<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/NCT04453150</url>
  </required_header>
  <id_info>
    <org_study_id>ISCIII CP18/01160</org_study_id>
    <nct_id>NCT04453150</nct_id>
  </id_info>
  <brief_title>Microbiota in Dietary Approach to Obesity</brief_title>
  <official_title>Ketone Bodies and Gut Microbiota Role in the Dietetic Approach of Obesity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud</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>
      Main aim: Study the anthropometric, metabolic, cardiovascular and neurocognitive and gut&#xD;
      microbiota changes of different approaches for the weight reduction that increase the ketone&#xD;
      bodies in a different proportion in relation to the classic hypocaloric diet.&#xD;
&#xD;
      Objective 1: Study the effect of hypocaloric diets that increase the ketone bodies on gut&#xD;
      microbiota and its relationship with anthropometric changes and of the Brown adipose tissue,&#xD;
      Objective 2: with the metabolic and inflammatory changes, Objective 3: on the cardiovascular&#xD;
      system, Objective 4: on the neurocognition, Objective 5: if they are associated to epigenetic&#xD;
      changes that may explain the changes found in the other objectives. Objective 6: Determine&#xD;
      the safety of the diets that increase the ketone bodies compared to the classic hypocaloric&#xD;
      diet, Objective 7: if the effects of the different dietary approaches are maintained during&#xD;
      the medium time, and Objective 8: Verify in experimental models (microbiota transplants from&#xD;
      humans with different diets to germ-free mice, ketosis dietary models, and ketone bodies&#xD;
      administration) the causality of the gut microbiota of these findings.&#xD;
&#xD;
      Methodology: Model 1: Dietary intervention in humans with 4 types of diet with a different&#xD;
      increase of the ketone bodies: classic hypocaloric diet (DH); diet with 8h of feeding and 16h&#xD;
      of starving in periods of 24h (D16); diet with intermittent caloric restriction (DA); and&#xD;
      normal in protein and low in carbohydrates hypocaloric ketogenic diet (DC).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 22, 2020</start_date>
  <completion_date type="Actual">June 22, 2022</completion_date>
  <primary_completion_date type="Actual">June 9, 2022</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in gut microbiota composition</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>To evaluate changes in gut microbiota composition from baseline using different strategies for weight loss which increase ketone bodies in comparison to a standard hypocaloric diet. Change from baseline in 16S rRNA amplicons of fecal community DNA at 3 months and 6 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in weight</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>To analyze the effect of hypocaloric diets which increase ketone bodies on anthropometric parameters in comparison to a standard hypocaloric diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in body mass index.</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>To analyze the effect of hypocaloric diets which increase ketone bodies on body mass index in comparison to a standard hypocaloric diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in waist circumference.</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>To analyze the effect of hypocaloric diets which increase ketone bodies on the waist circumference in comparison to a standard hypocaloric diet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in body composition.</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>To analyze the effect of hypocaloric diets which increase ketone bodies on anthropometric parameters in comparison to a standard hypocaloric diet measured by bioelectrical impedance analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in brown adipose tissue.</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>To analyze the effect of hypocaloric diets which increase ketone bodies on brown adipose tissue in comparison to a standard hypocaloric diet, measured by Positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG PET).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in uncoupling protein 1 (UCP1)</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>To analyze the effect of hypocaloric diets which increase ketone bodies on brown adipose tissue UCP1 in comparison to a standard hypocaloric diet using a sample of subcutaneous white adipose tissue assessed by mRNA qPCR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in physical activity.</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>To analyze the effect of hypocaloric diets which increase ketone bodies on physical activity in comparison to a standard hypocaloric diet measured by accelerometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in blood pressure</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>To analyze the effect of hypocaloric diets which increase ketone bodies over the cardiovascular system in comparison to a standard hypocaloric diet based on blood pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the punctuation in neurocognitive test</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>To analyze the effect of hypocaloric diets which increase ketone bodies on neurocognition, in comparison to a standard hypocaloric diet, measured by neurocognitive test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in heart rate</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>To analyze the effect of hypocaloric diets which increase ketone bodies on heart function measured by heart rate in comparison to a standard hypocaloric diet, measured by Holter.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Standard hypocaloric diet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mediterranean diet based on olive oil as main fat and regular consumption of vegetables (2 daily rations), fruits 3 daily rations), legumes (3 weekly rations), fish (3 weekly rations), with low consumption of red meat and meat products (less than twice a week), dairy foods (less than once a week) and no sweets, pastries or sugary drinks. Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein distributed in at least 4 meals (breakfast, lunch, afternoon snack and dinner).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intermittent fasting 16/8 (early fasting)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein, but it will be consumed for 8 hours a day (from 12 am. to 8 pm.), maintaining 16 fasting hours (from 8 pm. to 12 am. the following day).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intermittent fasting 16/8 (late fasting)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein, but it will be consumed for 8 hours a day (from 8 am. to 4 pm.), maintaining 16 fasting hours (from 4 pm. to 8 am. the following day).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Alternate-day fasting</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this diet subjects alternate norm caloric diet during 24 h (according to Harris-Benedict equation) and a diet including only 25% of caloric requirements the following 24 h (this day diet will include 5 % carbohydrates, 65% fat and 30% high biological value protein).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ketogenic diet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 5 % carbohydrates, 65% fat and 30% high biological value protein.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard hypocaloric die</intervention_name>
    <description>Standard hypocaloric diet</description>
    <arm_group_label>Standard hypocaloric diet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Intermittent fasting 16/8 (early fasting)</intervention_name>
    <description>Intermittent fasting 16/8 (early fasting)</description>
    <arm_group_label>Intermittent fasting 16/8 (early fasting)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Intermittent fasting 16/8 (late fasting)</intervention_name>
    <description>Intermittent fasting 16/8 (late fasting)</description>
    <arm_group_label>Intermittent fasting 16/8 (late fasting)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Alternate-day fasting</intervention_name>
    <description>Alternate-day fasting</description>
    <arm_group_label>Alternate-day fasting</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ketogenic diet</intervention_name>
    <description>Ketogenic diet</description>
    <arm_group_label>Ketogenic diet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Obesity (BMI≥30-45 kg/m2)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Type 2 diabetes mellitus&#xD;
&#xD;
          -  Patients with major cardiovascular events in the 6 months prior to the study&#xD;
             beginning.&#xD;
&#xD;
          -  Previous or current history of inflammatory disease.&#xD;
&#xD;
          -  Active infectious disease.&#xD;
&#xD;
          -  The refusal of the patient to participate in the study&#xD;
&#xD;
          -  Consumption of probiotics or prebiotics&#xD;
&#xD;
          -  Antibiotic therapy in the 3 months prior to the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Francisco J. Tinahones, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instituto de Investigacion Biomedica de Malaga</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Virgen de la Victoria Hospital</name>
      <address>
        <city>Malaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>April 17, 2020</study_first_submitted>
  <study_first_submitted_qc>June 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>July 5, 2022</last_update_submitted>
  <last_update_submitted_qc>July 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ketosis</keyword>
  <keyword>Microbiota</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</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/NCT04453150
org study id: ISCIII CP18/01160
nct id: NCT04453150
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Main aim: Study the anthropometric, metabolic, cardiovascular and neurocognitive and gut
      microbiota changes of different approaches for the weight reduction that increase the ketone
      bodies in a different proportion in relation to the classic hypocaloric diet.

      Objective 1: Study the effect of hypocaloric diets that increase the ketone bodies on gut
      microbiota and its relationship with anthropometric changes and of the Brown adipose tissue,
      Objective 2: with the metabolic and inflammatory changes, Objective 3: on the cardiovascular
      system, Objective 4: on the neurocognition, Objective 5: if they are associated to epigenetic
      changes that may explain the changes found in the other objectives. Objective 6: Determine
      the safety of the diets that increase the ketone bodies compared to the classic hypocaloric
      diet, Objective 7: if the effects of the different dietary approaches are maintained during
      the medium time, and Objective 8: Verify in experimental models (microbiota transplants from
      humans with different diets to germ-free mice, ketosis dietary models, and ketone bodies
      administration) the causality of the gut microbiota of these findings.

      Methodology: Model 1: Dietary intervention in humans with 4 types of diet with a different
      increase of the ketone bodies: classic hypocaloric diet (DH); diet with 8h of feeding and 16h
      of starving in periods of 24h (D16); diet with intermittent caloric restriction (DA); and
      normal in protein and low in carbohydrates hypocaloric ketogenic diet (DC).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Changes in gut microbiota composition
time frame: Baseline, 12 weeks
description: To evaluate changes in gut microbiota composition from baseline using different strategies for weight loss which increase ketone bodies in comparison to a standard hypocaloric diet. Change from baseline in 16S rRNA amplicons of fecal community DNA at 3 months and 6 months
measure: Changes in weight
time frame: Baseline, 12 weeks
description: To analyze the effect of hypocaloric diets which increase ketone bodies on anthropometric parameters in comparison to a standard hypocaloric diet
measure: Changes in body mass index.
time frame: Baseline, 12 weeks
description: To analyze the effect of hypocaloric diets which increase ketone bodies on body mass index in comparison to a standard hypocaloric diet
measure: Changes in waist circumference.
time frame: Baseline, 12 weeks
description: To analyze the effect of hypocaloric diets which increase ketone bodies on the waist circumference in comparison to a standard hypocaloric diet
measure: Changes in body composition.
time frame: Baseline, 12 weeks
description: To analyze the effect of hypocaloric diets which increase ketone bodies on anthropometric parameters in comparison to a standard hypocaloric diet measured by bioelectrical impedance analysis
measure: Changes in brown adipose tissue.
time frame: Baseline, 12 weeks
description: To analyze the effect of hypocaloric diets which increase ketone bodies on brown adipose tissue in comparison to a standard hypocaloric diet, measured by Positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG PET).
measure: Changes in uncoupling protein 1 (UCP1)
time frame: Baseline, 12 weeks
description: To analyze the effect of hypocaloric diets which increase ketone bodies on brown adipose tissue UCP1 in comparison to a standard hypocaloric diet using a sample of subcutaneous white adipose tissue assessed by mRNA qPCR.
measure: Changes in physical activity.
time frame: Baseline, 12 weeks
description: To analyze the effect of hypocaloric diets which increase ketone bodies on physical activity in comparison to a standard hypocaloric diet measured by accelerometry
measure: Changes in blood pressure
time frame: Baseline, 12 weeks
description: To analyze the effect of hypocaloric diets which increase ketone bodies over the cardiovascular system in comparison to a standard hypocaloric diet based on blood pressure
measure: Changes in the punctuation in neurocognitive test
time frame: Baseline, 12 weeks
description: To analyze the effect of hypocaloric diets which increase ketone bodies on neurocognition, in comparison to a standard hypocaloric diet, measured by neurocognitive test
measure: Changes in heart rate
time frame: Baseline, 12 weeks
description: To analyze the effect of hypocaloric diets which increase ketone bodies on heart function measured by heart rate in comparison to a standard hypocaloric diet, measured by Holter.
arm group label: Standard hypocaloric diet
arm group type: Experimental
description: Mediterranean diet based on olive oil as main fat and regular consumption of vegetables (2 daily rations), fruits 3 daily rations), legumes (3 weekly rations), fish (3 weekly rations), with low consumption of red meat and meat products (less than twice a week), dairy foods (less than once a week) and no sweets, pastries or sugary drinks. Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein distributed in at least 4 meals (breakfast, lunch, afternoon snack and dinner).
arm group label: Intermittent fasting 16/8 (early fasting)
arm group type: Experimental
description: Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein, but it will be consumed for 8 hours a day (from 12 am. to 8 pm.), maintaining 16 fasting hours (from 8 pm. to 12 am. the following day).
arm group label: Intermittent fasting 16/8 (late fasting)
arm group type: Experimental
description: Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein, but it will be consumed for 8 hours a day (from 8 am. to 4 pm.), maintaining 16 fasting hours (from 4 pm. to 8 am. the following day).
arm group label: Alternate-day fasting
arm group type: Experimental
description: In this diet subjects alternate norm caloric diet during 24 h (according to Harris-Benedict equation) and a diet including only 25% of caloric requirements the following 24 h (this day diet will include 5 % carbohydrates, 65% fat and 30% high biological value protein).
arm group label: Ketogenic diet
arm group type: Experimental
description: Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 5 % carbohydrates, 65% fat and 30% high biological value protein.
intervention type: Other
intervention name: Standard hypocaloric die
description: Standard hypocaloric diet
arm group label: Standard hypocaloric diet
intervention type: Other
intervention name: Intermittent fasting 16/8 (early fasting)
description: Intermittent fasting 16/8 (early fasting)
arm group label: Intermittent fasting 16/8 (early fasting)
intervention type: Other
intervention name: Intermittent fasting 16/8 (late fasting)
description: Intermittent fasting 16/8 (late fasting)
arm group label: Intermittent fasting 16/8 (late fasting)
intervention type: Other
intervention name: Alternate-day fasting
description: Alternate-day fasting
arm group label: Alternate-day fasting
intervention type: Other
intervention name: Ketogenic diet
description: Ketogenic diet
arm group label: Ketogenic diet
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Francisco J. Tinahones, PhD
role: Principal Investigator
affiliation: Instituto de Investigacion Biomedica de Malaga
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Obesity