<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/NCT03792711</url>
  </required_header>
  <id_info>
    <org_study_id>ANTW1701</org_study_id>
    <nct_id>NCT03792711</nct_id>
  </id_info>
  <brief_title>The Effects of the Oral Nutritional Supplement With β-hydroxy-β-methylbutyrate in Lean Body Mass Among Taiwan Elderly</brief_title>
  <official_title>A Controlled, Open-label, Parallel-group, Randomized Study to Evaluate the Effects of Additional Oral Nutritional Supplement With β-hydroxy-β-methylbutyrate on Thigh Muscle Mass in Older People With Pre-frail Status in Taiwan</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Yang Ming University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Yang Ming 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>
      Primary objective:&#xD;
&#xD;
      To evaluate the effects of additional oral nutritional supplement containing&#xD;
      β-hydroxy-β-methylbutyrate (HMB) on thigh muscle mass in elderly subjects with pre-frail&#xD;
      status&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
        1. To evaluate the effects of additional oral nutritional supplement containing&#xD;
           β-hydroxy-β-methylbutyrate on physical performance, nutrition status, and quality of&#xD;
           life in elderly subjects with pre-frail status&#xD;
&#xD;
        2. To determine the safety profile of additional oral nutritional supplement containing&#xD;
           β-hydroxy-β-methylbutyrate in elderly subjects with pre-frail status&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a controlled, open-label, parallel-group, randomized, investigator initiated study to&#xD;
      evaluate the effectiveness of oral nutritional supplement containing&#xD;
      β-hydroxy-β-methylbutyrate (Ensure® Plus Advance) on thigh muscle mass and physical&#xD;
      performance in elderly subjects with pre-frail status. The study is planned to enroll a total&#xD;
      of 70 elderly subjects with pre-frail status defined by Fried's criteria with modified cutoff&#xD;
      values as suggested by Asian Working Group for Sarcopenia (AWGS) for Asian population. The&#xD;
      subject to be enrolled will meet the phenotypic definition of pre-frail for one or two of&#xD;
      five phenotypic criteria: weakness as measured by grip strength, slow walking speed, low&#xD;
      level of physical activity, self-reported exhaustion, and unintentional weight loss.&#xD;
&#xD;
      After obtaining informed consent and the confirmation of eligibility, subjects will be&#xD;
      randomized into the HMB or control group in a 1:1 ratio. All enrolled subjects will be under&#xD;
      standard care, which is mainly dietary consultation for healthy aging by dietitians to assure&#xD;
      sufficient dietary protein intake in all subjects. Subjects assigned to the HMB group will&#xD;
      consume 2 bottles of Ensure® Plus Advance per day for 12 weeks additionally, while subjects&#xD;
      assigned to the control group will not receive any placebo or active control.&#xD;
&#xD;
      In this study, subjects will be requested for a total of 4 visits at the clinical site,&#xD;
      including screening visit, Visit 1 for randomization, Visit 2 at Week 6, and Visit 3 at Week&#xD;
      12 (end of study/EOS). The telephone visit will be scheduled at Week 3 and Week 9 to&#xD;
      follow-up with subjects.&#xD;
&#xD;
      Thigh muscle mass of all subjects will be evaluated by MRI. The physical performance of&#xD;
      subjects will be determined by short physical performance battery (SPPB) and handgrip&#xD;
      strength. The nutrition status of subjects will be measured by MNA® -SF and nutrition&#xD;
      biomarkers, including serum albumin, pre-albumin, 25-hydroxy-vitamin D, vitamin B12, and&#xD;
      C-reactive protein (CRP). SF-36v2™ Health Survey will be used to evaluate the quality of life&#xD;
      of subjects. The safety profile of Ensure® Plus Advance will be determined by monitoring the&#xD;
      adverse event (AE/SAE) during the study period. Blood samples of each subject will be&#xD;
      collected at Visits 1, 2 and 3 for analysis of nutrition biomarkers. There will be a total of&#xD;
      approximately 30 mL of blood to be collected from each subject during the study period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 18, 2019</start_date>
  <completion_date type="Actual">December 30, 2020</completion_date>
  <primary_completion_date type="Actual">December 30, 2020</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>lean body mass</measure>
    <time_frame>3 months</time_frame>
    <description>Thigh muscle mass (kg) will be measured by MRI and be further analyzed at Visits 1 and 3 (EOS/ET). The data assessed at Visit 1 will be the baseline. The summary results of thigh muscle mass (kg) at the baseline and subsequent visits, and the change from baseline will be summarized descriptively by groups.&#xD;
Changes from baseline within each group will be tested by paired t-test or Wilcoxon signed-rank test with a significance level of 0.05. The change from baseline between groups will be analyzed by two sample t-test or Wilcoxon rank-sum test.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">70</enrollment>
  <condition>Frail Elderly Syndrome</condition>
  <condition>Nutrition Disorders in Old Age</condition>
  <condition>Muscle Loss</condition>
  <arm_group>
    <arm_group_label>HMB group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 servings (440 mL)/day Ensure® Plus Advance for use as a supplement with or between meals</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Standard of care includes mainly dietary consultation for healthy aging by dietitians to reach sufficient dietary protein intake.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Ensure® Plus Advance</intervention_name>
    <description>Previous studies suggest that protein supplementation is an effective dietary strategy to decrease frailty by positively influence the weight loss or sarcopenia in elderly.&#xD;
Lean body mass includes all body tissue except fat and is well recognized to be associated with an increased risk of morbidity and mortality. Oral nutrition supplements have been shown to increase food intake and body weight, but not lean body mass. In previous studies, β-hydroxy-β-methylbutyrate, which is leucine metabolite, has been shown to enhance protein synthesis and decrease protein degradation leading to increase lean body mass. It showed that β-hydroxy-β-methylbutyrate supplement with exercise increased lean body mass in health elderly population and improved the physical performance in elderly women.</description>
    <arm_group_label>HMB group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects have to meet ALL inclusion criteria to be eligible for participation in the study.&#xD;
&#xD;
          1. Male or female subject with age between 65-80 years old (inclusive)&#xD;
&#xD;
          2. Subject with pre-frail status, which is defined by Fried's criteria&#xD;
&#xD;
          3. Subject who can fully communicate, understand the study, and provide the informed&#xD;
             consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects who meet ANY of the following exclusion criteria will be excluded from the study.&#xD;
&#xD;
          1. Subject with BMI &gt; 35 kg/m2&#xD;
&#xD;
          2. Subject with active diseases judged by the investigator as below&#xD;
&#xD;
               1. Recent stroke (within 6 months prior to screening)&#xD;
&#xD;
               2. Parkinsonism&#xD;
&#xD;
               3. Motor neuron disease&#xD;
&#xD;
               4. Uncontrolled cardiovascular disease&#xD;
&#xD;
               5. Uncontrolled chronic obstructive pulmonary disease&#xD;
&#xD;
               6. Chronic kidney disease severe than Stage IIIb&#xD;
&#xD;
               7. Dementia or other mental illness with cognitive impairment&#xD;
&#xD;
               8. Uncontrolled depression&#xD;
&#xD;
               9. Chronic and acute infection&#xD;
&#xD;
              10. Uncontrolled metabolic diseases including type II diabetes mellitus&#xD;
&#xD;
              11. Thyroid disease, including hypothyroidism and hyperthyroidism&#xD;
&#xD;
              12. Uncontrolled gastrointestinal disease (inflammatory bowel disease, Crohn's&#xD;
                  disease, etc)&#xD;
&#xD;
          3. Subject with a history or evidence of malignancy in the past 5 years (except for&#xD;
             non-melanoma skin neoplasia)&#xD;
&#xD;
          4. Subject using any dietary supplementation containing β-hydroxy-β-methylbutyrate within&#xD;
             1 month prior to screening&#xD;
&#xD;
          5. Subject using Ensure® plus Advance within 1 month prior to screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Liang-Kung Chen, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of Health Policy and Welfare, National Yang-Ming University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Taiwan Association of Integrated Care</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>December 11, 2018</study_first_submitted>
  <study_first_submitted_qc>January 2, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 3, 2019</study_first_posted>
  <last_update_submitted>April 7, 2022</last_update_submitted>
  <last_update_submitted_qc>April 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nutrition Disorders</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/NCT03792711
org study id: ANTW1701
nct id: NCT03792711
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Primary objective:

      To evaluate the effects of additional oral nutritional supplement containing
      β-hydroxy-β-methylbutyrate (HMB) on thigh muscle mass in elderly subjects with pre-frail
      status

      Secondary objectives:

        1. To evaluate the effects of additional oral nutritional supplement containing
           β-hydroxy-β-methylbutyrate on physical performance, nutrition status, and quality of
           life in elderly subjects with pre-frail status

        2. To determine the safety profile of additional oral nutritional supplement containing
           β-hydroxy-β-methylbutyrate in elderly subjects with pre-frail status
This is a controlled, open-label, parallel-group, randomized, investigator initiated study to
      evaluate the effectiveness of oral nutritional supplement containing
      β-hydroxy-β-methylbutyrate (Ensure® Plus Advance) on thigh muscle mass and physical
      performance in elderly subjects with pre-frail status. The study is planned to enroll a total
      of 70 elderly subjects with pre-frail status defined by Fried's criteria with modified cutoff
      values as suggested by Asian Working Group for Sarcopenia (AWGS) for Asian population. The
      subject to be enrolled will meet the phenotypic definition of pre-frail for one or two of
      five phenotypic criteria: weakness as measured by grip strength, slow walking speed, low
      level of physical activity, self-reported exhaustion, and unintentional weight loss.

      After obtaining informed consent and the confirmation of eligibility, subjects will be
      randomized into the HMB or control group in a 1:1 ratio. All enrolled subjects will be under
      standard care, which is mainly dietary consultation for healthy aging by dietitians to assure
      sufficient dietary protein intake in all subjects. Subjects assigned to the HMB group will
      consume 2 bottles of Ensure® Plus Advance per day for 12 weeks additionally, while subjects
      assigned to the control group will not receive any placebo or active control.

      In this study, subjects will be requested for a total of 4 visits at the clinical site,
      including screening visit, Visit 1 for randomization, Visit 2 at Week 6, and Visit 3 at Week
      12 (end of study/EOS). The telephone visit will be scheduled at Week 3 and Week 9 to
      follow-up with subjects.

      Thigh muscle mass of all subjects will be evaluated by MRI. The physical performance of
      subjects will be determined by short physical performance battery (SPPB) and handgrip
      strength. The nutrition status of subjects will be measured by MNA® -SF and nutrition
      biomarkers, including serum albumin, pre-albumin, 25-hydroxy-vitamin D, vitamin B12, and
      C-reactive protein (CRP). SF-36v2™ Health Survey will be used to evaluate the quality of life
      of subjects. The safety profile of Ensure® Plus Advance will be determined by monitoring the
      adverse event (AE/SAE) during the study period. Blood samples of each subject will be
      collected at Visits 1, 2 and 3 for analysis of nutrition biomarkers. There will be a total of
      approximately 30 mL of blood to be collected from each subject during the study period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: lean body mass
time frame: 3 months
description: Thigh muscle mass (kg) will be measured by MRI and be further analyzed at Visits 1 and 3 (EOS/ET). The data assessed at Visit 1 will be the baseline. The summary results of thigh muscle mass (kg) at the baseline and subsequent visits, and the change from baseline will be summarized descriptively by groups.
Changes from baseline within each group will be tested by paired t-test or Wilcoxon signed-rank test with a significance level of 0.05. The change from baseline between groups will be analyzed by two sample t-test or Wilcoxon rank-sum test.
arm group label: HMB group
arm group type: Experimental
description: 2 servings (440 mL)/day Ensure® Plus Advance for use as a supplement with or between meals
arm group label: Control group
arm group type: No Intervention
description: Standard of care includes mainly dietary consultation for healthy aging by dietitians to reach sufficient dietary protein intake.
intervention type: Dietary Supplement
intervention name: Ensure® Plus Advance
description: Previous studies suggest that protein supplementation is an effective dietary strategy to decrease frailty by positively influence the weight loss or sarcopenia in elderly.
Lean body mass includes all body tissue except fat and is well recognized to be associated with an increased risk of morbidity and mortality. Oral nutrition supplements have been shown to increase food intake and body weight, but not lean body mass. In previous studies, β-hydroxy-β-methylbutyrate, which is leucine metabolite, has been shown to enhance protein synthesis and decrease protein degradation leading to increase lean body mass. It showed that β-hydroxy-β-methylbutyrate supplement with exercise increased lean body mass in health elderly population and improved the physical performance in elderly women.
arm group label: HMB group
criteria: 
gender: All
minimum age: 65 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Liang-Kung Chen, PhD
role: Principal Investigator
affiliation: Institute of Health Policy and Welfare, National Yang-Ming University
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Nutrition Disorders