be diluted with 100ml of water. The placebo
      will be an energy-matched mixture.

      The samples will be store at the Basque Biobank and then will be send to Biodonostia Health
      Research Institute for their analysis.

      Sample size: power calculation has been done for the main variable: muscle mass increase. If
      35 people are recruited on each group, a difference of unless 1.5 to 2kg will be detected in
      muscle mass with a standard deviation of 1.5-1.7kg and >80% of power, and an alfa level of
      0.05. Taking into account that mortality can be about 30%, 40 participants will be recruited
      for each group.

      Statistical analysis: variance analysis will be used to analyse the continuous variables and
      the Chi-square test for the categorical variables, both analyses will be used for the
      cross-cutting analysis. To evaluate the training effect on the primary and secondary
      variables general linear models will be used. Age and the pre-intervention value of any
      primary or secondary variable will be considered as covariates. The effect size and the
      statistical significance level for each of these effects will be calculated: group effect
      (between subjects), time effect (intra-subjects) and group*time interaction. Other possible
      interactions between group*sex and all other variables of the study will be determined. The
      analyses will be adjusted by multiple comparison test and the intend to treat principle will
      be applied for all analyses. For the analysis of missing data, such as for the participants
      that drop out from the program or did not meet the study criteria, different imputation
      methods will be used, and sensitivity analysis will be applied.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Single (Participant)
measure: muscle mass change
time frame: change from baseline muscle mass assessment to 12 weeks of supervised intervention
description: muscle mass measured using dual-energy x-ray absorptiometry method
measure: Physical fitness change
time frame: change from baseline assessment to 12 weeks of supervised intervention and to the end of the study (at 6 months)
description: combination of different tests to assess physical fitness
arm group label: Group 1
arm group type: Placebo Comparator
description: exercise training program: 2 non-consecutive days per week during 12 weeks plus placebo ingestion post-training
arm group label: Group 2
arm group type: Active Comparator
description: exercise training program: 2 non-consecutive days per week during 12 weeks plus leucine-enriched protein supplementation post-training
intervention type: Dietary Supplement
intervention name: Group 2
description: leucine-enriched protein supplementation during the first 1/2 hour post-training
arm group label: Group 2
intervention type: Other
intervention name: Group 1
description: placebo, an energy-matched mixture, during the first 1/2 hour post-training
arm group label: Group 1
criteria: 
gender: All
minimum age: 70 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Ariadna Besga
role: Principal Investigator
affiliation: Basque Health Service
last name: Maria Amasene
phone: 945007728
email: mamasene001@ehu.eus
last name: Iñaki Echeverria
email: inaki.echeverriag@ehu.eus
facility: 
status: Recruiting
contact: 
contact backup: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Basque Health Service
investigator full name: Ariadna Besga
investigator title: Principal Investigator
mesh term: Sarcopenia
sharing ipd: Yes
ipd info type: Study Protocol
ipd info type: Clinical Study Report (CSR)