<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/NCT03228550</url>
  </required_header>
  <id_info>
    <org_study_id>002</org_study_id>
    <nct_id>NCT03228550</nct_id>
  </id_info>
  <brief_title>Omega-3 Fatty Acids and Exercise on Mobility and Cognition in Older Women</brief_title>
  <acronym>MOBILE</acronym>
  <official_title>Investigating the Effects of Omega-3 Fatty Acid Multinutrient Supplement and Exercise on Mobility and Cognition in Older Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bournemouth University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Efamol Ltd</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sylvia Waddilove Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Bournemouth University</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>
      The study will provide insight into how lifestyle-related interventions, specifically&#xD;
      nutrition and exercise can impact the health of older women. The study uses a unique&#xD;
      combination of interventions and encapsulates overall health outcomes by measuring both&#xD;
      mobility and cognitive function.&#xD;
&#xD;
      The study examines the effects of a combined omega-3 polyunsaturated fatty acid (PUFA) and&#xD;
      multi-nutrient supplement on measures of mobility and cognition in women aged 60 years and&#xD;
      above. Volunteers for the study will be randomly assigned to one of four groups which are as&#xD;
      follows:&#xD;
&#xD;
        -  Omega-3 PUFA multi-nutrient supplement and aerobic exercise&#xD;
&#xD;
        -  Omega-3 PUFA multi-nutrient supplement and no exercise&#xD;
&#xD;
        -  Placebo supplement and aerobic exercise&#xD;
&#xD;
        -  Placebo supplement and no exercise&#xD;
&#xD;
      Volunteers undertake the dietary supplementation for a period of 24 weeks. The active dietary&#xD;
      supplement contains a daily dosage of 1 g docosahexaenoic acid, 160 mg eicosapentaenoic acid,&#xD;
      240 mg Ginkgo biloba, 60 mg phosphatidylserine, 20 mg d-α tocopherol, 1 mg folic acid, and 20&#xD;
      µg vitamin B12. The placebo supplement contains an iso-calorific oil blend that is typical of&#xD;
      the current UK diet. The aerobic exercise consists of two classes per week the final 12 weeks&#xD;
      of the study on stationary spinning exercise bikes.&#xD;
&#xD;
      Volunteers attend testing at the beginning and after 24 weeks. Verbal memory, spatial working&#xD;
      memory, executive function and processing speed are assessed via a battery of cognitive&#xD;
      tests. Mobility testing comprises three walking tests, some under single and dual task&#xD;
      paradigms, as well as the five times sit to stand test, a measure of dynamic balance and&#xD;
      functional mobility. Volunteers also provide two blood samples, one for fatty acids analysis&#xD;
      and the other serum homocysteine levels. Participants also complete health-related quality of&#xD;
      life questionnaire, the short form 36 (SF36) questionnaire, food diary and food frequency&#xD;
      questionnaire.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Design and Setting:&#xD;
&#xD;
      The study is a randomized semi-blinded, placebo-controlled trial in females aged 60 years and&#xD;
      over. The study examines the effects of a high docosahexaenoic acid omega-3 PUFA&#xD;
      multi-nutrient dietary supplement and aerobic exercise, both on their own and in combination,&#xD;
      on outcomes related to mobility and cognition. All measurements and data collection, as well&#xD;
      as the aerobic exercise, take place at the same study site (Bournemouth University, United&#xD;
      Kingdom), with participants instructed to consume the dietary supplement at home.&#xD;
&#xD;
      Blinding Randomization and Allocation:&#xD;
&#xD;
      The dietary supplements are packed in identical containers and coded by the Principal&#xD;
      Investigator, who has no involvement in the data collection. Omega-3 PUFA capsules have a&#xD;
      distinct odor, therefore a small amount of fish oil is added to the placebo capsules to help&#xD;
      maintain blinding. A stratified block randomization design is followed with stratification&#xD;
      based on frailty classification of non-frail or pre-frail, followed by permuted block&#xD;
      randomization. Randomization is achieved by creating a computer-generated list of numbers&#xD;
      consisting of four blocks for each stratum referred to without specification of the&#xD;
      intervention group (e.g., A, B, C, and D). The list is generated and stored by the Principal&#xD;
      Investigator. Due to the nature of the exercise intervention participants are only be blinded&#xD;
      to the dietary intervention; however, the experimenters are blinded to the exercise group&#xD;
      allocations.&#xD;
&#xD;
      Participants:&#xD;
&#xD;
      Participants are recruited through local newspaper advertisements and public engagements in&#xD;
      Bournemouth, U.K. The public advertisements include a brief study description as well as the&#xD;
      contact details for the research team. Those who are interested receive a participant&#xD;
      information document including the design, procedure, benefits, and risks of the study.&#xD;
      Before any data is collected, all participants provide signed written informed consent forms.&#xD;
&#xD;
      All participants are screened to assess frailty status, according to the Fried et al. (2001)&#xD;
      criteria. The criteria include low muscle strength, self-reported exhaustion, slowed gait&#xD;
      speed, low levels of physical activity, and unintentional weight loss. A score of zero out of&#xD;
      the five indicates non-frail, one or two pre-frail, and three or above frail.&#xD;
&#xD;
      The Mini Mental State Examination (MMSE) is performed to exclude participants with cognitive&#xD;
      impairment, as this has the potential to go undiagnosed. The test is performed according to&#xD;
      British Psychology Society guidelines, and is not used for diagnostic purposes and individual&#xD;
      results are not be disclosed to any participant. Participants who score ≤24 are excluded from&#xD;
      the study.&#xD;
&#xD;
      Demographic Information:&#xD;
&#xD;
      Information on the age, height, weight, verbal intelligence and medication use is collected&#xD;
      from each participant. Information on medications is self-reported, with both type and number&#xD;
      of medications recorded. The national adult reading test (NART) is used to assess verbal&#xD;
      intelligence. The test requires participants to read aloud 50 pre-prepared words, with scores&#xD;
      being calculated based on the number of correct pronunciations. Minor variations from the&#xD;
      pronunciations are not penalized as the aim of the test is to assess familiarity with the&#xD;
      words rather than exact pronunciation.&#xD;
&#xD;
      Sample Size:&#xD;
&#xD;
      Sample size was determined based on the primary outcome of habitual gait speed. The sample&#xD;
      size calculation was based on a difference of 0.08 m/sec with a power of 0.8 and α of 0.05&#xD;
      (two-tailed), based on previous research (Strike et al. 2016). A minimum sample size of 25&#xD;
      participants per group is required to detect an effect size d of 0.8 between experimental&#xD;
      groups and the control. An overall recruitment target of 120 participants, 30 per group has&#xD;
      been set to allow for drop-outs.&#xD;
&#xD;
      Analysis will be carried out on the basis of groups as randomly assigned. This&#xD;
      intention-to-treat analysis will include participants who decide to discontinue treatment,&#xD;
      but take part in assessment at 24 weeks. Data analysis will be performed at the conclusion of&#xD;
      the intervention and include data collected at baseline and 24 weeks. Data will be tested for&#xD;
      normal distribution using Shapiro-Wilk test and Q-Q-plots. Associations between baseline&#xD;
      levels of serum homocysteine, whole-blood DHA levels and cognitive and mobility outcomes will&#xD;
      be made, as well as changes in DHA and measures of mobility and cognition at the end of the&#xD;
      intervention. The treatment effects of the two interventions over time (from pre- and&#xD;
      post-measurements) will be analyzed by 2 X 2 ANOVA, with demographic and health information,&#xD;
      such as age and NART score, and changes in serum homocysteine and changes in blood fatty&#xD;
      acids examined as covariates. This analysis will be performed on all primary and secondary&#xD;
      outcomes. Effect size will also be calculated. In all analyses P&lt;0.05 will be considered&#xD;
      significant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 26, 2017</start_date>
  <completion_date type="Actual">December 31, 2018</completion_date>
  <primary_completion_date type="Actual">December 31, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <intervention_model_description>There are two interventions, a multi-nutrient dietary supplement and exercise. The study will have four groups; 1. multi-nutrient supplement and exercise, 2. multi-nutrient non-exercise, 3. placebo supplement and exercise and 4. placebo supplement non-exercise.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Participants blinded to dietary intervention, but not exercise. Outcomes assessor blinded to both intervention and exercise group.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in habitual gait speed</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Habitual gait speed will be measured using inertial measurement sensors and will be expressed in m/s. Participants will be asked to walk at their normal habitual pace over 13 m. Acceleration and deceleration periods will automatically be excluded from analysis and the measure will be repeated five times with the mean value calculated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in executive function</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Participants draw lines between targets, as rapidly as possible, in a seven by seven grid. There are four different conditions for the task: a numbers condition where targets go from one to forty nine (numbers), a letters condition were the targets go from A to Z followed by letters A to W with an asterisk to signify the letters as the second instance (letters), A condition where participants will alternate between numbers and letters swapping between numbers one to twenty five and letters A to X (numbers-letters) and finally a condition alternating between letters and numbers alternating between letters A to Y and numbers one and twenty four (letters-numbers). Participants will be given 20 s to make as many connections as possible on each task condition. Total number of correct connections will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in verbal memory</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>The Rey's auditory verbal learning test will be used to assess verbal memory. Participants will be read a list of fifteen common words five times. Immediately after each reading, they will recall as many words as possible. Next an interference list will be read containing fifteen different words, after which participants will be asked to recall the original list. In the last trial participants will be asked to recall the original list after a twenty minute delay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in processing speed</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>A variation on the Stroop Test performed on a laptop using Open Sesame software will be used to assess processing speed. During this task a fixation point appears on screen for 500 milliseconds followed by the presentation of the names of one of four colors blue, red, green or white. These words will be presented in four different colors again this could be either blue, red, green or white. Participants will be instructed to identify, as quickly as possible, the color of the text rather than the word displayed on screen and press a designated key on the keyboard for each of the colors. The test is comprised of 144 trials with half of trials having the text and color match and half being a non-match. Processing speed is automatically calculated by the software and is defined as the difference between the mean time taken to respond to the match and non-math trials.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in spatial working memory</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>This task takes place on a laptop using Open Sesame software. Participants are asked to recall the spatial locations of three dots that appear in random locations on screen. The task consists on 10 practice trials followed by 60 recorded trials, with percentage of correct answers being recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fast walking speed</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Fast walking speed will be measured using inertial measurement sensors and results will be expressed in m/s. Participants will be asked to walk as fast as possible over 13 m. Acceleration and deceleration periods will automatically be excluded from analysis and the measure will be repeated five times with the highest value being recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in dual task walking speed</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Dual task walking speed will be measured using inertial measurement sensors and will be expressed in m/s. This task will require participants to walk whilst counting backwards in integers of three from a randomly generated three digit number. This number will be given three seconds before the participant is prompted to start walking. No instruction will be given on prioritization of tasks and the measure will be repeated five times, with the mean gait speed being recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in dual Task Cost</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>The percentage difference between single and dual task performance calculated as = 100* (single-task score - dual-task score)/ single-task</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in five times sit to stand</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>For this task participants will start off seated on a standard chair 44 cm in height from the ground, with their arms folded across their chest and back against the chair. They will be asked to stand up fully from the chair and sit back down again five times, whilst keeping their arms in the same position. This task will be assessed by timing participants from the prompt to start until they reached a seated position on the fifth repetition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in physical functioning from short form 36 questionnaire</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Participants will be asked to complete the short form 36 questionnaire. All questions are multiple choice and scores range from zero to one hundred, with a higher score indicting a greater health status. Items 3-12 are used to assess physical functioning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in bodily pain from short form 36 questionnaire</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Participants will be asked to complete the short form 36 questionnaire. All questions are multiple choice and scores range from zero to one hundred, with a higher score indicting a greater health status. Items 22 and 23 are used to assess bodily pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in role limitations due to physical health problems from short form 36 questionnaire</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Participants will be asked to complete the short form 36 questionnaire. All questions are multiple choice and scores range from zero to one hundred, with a higher score indicting a greater health status. Items 13-16 are used to assess role limitations due to physical health problems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in role limitations due to personal or emotional problems from short form 36 questionnaire</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Participants will be asked to complete the short form 36 questionnaire. All questions are multiple choice and scores range from zero to one hundred, with a higher score indicting a greater health status. Items 17-19 are used to assess role limitations due to personal or emotional problems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in emotional well-being from short form 36 questionnaire</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Participants will be asked to complete the short form 36 questionnaire. All questions are multiple choice and scores range from zero to one hundred, with a higher score indicting a greater health status. Items 24-26, 28 and 30 are used to assess emotional well-being.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in social functioning from short form 36 questionnaire</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Participants will be asked to complete the short form 36 questionnaire. All questions are multiple choice and scores range from zero to one hundred, with a higher score indicting a greater health status. Items 20 and 32 are used to assess social functioning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in energy/fatigue from short form 36 questionnaire</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Participants will be asked to complete the short form 36 questionnaire. All questions are multiple choice and scores range from zero to one hundred, with a higher score indicting a greater health status. Items 23, 27, 29 and 31 are used to assess energy/fatigue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in general health perceptions from short form 36 questionnaire</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Participants will be asked to complete the short form 36 questionnaire. All questions are multiple choice and scores range from zero to one hundred, with a higher score indicting a greater health status. Items 1 and 33-36 are used to assess general health perceptions.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in whole-blood fatty acid content</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Whole-blood fatty acid content will be analyzed from finger-prick samples from non-fasted participants.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in serum homocysteine</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Serum homocysteine levels will be measured by a commercially available enzyme-linked immunosorbent assay (ELISA).</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in stride length</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Change in stride length will be recorded on each gait outcome, using inertial measurement sensors, to give an insight into which aspects of the gait cycle are driving any changes that occur.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in cadence</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Change in cadence will be recorded on each gait outcome, inertial measurement sensors, to give an insight into which aspects of the gait cycle are driving any changes that occur.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in double support phase percentage</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Change in double support phase percentage will be recorded on each gait outcome, inertial measurement sensors, to give an insight into which aspects of the gait cycle are driving any changes that occur.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in stride length variability</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Change in stride length variability will be recorded on each gait outcome, inertial measurement sensors, to give an insight into which aspects of the gait cycle are driving any changes that occur.</description>
  </other_outcome>
  <other_outcome>
    <measure>Physical activity levels</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Physical activity levels will be assessed using the previously validated community health activities program for seniors questionnaire.</description>
  </other_outcome>
  <other_outcome>
    <measure>Dietary energy intake</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Dietary energy intake will be assessed using a estimated three day diet diary. Diet diaries will be analyzed using nutritional composition analysis software and result expressed as kilocalories per day.</description>
  </other_outcome>
  <other_outcome>
    <measure>Carbohydrate intake from diet</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Carbohydrate intake will be assessed using a estimated three day diet diary. Diet diaries will be analyzed using nutritional composition analysis software and result expressed as grams per day.</description>
  </other_outcome>
  <other_outcome>
    <measure>Protein intake from diet</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Protein intake will be assessed using a estimated three day diet diary. Diet diaries will be analyzed using nutritional composition analysis software and result expressed as grams per day.</description>
  </other_outcome>
  <other_outcome>
    <measure>Fat intake from diet</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Fat intake will be assessed using a estimated three day diet diary. Diet diaries will be analyzed using nutritional composition analysis software and result expressed as grams per day.</description>
  </other_outcome>
  <other_outcome>
    <measure>Omega-3 polyunsaturated fatty acid intake from diet</measure>
    <time_frame>Baseline and 24 weeks post intervention</time_frame>
    <description>Omega-3 polyunsaturated fatty acid intake will be assessed using a previously validated 17 item food frequency questionnaire.</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Aging</condition>
  <condition>Cognitive Decline</condition>
  <arm_group>
    <arm_group_label>Efamol Active 50+ and exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Efamol Active 50+ Multinutrient supplement and aerobic exercise</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Efamol Active 50+ and non-exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Efamol Active 50+ Multinutrient supplement and non-aerobic exercise</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo and exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo supplement and aerobic exercise</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo and non-exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo supplement and non- exercise</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Efamol Active 50+</intervention_name>
    <description>1000 mg docosahexaenoic acid, 160 mg eicosapentaenoic acid, 20 µg B12, 1 mg folic acid, 124 mg phosphatidylserine, 240 mg ginkgo biloba standardized leaf extract and 20 mg vitamin E</description>
    <arm_group_label>Efamol Active 50+ and exercise</arm_group_label>
    <arm_group_label>Efamol Active 50+ and non-exercise</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Aerobic exercise</intervention_name>
    <description>Static exercise cycle</description>
    <arm_group_label>Efamol Active 50+ and exercise</arm_group_label>
    <arm_group_label>Placebo and exercise</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo multinutrient</intervention_name>
    <description>Placebo multinutrient supplement</description>
    <arm_group_label>Placebo and exercise</arm_group_label>
    <arm_group_label>Placebo and non-exercise</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Able to walk 50 meters unassisted&#xD;
&#xD;
          -  Non-frail or pre-frail according to Fried frailty phenotype&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Vestibular impairments&#xD;
&#xD;
          -  Diagnosed neurological disorder&#xD;
&#xD;
          -  Mini mental state examination score of ≤24&#xD;
&#xD;
          -  History of lower limb surgery&#xD;
&#xD;
          -  Seafood allergy&#xD;
&#xD;
          -  Regular consumption of multivitamin/fish oil supplements within six months prior to&#xD;
             baseline measurements&#xD;
&#xD;
          -  Previously received advice from a health care professional to not take part in&#xD;
             strenuous exercise.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Female</gender_description>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Simon C Dyall, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Bournemouth University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Fotini Tsofliou, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Bournemouth University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Bournemouth University</name>
      <address>
        <city>Bournemouth</city>
        <state>Dorset</state>
        <zip>BH1 3LT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. doi: 10.1093/gerona/56.3.m146.</citation>
    <PMID>11253156</PMID>
  </reference>
  <reference>
    <citation>Strike SC, Carlisle A, Gibson EL, Dyall SC. A High Omega-3 Fatty Acid Multinutrient Supplement Benefits Cognition and Mobility in Older Women: A Randomized, Double-blind, Placebo-controlled Pilot Study. J Gerontol A Biol Sci Med Sci. 2016 Feb;71(2):236-42. doi: 10.1093/gerona/glv109. Epub 2015 Aug 11.</citation>
    <PMID>26265727</PMID>
  </reference>
  <reference>
    <citation>Dyall SC. Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Front Aging Neurosci. 2015 Apr 21;7:52. doi: 10.3389/fnagi.2015.00052. eCollection 2015.</citation>
    <PMID>25954194</PMID>
  </reference>
  <reference>
    <citation>Dyall SC. Methodological issues and inconsistencies in the field of omega-3 fatty acids research. Prostaglandins Leukot Essent Fatty Acids. 2011 Nov;85(5):281-5. doi: 10.1016/j.plefa.2011.04.009. Epub 2011 Sep 16.</citation>
    <PMID>21925854</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>July 10, 2017</study_first_submitted>
  <study_first_submitted_qc>July 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 25, 2017</study_first_posted>
  <last_update_submitted>January 15, 2019</last_update_submitted>
  <last_update_submitted_qc>January 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 16, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Bournemouth University</investigator_affiliation>
    <investigator_full_name>Simon Dyall</investigator_full_name>
    <investigator_title>Principal Academic</investigator_title>
  </responsible_party>
  <keyword>omega-3 fatty acid</keyword>
  <keyword>B vitamins</keyword>
  <keyword>vitamin E</keyword>
  <keyword>Phosphatidylserine</keyword>
  <keyword>Gingko biloba</keyword>
  <keyword>Gait</keyword>
  <keyword>Aerobic Exercise</keyword>
  <keyword>Memory</keyword>
  <keyword>Cognitive function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03228550
org study id: 002
nct id: NCT03228550
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study will provide insight into how lifestyle-related interventions, specifically
      nutrition and exercise can impact the health of older women. The study uses a unique
      combination of interventions and encapsulates overall health outcomes by measuring both
      mobility and cognitive function.

      The study examines the effects of a combined omega-3 polyunsaturated fatty acid (PUFA) and
      multi-nutrient supplement on measures of mobility and cognition in women aged 60 years and
      above. Volunteers for the study will be randomly assigned to one of four groups which are as
      follows:

        -  Omega-3 PUFA multi-nutrient supplement and aerobic exercise

        -  Omega-3 PUFA multi-nutrient supplement and no exercise

        -  Placebo supplement and aerobic exercise

        -  Placebo supplement and no exercise

      Volunteers undertake the dietary supplementation for a period of 24 weeks. The active dietary
      supplement contains a daily dosage of 1 g docosahexaenoic acid, 160 mg eicosapentaenoic acid,
      240 mg Ginkgo biloba, 60 mg phosphatidylserine, 20 mg d-α tocopherol, 1 mg folic acid, and 20
      µg vitamin B12. The placebo supplement contains an iso-calorific oil blend that is typical of
      the current UK diet. The aerobic exercise consists of two classes per week the final 12 weeks
      of the study on stationary spinning exercise bikes.

      Volunteers attend testing at the beginning and after 24 weeks. Verbal memory, spatial working
      memory, executive function and processing speed are assessed via a battery of cognitive
      tests. Mobility testing comprises three walking tests, some under single and dual task
      paradigms, as well as the five times sit to stand test, a measure of dynamic balance and
      functional mobility. Volunteers also provide two blood samples, one for fatty acids analysis
      and the other serum homocysteine levels. Participants also complete health-related quality of
      life questionnaire, the short form 36 (SF36) questionnaire, food diary and food frequency
      questionnaire.
Design and Setting:

      The study is a randomized semi-blinded, placebo-controlled trial in females aged 60 years and
      over. The study examines the effects of a high docosahexaenoic acid omega-3 PUFA
      multi-nutrient dietary supplement and aerobic exercise, both on their own and in combination,
      on outcomes related to mobility and cognition. All measurements and data collection, as well
      as the aerobic exercise, take place at the same study site (Bournemouth University, United
      Kingdom), with participants instructed to consume the dietary supplement at home.

      Blinding Randomization and Allocation:

      The dietary supplements are packed in identical containers and coded by the Principal
      Investigator, who has no involvement in the data collection. Omega-3 PUFA capsules have a
      distinct odor, therefore a small amount of fish oil is added to the placebo capsules to help
      maintain blinding. A stratified block randomization design is followed with stratification
      based on frailty classification of non-frail or pre-frail, followed by permuted block
      randomization. Randomization is achieved by creating a computer-generated list of numbers
      consisting of four blocks for each stratum referred to without specification of the
      intervention group (e.g., A, B, C, and D). The list is generated and stored by the Principal
      Investigator. Due to the nature of the exercise intervention participants are only be blinded
      to the dietary intervention; however, the experimenters are blinded to the exercise group
      allocations.

      Participants:

      Participants are recruited through local newspaper advertisements and public engagements in
      Bournemouth, U.K. The public advertisements include a brief study description as well as the
      contact details for the research team. Those who are interested receive a participant
      information document including the design, procedure, benefits, and risks of the study.
      Before any data is collected, all participants provide signed written informed consent forms.

      All participants are screened to assess frailty status, according to the Fried et al. (2001)
      criteria. The criteria include low muscle strength, self-reported exhaustion, slowed gait
      speed, low levels of physical activity, and unintentional weight loss. A score of zero out of
      the five indicates non-frail, one or two pre-frail, and three or above frail.

      The Mini Mental State Examination (MMSE) is performed to exclude participants with cognitive
      impairment, as this has the potential to go undiagnosed. The test is performed according to
      British Psychology Society guidelines, and is not used for diagnostic purposes and individual
      results are not be disclosed to any participant. Participants who score ≤24 are excluded from
      the study.

      Demographic Information:

      Information on the age, height, weight, verbal intelligence and medication use is collected
      from each participant. Information on medications is self-reported, with both type and number
      of medications recorded. The national adult reading test (NART) is used to assess verbal
      intelligence. The test requires participants to read aloud 50 pre-prepared words, with scores
      being calculated based on the number of correct pronunciations. Minor variations from the
      pronunciations are not penalized as the aim of the test is to assess familiarity with the
      words rather than exact pronunciation.

      Sample Size:

      Sample size was determined based on the primary outcome of habitual gait speed. The sample
      size calculation was based on a difference of 0.08 m/sec with a power of 0.8 and α of 0.05
      (two-tailed), based on previous research (Strike et al. 2016). A minimum sample size of 25
      participants per group is required to detect an effect size d of 0.8 between experimental
      groups and the control. An overall recruitment target of 120 participants, 30 per group has
      been set to allow for drop-outs.

      Analysis will be carried out on the basis of groups as randomly assigned. This
      intention-to-treat analysis will include participants who decide to discontinue treatment,
      but take part in assessment at 24 weeks. Data analysis will be performed at the conclusion of
      the intervention and include data collected at baseline and 24 weeks. Data will be tested for
      normal distribution using Shapiro-Wilk test and Q-Q-plots. Associations between baseline
      levels of serum homocysteine, whole-blood DHA levels and cognitive and mobility outcomes will
      be made, as well as changes in DHA and measures of mobility and cognition at the end of the
      intervention. The treatment effects of the two interventions over time (from pre- and
      post-measurements) will be analyzed by 2 X 2 ANOVA, with demographic and health information,
      such as age and NART score, and changes in serum homocysteine and changes in blood fatty
      acids examined as covariates. This analysis will be performed on all primary and secondary
      outcomes. Effect size will also be calculated. In all analyses P<0.05 will be considered
      significant.
allocation: Randomized
intervention model: Factorial Assignment
intervention model description: There are two interventions, a multi-nutrient dietary supplement and exercise. The study will have four groups; 1. multi-nutrient supplement and exercise, 2. multi-nutrient non-exercise, 3. placebo supplement and exercise and 4. placebo supplement non-exercise.
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Participants blinded to dietary intervention, but not exercise. Outcomes assessor blinded to both intervention and exercise group.
measure: Change in habitual gait speed
time frame: Baseline and 24 weeks post intervention
description: Habitual gait speed will be measured using inertial measurement sensors and will be expressed in m/s. Participants will be asked to walk at their normal habitual pace over 13 m. Acceleration and deceleration periods will automatically be excluded from analysis and the measure will be repeated five times with the mean value calculated.
measure: Change in executive function
time frame: Baseline and 24 weeks post intervention
description: Participants draw lines between targets, as rapidly as possible, in a seven by seven grid. There are four different conditions for the task: a numbers condition where targets go from one to forty nine (numbers), a letters condition were the targets go from A to Z followed by letters A to W with an asterisk to signify the letters as the second instance (letters), A condition where participants will alternate between numbers and letters swapping between numbers one to twenty five and letters A to X (numbers-letters) and finally a condition alternating between letters and numbers alternating between letters A to Y and numbers one and twenty four (letters-numbers). Participants will be given 20 s to make as many connections as possible on each task condition. Total number of correct connections will be recorded.
measure: Change in verbal memory
time frame: Baseline and 24 weeks post intervention
description: The Rey's auditory verbal learning test will be used to assess verbal memory. Participants will be read a list of fifteen common words five times. Immediately after each reading, they will recall as many words as possible. Next an interference list will be read containing fifteen different words, after which participants will be asked to recall the original list. In the last trial participants will be asked to recall the original list after a twenty minute delay.
measure: Change in processing speed
time frame: Baseline and 24 weeks post intervention
description: A variation on the Stroop Test performed on a laptop using Open Sesame software will be used to assess processing speed. During this task a fixation point appears on screen for 500 milliseconds followed by the presentation of the names of one of four colors blue, red, green or white. These words will be presented in four different colors again this could be either blue, red, green or white. Participants will be instructed to identify, as quickly as possible, the color of the text rather than the word displayed on screen and press a designated key on the keyboard for each of the colors. The test is comprised of 144 trials with half of trials having the text and color match and half being a non-match. Processing speed is automatically calculated by the software and is defined as the difference between the mean time taken to respond to the match and non-math trials.
measure: Change in spatial working memory
time frame: Baseline and 24 weeks post intervention
description: This task takes place on a laptop using Open Sesame software. Participants are asked to recall the spatial locations of three dots that appear in random locations on screen. The task consists on 10 practice trials followed by 60 recorded trials, with percentage of correct answers being recorded.
measure: Change in fast walking speed
time frame: Baseline and 24 weeks post intervention
description: Fast walking speed will be measured using inertial measurement sensors and results will be expressed in m/s. Participants will be asked to walk as fast as possible over 13 m. Acceleration and deceleration periods will automatically be excluded from analysis and the measure will be repeated five times with the highest value being recorded.
measure: Change in dual task walking speed
time frame: Baseline and 24 weeks post intervention
description: Dual task walking speed will be measured using inertial measurement sensors and will be expressed in m/s. This task will require participants to walk whilst counting backwards in integers of three from a randomly generated three digit number. This number will be given three seconds before the participant is prompted to start walking. No instruction will be given on prioritization of tasks and the measure will be repeated five times, with the mean gait speed being recorded.
measure: Change in dual Task Cost
time frame: Baseline and 24 weeks post intervention
description: The percentage difference between single and dual task performance calculated as = 100* (single-task score - dual-task score)/ single-task
measure: Change in five times sit to stand
time frame: Baseline and 24 weeks post intervention
description: For this task participants will start off seated on a standard chair 44 cm in height from the ground, with their arms folded across their chest and back against the chair. They will be asked to stand up fully from the chair and sit back down again five times, whilst keeping their arms in the same position. This task will be assessed by timing participants from the prompt to start until they reached a seated position on the fifth repetition.
measure: Change in physical functioning from short form 36 questionnaire
time frame: Baseline and 24 weeks post intervention
description: Participants will be asked to complete the short form 36 questionnaire. All questions are multiple choice and scores range from zero to one hundred, with a higher score indicting a greater health status. Items 3-12 are used to assess physical functioning.
measure: Change in bodily pain from short form 36 questionnaire
time frame: Baseline and 24 weeks post intervention
description: Participants will be asked to complete the short form 36 questionnaire. All questions are multiple choice and scores range from zero to one hundred, with a higher score indicting a greater health status. Items 22 and 23 are used to assess bodily pain.
measure: Change in role limitations due to physical health problems from short form 36 questionnaire
time frame: Baseline and 24 weeks post intervention
description: Participants will be asked to complete the short form 36 questionnaire. All questions are multiple choice and scores range from zero to one hundred, with a higher score indicting a greater health status. Items 13-16 are used to assess role limitations due to physical health problems.
measure: Change in role limitations due to personal or emotional problems from short form 36 questionnaire
time frame: Baseline and 24 weeks post intervention
description: Participants will be asked to complete the short form 36 questionnaire. All questions are multiple choice and scores range from zero to one hundred, with a higher score indicting a greater health status. Items 17-19 are used to assess role limitations due to personal or emotional problems.
measure: Change in emotional well-being from short form 36 questionnaire
time frame: Baseline and 24 weeks post intervention
description: Participants will be asked to complete the short form 36 questionnaire. All questions are multiple choice and scores range from zero to one hundred, with a higher score indicting a greater health status. Items 24-26, 28 and 30 are used to assess emotional well-being.
measure: Change in social functioning from short form 36 questionnaire
time frame: Baseline and 24 weeks post intervention
description: Participants will be asked to complete the short form 36 questionnaire. All questions are multiple choice and scores range from zero to one hundred, with a higher score indicting a greater health status. Items 20 and 32 are used to assess social functioning.
measure: Change in energy/fatigue from short form 36 questionnaire
time frame: Baseline and 24 weeks post intervention
description: Participants will be asked to complete the short form 36 questionnaire. All questions are multiple choice and scores range from zero to one hundred, with a higher score indicting a greater health status. Items 23, 27, 29 and 31 are used to assess energy/fatigue.
measure: Change in general health perceptions from short form 36 questionnaire
time frame: Baseline and 24 weeks post intervention
description: Participants will be asked to complete the short form 36 questionnaire. All questions are multiple choice and scores range from zero to one hundred, with a higher score indicting a greater health status. Items 1 and 33-36 are used to assess general health perceptions.
measure: Change in whole-blood fatty acid content
time frame: Baseline and 24 weeks post intervention
description: Whole-blood fatty acid content will be analyzed from finger-prick samples from non-fasted participants.
measure: Change in serum homocysteine
time frame: Baseline and 24 weeks post intervention
description: Serum homocysteine levels will be measured by a commercially available enzyme-linked immunosorbent assay (ELISA).
measure: Change in stride length
time frame: Baseline and 24 weeks post intervention
description: Change in stride length will be recorded on each gait outcome, using inertial measurement sensors, to give an insight into which aspects of the gait cycle are driving any changes that occur.
measure: Change in cadence
time frame: Baseline and 24 weeks post intervention
description: Change in cadence will be recorded on each gait outcome, inertial measurement sensors, to give an insight into which aspects of the gait cycle are driving any changes that occur.
measure: Change in double support phase percentage
time frame: Baseline and 24 weeks post intervention
description: Change in double support phase percentage will be recorded on each gait outcome, inertial measurement sensors, to give an insight into which aspects of the gait cycle are driving any changes that occur.
measure: Change in stride length variability
time frame: Baseline and 24 weeks post intervention
description: Change in stride length variability will be recorded on each gait outcome, inertial measurement sensors, to give an insight into which aspects of the gait cycle are driving any changes that occur.
measure: Physical activity levels
time frame: Baseline and 24 weeks post intervention
description: Physical activity levels will be assessed using the previously validated community health activities program for seniors questionnaire.
measure: Dietary energy intake
time frame: Baseline and 24 weeks post intervention
description: Dietary energy intake will be assessed using a estimated three day diet diary. Diet diaries will be analyzed using nutritional composition analysis software and result expressed as kilocalories per day.
measure: Carbohydrate intake from diet
time frame: Baseline and 24 weeks post intervention
description: Carbohydrate intake will be assessed using a estimated three day diet diary. Diet diaries will be analyzed using nutritional composition analysis software and result expressed as grams per day.
measure: Protein intake from diet
time frame: Baseline and 24 weeks post intervention
description: Protein intake will be assessed using a estimated three day diet diary. Diet diaries will be analyzed using nutritional composition analysis software and result expressed as grams per day.
measure: Fat intake from diet
time frame: Baseline and 24 weeks post intervention
description: Fat intake will be assessed using a estimated three day diet diary. Diet diaries will be analyzed using nutritional composition analysis software and result expressed as grams per day.
measure: Omega-3 polyunsaturated fatty acid intake from diet
time frame: Baseline and 24 weeks post intervention
description: Omega-3 polyunsaturated fatty acid intake will be assessed using a previously validated 17 item food frequency questionnaire.
arm group label: Efamol Active 50+ and exercise
arm group type: Experimental
description: Efamol Active 50+ Multinutrient supplement and aerobic exercise
arm group label: Efamol Active 50+ and non-exercise
arm group type: Experimental
description: Efamol Active 50+ Multinutrient supplement and non-aerobic exercise
arm group label: Placebo and exercise
arm group type: Experimental
description: Placebo supplement and aerobic exercise
arm group label: Placebo and non-exercise
arm group type: Experimental
description: Placebo supplement and non- exercise
intervention type: Dietary Supplement
intervention name: Efamol Active 50+
description: 1000 mg docosahexaenoic acid, 160 mg eicosapentaenoic acid, 20 µg B12, 1 mg folic acid, 124 mg phosphatidylserine, 240 mg ginkgo biloba standardized leaf extract and 20 mg vitamin E
arm group label: Efamol Active 50+ and exercise
arm group label: Efamol Active 50+ and non-exercise
intervention type: Behavioral
intervention name: Aerobic exercise
description: Static exercise cycle
arm group label: Efamol Active 50+ and exercise
arm group label: Placebo and exercise
intervention type: Dietary Supplement
intervention name: Placebo multinutrient
description: Placebo multinutrient supplement
arm group label: Placebo and exercise
arm group label: Placebo and non-exercise
criteria: 
gender: Female
gender based: Yes
gender description: Female
minimum age: 60 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Simon C Dyall, PhD
role: Principal Investigator
affiliation: Bournemouth University
last name: Fotini Tsofliou, PhD
role: Study Director
affiliation: Bournemouth University
facility: 
country: United Kingdom
citation: Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. doi: 10.1093/gerona/56.3.m146.
PMID: 11253156
citation: Strike SC, Carlisle A, Gibson EL, Dyall SC. A High Omega-3 Fatty Acid Multinutrient Supplement Benefits Cognition and Mobility in Older Women: A Randomized, Double-blind, Placebo-controlled Pilot Study. J Gerontol A Biol Sci Med Sci. 2016 Feb;71(2):236-42. doi: 10.1093/gerona/glv109. Epub 2015 Aug 11.
PMID: 26265727
citation: Dyall SC. Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Front Aging Neurosci. 2015 Apr 21;7:52. doi: 10.3389/fnagi.2015.00052. eCollection 2015.
PMID: 25954194
citation: Dyall SC. Methodological issues and inconsistencies in the field of omega-3 fatty acids research. Prostaglandins Leukot Essent Fatty Acids. 2011 Nov;85(5):281-5. doi: 10.1016/j.plefa.2011.04.009. Epub 2011 Sep 16.
PMID: 21925854
responsible party type: Principal Investigator
investigator affiliation: Bournemouth University
investigator full name: Simon Dyall
investigator title: Principal Academic
mesh term: Cognitive Dysfunction
sharing ipd: No