<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/NCT03256929</url>
  </required_header>
  <id_info>
    <org_study_id>SHAMIRMB</org_study_id>
    <nct_id>NCT03256929</nct_id>
  </id_info>
  <brief_title>Personalized Diet-driven Microbiota Alterations as a Tool for Improving Mood Status in Elderly</brief_title>
  <official_title>Personalized Diet-driven Microbiota Alterations as a Tool for Improving Mood Status in Elderly</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tel Hai College</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shamir Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Clalit Health Services</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Migal, Galilee Technology Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Tel Hai College</source>
  <oversight_info>
    <has_dmc>Yes</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 propose of the study is a multi-disciplinary project connecting nutritional and health&#xD;
      sciences with social and behavioral sciences, and aimed at understanding the microbiota&#xD;
      changes related to the third age and their effects on mood and mental health. The research&#xD;
      aims are primarily practical: They will explore the influence of the gut flora on depression,&#xD;
      which could help us to recommend diets that might reduce the risk of developing depression.&#xD;
      The novelty of this proposal is in the design of personalized diet-driven microbiota&#xD;
      alterations and health status to modulate depression in elderly. For the first time the&#xD;
      improvement of mental health in the elderly will be studied through a nutritional and food&#xD;
      habits approach based on microbiota changes upon ageing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Depressive symptoms are highly prevalent in older populations, is one of the most serious&#xD;
      public health problems faced by modern societies. The problems caused by depression, such as&#xD;
      functional impairments, lead to decreased quality of life, poor recovery from illnesses and&#xD;
      increased mortality in the elderly. Researchers have found that there are many possible&#xD;
      connections between personal or physical variables and the risk of developing depression; it&#xD;
      can be caused by sociodemographic factors, or cognitive and functional impairment,&#xD;
      nutritional status is also related to development of depression.&#xD;
&#xD;
      Recent studies have suggested that depressive symptoms are more prevalent in individuals with&#xD;
      impaired nutritional status. The intestinal microbial population (microbiota), known&#xD;
      influenced by several factors including nutrition, age, and stress.&#xD;
&#xD;
      The microbiota is essential to human health, changes in composition microbiota play a role in&#xD;
      metabolic, nutritional, physiological and immunological processes in the human body, recently&#xD;
      reported also behavioral changes associated with anxiety and depression. The aging process is&#xD;
      characterized by a decrease intestinal transit time, as a result of dental problems, decrease&#xD;
      in saliva activity, and efficiency of digestion and absorption leading to changes in the&#xD;
      microbiota composition, which causes an increase in sensitivity to the development of chronic&#xD;
      and inflammatory diseases. Although other factors undoubtedly contribute to mental health&#xD;
      decline in the elderly, the association of the intestinal microbiota of older people with&#xD;
      inflammation, the clear association between diet and microbiota and the recent report on the&#xD;
      correlation between changes in microbiota and depression have led us to hypothesize that diet&#xD;
      can shape microbiota, which then affect mood status in older people and decreased depressive&#xD;
      symptoms.&#xD;
&#xD;
      The purpose of the study is to examine the effect of a custom diet based on the composition&#xD;
      of the intestinal bacterial population (compared with a diet for a healthy lifestyle that is&#xD;
      not based on a microbiotic profile), on moods and depression among the elderly.&#xD;
&#xD;
      Before and after the intervention, several tests will be carried out, using stool sample for&#xD;
      microbiota analysis, salivary cortisol measurement and clinical information (GDS, life style&#xD;
      habits, CEBQ, FFQ), These measures will indicate participants' clinical, nutritional and&#xD;
      mental situation before and after in order to probe the diet intervention impact on&#xD;
      microbiota and its correlation to mental health.&#xD;
&#xD;
      The infrastructure of this research includes several aspects - mood, health and nutrition&#xD;
      status that are main parameters in life quality of the third age, and the research is based&#xD;
      on the complementary cooperation of social and behavior sciences and nutrition and life&#xD;
      sciences experts.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 11, 2017</start_date>
  <completion_date type="Anticipated">February 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">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>
    <intervention_model_description>The first stage will be mapping all of the aged population of the research area, who will be interviewed (after receiving their consent) in order to determine those who are depressed. 200 depressed and pre-depression individuals (according to the GDS) will be chosen, and divided randomly into two groups- one will undergo the diet- driven microbiota adjustment personalized-intervention (nutrition advisory), and the other will get general information on nutrition and health .</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mental health status - Depression</measure>
    <time_frame>1 year</time_frame>
    <description>Depression will be assessed using the Geriatric Depression Scale (GDS). changes in test score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Microbiota profile</measure>
    <time_frame>1 year</time_frame>
    <description>Microbiota composition will be characterized from feces. The stool specimens will be collected and immediately put in buffer and stored at -20ºC for analysis and then will be kept at -80ºC in a locked freezer. The very low temperature is of significance to avoid variability in the stool bacterial composition and to preserve bacterial DNA in fecal samples. Total microbial DNA will be extracted using the PowerSoil DNA extraction kit (MoBio) and then submitted to 16S rRNA gene amplicon sequencing using paired end Illumina technology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Salivary Cortisol</measure>
    <time_frame>1 year</time_frame>
    <description>Salivary Cortisol Measurement - The sampling procedure is simple and non-invasive. The saliva sample will be collected by using the Salivettes and freezed as is. On the day of the assay, Salivette™ samples can be thawed and then centrifuged at low speed to separate the saliva sample from the gauze. The cortisol in saliva is remarkably stable and will be measured by the salivary cortisol kit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>life style habits</measure>
    <time_frame>1 year</time_frame>
    <description>The life style habits questionnaire is based on MABAT ZAHAV, National Health and Nutrition Survey (Aged 60 and over) 2005-2006, Ministry of Health, Israel and includes demographic details, questions on health status, dental health, functional, cognitive and emotional states, use of medications and nutrition supplements, alcohol consumption, physical activity, smoking habits, eating and dieting patterns, nutritional knowledge and attitudes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nutritional data collection - Food Frequency Questionnaire - FFQ</measure>
    <time_frame>1 year</time_frame>
    <description>Habitual dietary intake information that will be assessed using the Food Frequency Questionnaire (FFQ)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Eating Behavior Questionnaire - CEBQ</measure>
    <time_frame>1 year</time_frame>
    <description>Appetite, gastrointestinal problems, and chewing and swallowing problems will be assessed using the Composite Eating Behavior Questionnaire (CEBQ)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Anthropometric measure 1</measure>
    <time_frame>1 year</time_frame>
    <description>Measurements of body weight in kilograms</description>
  </other_outcome>
  <other_outcome>
    <measure>Anthropometric measure 2</measure>
    <time_frame>1 year</time_frame>
    <description>Change in body fat percentage</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Depression</condition>
  <arm_group>
    <arm_group_label>depression participants - intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>personalized diet intervention based on microbiota analysis and health status</description>
  </arm_group>
  <arm_group>
    <arm_group_label>depression participants - control</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>General information on nutrition and health</description>
  </arm_group>
  <arm_group>
    <arm_group_label>pre-depression participants - control</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>General information on nutrition and health for pre-depression participants</description>
  </arm_group>
  <arm_group>
    <arm_group_label>pre-depression participants - intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>personalized diet intervention based on microbiota analysis and health status for pre-depression participants</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Personalized Diet-driven microbiota</intervention_name>
    <description>Based on the results of the individual microbiota profile, the investigators will formulate a specific diet aiming to enrich the distinct microbiota with organisms correlated to better mental health. The dietitian will visit each participant twice a month.</description>
    <arm_group_label>depression participants - intervention</arm_group_label>
    <arm_group_label>pre-depression participants - intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>General information on nutrition and health</intervention_name>
    <description>General information on nutrition and health. The dietitian will visit each participant twice a month.</description>
    <arm_group_label>depression participants - control</arm_group_label>
    <arm_group_label>pre-depression participants - control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects of both sexes aged 60 - 80, from northeastern Israel, Jewish, Druze and Arab&#xD;
             populations, will be recruited. Only healthy, independent people who agreed to take&#xD;
             part in the study and show depressive symptoms according to the Geriatrics Depression&#xD;
             Scale.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Elderly people with depression who are drug-treated or elderly who are nursing his/her&#xD;
             partner, and who are treated with antibiotics at least 4 weeks before taking fecal&#xD;
             samples.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ariella Ofran, M.D, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Clalit Health Services</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Snait Tamir, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Migal, Galilee Technology Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Shmuel Shamai, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shamir Research Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Adi Vitman- Schorr, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shamir Research Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Karen Jackson, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Migal, Galilee Technology Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ziv Mozes, M.Sc. RD</last_name>
    <phone>972503553800</phone>
    <email>zivo13@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Shamir Research Institute</name>
      <address>
        <city>Katzrin</city>
        <zip>1290000</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ziv Mozes, M.Sc. RD</last_name>
      <phone>972503553800</phone>
      <email>zivo13@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Adi Vitman- Schorr, Ph.D</last_name>
      <phone>972506301998</phone>
      <email>adivitman@gmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>August 12, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>October 21, 2020</last_update_submitted>
  <last_update_submitted_qc>October 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Personalized Diet</keyword>
  <keyword>Microbiota</keyword>
  <keyword>Depression</keyword>
  <keyword>Elderly</keyword>
  <keyword>Gut flora</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</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/NCT03256929
org study id: SHAMIRMB
nct id: NCT03256929
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The propose of the study is a multi-disciplinary project connecting nutritional and health
      sciences with social and behavioral sciences, and aimed at understanding the microbiota
      changes related to the third age and their effects on mood and mental health. The research
      aims are primarily practical: They will explore the influence of the gut flora on depression,
      which could help us to recommend diets that might reduce the risk of developing depression.
      The novelty of this proposal is in the design of personalized diet-driven microbiota
      alterations and health status to modulate depression in elderly. For the first time the
      improvement of mental health in the elderly will be studied through a nutritional and food
      habits approach based on microbiota changes upon ageing.
Depressive symptoms are highly prevalent in older populations, is one of the most serious
      public health problems faced by modern societies. The problems caused by depression, such as
      functional impairments, lead to decreased quality of life, poor recovery from illnesses and
      increased mortality in the elderly. Researchers have found that there are many possible
      connections between personal or physical variables and the risk of developing depression; it
      can be caused by sociodemographic factors, or cognitive and functional impairment,
      nutritional status is also related to development of depression.

      Recent studies have suggested that depressive symptoms are more prevalent in individuals with
      impaired nutritional status. The intestinal microbial population (microbiota), known
      influenced by several factors including nutrition, age, and stress.

      The microbiota is essential to human health, changes in composition microbiota play a role in
      metabolic, nutritional, physiological and immunological processes in the human body, recently
      reported also behavioral changes associated with anxiety and depression. The aging process is
      characterized by a decrease intestinal transit time, as a result of dental problems, decrease
      in saliva activity, and efficiency of digestion and absorption leading to changes in the
      microbiota composition, which causes an increase in sensitivity to the development of chronic
      and inflammatory diseases. Although other factors undoubtedly contribute to mental health
      decline in the elderly, the association of the intestinal microbiota of older people with
      inflammation, the clear association between diet and microbiota and the recent report on the
      correlation between changes in microbiota and depression have led us to hypothesize that diet
      can shape microbiota, which then affect mood status in older people and decreased depressive
      symptoms.

      The purpose of the study is to examine the effect of a custom diet based on the composition
      of the intestinal bacterial population (compared with a diet for a healthy lifestyle that is
      not based on a microbiotic profile), on moods and depression among the elderly.

      Before and after the intervention, several tests will be carried out, using stool sample for
      microbiota analysis, salivary cortisol measurement and clinical information (GDS, life style
      habits, CEBQ, FFQ), These measures will indicate participants' clinical, nutritional and
      mental situation before and after in order to probe the diet intervention impact on
      microbiota and its correlation to mental health.

      The infrastructure of this research includes several aspects - mood, health and nutrition
      status that are main parameters in life quality of the third age, and the research is based
      on the complementary cooperation of social and behavior sciences and nutrition and life
      sciences experts.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The first stage will be mapping all of the aged population of the research area, who will be interviewed (after receiving their consent) in order to determine those who are depressed. 200 depressed and pre-depression individuals (according to the GDS) will be chosen, and divided randomly into two groups- one will undergo the diet- driven microbiota adjustment personalized-intervention (nutrition advisory), and the other will get general information on nutrition and health .
primary purpose: Treatment
masking: Single (Participant)
measure: Mental health status - Depression
time frame: 1 year
description: Depression will be assessed using the Geriatric Depression Scale (GDS). changes in test score
measure: Microbiota profile
time frame: 1 year
description: Microbiota composition will be characterized from feces. The stool specimens will be collected and immediately put in buffer and stored at -20ºC for analysis and then will be kept at -80ºC in a locked freezer. The very low temperature is of significance to avoid variability in the stool bacterial composition and to preserve bacterial DNA in fecal samples. Total microbial DNA will be extracted using the PowerSoil DNA extraction kit (MoBio) and then submitted to 16S rRNA gene amplicon sequencing using paired end Illumina technology.
measure: Salivary Cortisol
time frame: 1 year
description: Salivary Cortisol Measurement - The sampling procedure is simple and non-invasive. The saliva sample will be collected by using the Salivettes and freezed as is. On the day of the assay, Salivette™ samples can be thawed and then centrifuged at low speed to separate the saliva sample from the gauze. The cortisol in saliva is remarkably stable and will be measured by the salivary cortisol kit.
measure: life style habits
time frame: 1 year
description: The life style habits questionnaire is based on MABAT ZAHAV, National Health and Nutrition Survey (Aged 60 and over) 2005-2006, Ministry of Health, Israel and includes demographic details, questions on health status, dental health, functional, cognitive and emotional states, use of medications and nutrition supplements, alcohol consumption, physical activity, smoking habits, eating and dieting patterns, nutritional knowledge and attitudes.
measure: Nutritional data collection - Food Frequency Questionnaire - FFQ
time frame: 1 year
description: Habitual dietary intake information that will be assessed using the Food Frequency Questionnaire (FFQ)
measure: Eating Behavior Questionnaire - CEBQ
time frame: 1 year
description: Appetite, gastrointestinal problems, and chewing and swallowing problems will be assessed using the Composite Eating Behavior Questionnaire (CEBQ)
measure: Anthropometric measure 1
time frame: 1 year
description: Measurements of body weight in kilograms
measure: Anthropometric measure 2
time frame: 1 year
description: Change in body fat percentage
arm group label: depression participants - intervention
arm group type: Experimental
description: personalized diet intervention based on microbiota analysis and health status
arm group label: depression participants - control
arm group type: Experimental
description: General information on nutrition and health
arm group label: pre-depression participants - control
arm group type: Experimental
description: General information on nutrition and health for pre-depression participants
arm group label: pre-depression participants - intervention
arm group type: Experimental
description: personalized diet intervention based on microbiota analysis and health status for pre-depression participants
intervention type: Behavioral
intervention name: Personalized Diet-driven microbiota
description: Based on the results of the individual microbiota profile, the investigators will formulate a specific diet aiming to enrich the distinct microbiota with organisms correlated to better mental health. The dietitian will visit each participant twice a month.
arm group label: depression participants - intervention
arm group label: pre-depression participants - intervention
intervention type: Behavioral
intervention name: General information on nutrition and health
description: General information on nutrition and health. The dietitian will visit each participant twice a month.
arm group label: depression participants - control
arm group label: pre-depression participants - control
criteria: 
gender: All
minimum age: 60 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ariella Ofran, M.D, MPH
role: Principal Investigator
affiliation: Clalit Health Services
last name: Snait Tamir, Prof.
role: Principal Investigator
affiliation: Migal, Galilee Technology Center
last name: Shmuel Shamai, Prof.
role: Principal Investigator
affiliation: Shamir Research Institute
last name: Adi Vitman- Schorr, Ph.D
role: Principal Investigator
affiliation: Shamir Research Institute
last name: Karen Jackson, Ph.D
role: Principal Investigator
affiliation: Migal, Galilee Technology Center
last name: Ziv Mozes, M.Sc. RD
phone: 972503553800
email: zivo13@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Israel
responsible party type: Sponsor
mesh term: Depression
sharing ipd: No