<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/NCT03273855</url>
  </required_header>
  <id_info>
    <org_study_id>2017/1655</org_study_id>
    <nct_id>NCT03273855</nct_id>
  </id_info>
  <brief_title>Randomized Controlled Trial of Fecal Microbiota Transplantation in Severe Obesity</brief_title>
  <acronym>RCTFMTOb</acronym>
  <official_title>Randomized Controlled Trial of Fecal Microbiota Transplantation in Severe Obesity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital of North Norway</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Norwegian University of Science and Technology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lovisenberg Diakonale Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nordlandssykehuset HF</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Helse Nord</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Tromso</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Norwegian University of Life Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Oslo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital of North Norway</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>
      This is a randomized, double-blinded and placebo controlled prospective trial with sixty&#xD;
      patients to investigate the effect of fecal microbiota transplantation (FMT) on body weight&#xD;
      in patients with severe obesity. We will also collect data that possibly could give a better&#xD;
      understanding of mechanisms of this correlation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Obesity is a main threat to public health in western countries. This condition increases the&#xD;
      risk of developing type 2 diabetes, cardiovascular diseases, physical stress disorders,&#xD;
      dispose for cancer and contributes to increased overall morbidity and mortality. However&#xD;
      sustained weight loss lead to the reduction of risk factors and improvement of several&#xD;
      obesity related co-morbidities.&#xD;
&#xD;
      Currently there are mainly two established treatments for severe obesity: a conservative&#xD;
      approach through lifestyle intervention and a surgical approach with bariatric surgery. The&#xD;
      gut microbiota is recognized as an environmental modulator of nutritional uptake and body&#xD;
      weight. This has led to the hypothesis that the gut microbiota could be a therapeutic target&#xD;
      fighting obesity. Fecal microbiota transplantation (FMT) has been applied for more than 50&#xD;
      years, and is a established treatment for refractory recurrent infection with Clostridium&#xD;
      Difficile (CDI). Recent scientific studies have also applied FMT as treatment for other&#xD;
      diseases like inflammatory bowel disease, irritable bowel disease and even metabolic syndrome&#xD;
      and the results are promising.&#xD;
&#xD;
      The sample size is determined based on data from the outpatient clinic at UNN Harstad medical&#xD;
      department. Patients here have an average weight loss of 2,5 % with conservative treatment.&#xD;
      This will therefore be the expected result in the control group (receiving placebo). A weight&#xD;
      reduction of 5-10% leads to significant improvement of health and quality of life, and a&#xD;
      weight change of this magnitude is therefore the hypothesis. The difference between the two&#xD;
      groups is estimated to 7,5 %. With these historical results, the sample size is estimated to&#xD;
      be 19 patients in each group. Extreme values will be eliminated; more than 3 SD out of the&#xD;
      average in the group. In this patient group, we must also be prepared to high degree loss of&#xD;
      follow-up near one third, which is also the experience from the clinic. We will include&#xD;
      totally 60 patients, 30 in each group.&#xD;
&#xD;
      The investigators are planning a randomized, double-blinded and placebo controlled&#xD;
      prospective trial with sixty patients to investigate the effect of fecal microbiota&#xD;
      transplantation (FMT) on body weight in patients with severe obesity. In the trial there will&#xD;
      also be collected data that possibly could give a better understanding of mechanisms of this&#xD;
      correlation; with insulin resistance, blood pressure, complete body scan, inflammation and&#xD;
      biochemical parameters of hepatic steatosis, changes in the patients microbiota and the&#xD;
      development in quality of life as secondary outcome measures.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">May 13, 2019</start_date>
  <completion_date type="Anticipated">May 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2023</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in individual weight loss (kg).</measure>
    <time_frame>Change from baseline body weight at 12 months post FMT</time_frame>
    <description>Partisipants will be measured at the outpatient clinic, medical department UNN Harstad, and weight in kilograms (kg) will be recorded. The data will be represented both as average weight change and as bar charts with &gt;10%, with comparison between the intervention and control group.&#xD;
Chi Square or Fischer exact test will be used to present responders and non-responders in the active and controll group. We will use odds ratio to present responders in the active group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in individual weight loss (kg)</measure>
    <time_frame>Change from baseline body weight at 3, 6 and 12 months after FMT</time_frame>
    <description>Partisipants will be measured at the outpatient clinic, medical department UNN Harstad, and weight in kilograms (kg) will be recorded. The data will be represented both as average weight change and as bar charts with &gt;5%, &gt;15% and &gt;20% weight loss, with comparison between the intervention and control group at each controll point.&#xD;
Chi Square or Fischer exact test will be used to present responders and non-responders in the active and controll group. We will use odds ratio to present responders in the active group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in waist circumference (cm)</measure>
    <time_frame>Change from baseline waist circumferense at 3, 6 and 12 months after FMT</time_frame>
    <description>Participants will be measured at the outpatient clinic, medical department UNN Harstad, and waist circumference (cm) will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in HbA1c (mmol/mol)</measure>
    <time_frame>Change from baseline HbA1c at 3, 6 and 12 months after FMT</time_frame>
    <description>Together with C-peptide, fasting glucose and insuline it will be used to research insuline resistance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in fasting glucose (mmol/L)</measure>
    <time_frame>Change from baseline fasting glucose at 3, 6 and 12 months after FMT</time_frame>
    <description>Together with HbA1c, C-peptide, and insuline it will be used to research insuline resistance and calculate HOMA-IR and HOMA-B</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in insuline (pmol/L)</measure>
    <time_frame>Change from baseline insuline at 3, 6 and 12 months after FMT</time_frame>
    <description>Together with HbA1c, C-peptide, and fasting glucose it will be used to research insuline resistance and calculate HOMA-IR and HOMA-B</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in C-peptide (pmol/L)</measure>
    <time_frame>Change from baseline C-peptide at 3, 6 and 12 months after FMT</time_frame>
    <description>Together with HbA1c, fasting glucose and insuline it will be used to research insuline resistance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in blood pressure</measure>
    <time_frame>Change from baseline blood pressure at 3, 6 and 12 months after FMT</time_frame>
    <description>Participants blood pressure (mmHg) will be measured at the outpatient clinic, medical department UNN Harstad. Blood pressure is collected as the average of the last two out of three measurements, at the end of 5 min resting period in supine position.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in sedimentation rate (mm/t)</measure>
    <time_frame>Change from baseline sedimentation rate at 3, 6 and 12 months after FMT</time_frame>
    <description>We will measure sedimentation rate, and together with hs-CRP and cytokine panel we will investigate inflamation between the group recieving placebo and the group recieving active transplant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in hs-CRP (mg/L)</measure>
    <time_frame>Change from baseline hs-CRP at 3, 6 and 12 months after FMT</time_frame>
    <description>We will measure hs-CRP, and together with sedimentation rate and cytokine panel we will investigate inflamation between the group recieving placebo and the group recieving active transplant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in multiplex cytokine panel (pg/mL)</measure>
    <time_frame>Change from baseline cytokine panel at 3, 6 and 12 months after FMT</time_frame>
    <description>We will run a multiplex cytokinepanel consiting of 27 different cytokines to see if the consentration of blood cytokines changes in participants after active treatment/placebo. The cytokine panel consists of TNF-a, IFN-g, IL-1b, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12(p70), IL-13, IL-15, IL-17A, MCP-1(MCAF), IP-10, Eotaxin, MIP-1a, MIP-1b, RANTES, G-CSF, GM-CSF, Basic FGF, PDGF-BB, VEGF.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in biochemical parameters of hepatic steatosis (U/L)</measure>
    <time_frame>Change from baseline biochemical parameters at 3, 6 and 12 months after FMT</time_frame>
    <description>Photometric analysis. We will measue AST, ALT, ALP, ɣGT and amylase to look at changes in biochemical parameters of hepatic steatosis between the group recieving placebo and the group recieving active transplant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in lipid profile based on HDL/LDL (mmol/L) and cholesterol (mmol/L)</measure>
    <time_frame>Change from baseline lipid profile at 3, 6 and 12 months afterFMT</time_frame>
    <description>Photometric analysis. Changes in cholesterol and HDL/LDL be used to look at changes in lipid profile between the group recieving placebo and the group recieving active transplant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in life quality measured using RAND-36 questionnaire</measure>
    <time_frame>Change from baseline RAND-36 score 12 months after FMT</time_frame>
    <description>RAND-36- Item Short Form Health Survey. The SF-36 consists of eight scaled scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning and mental health), which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. By an independent sample T-test (or, if necessary, non-parametric Mann-Whitney) we will compare change in global score. We will apply last value forward for missing values</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in psychiatric comorbidity measured by HSCL-25</measure>
    <time_frame>Change from baseline HSCL-25 score 12 months after FMT</time_frame>
    <description>HSCL-25. Consists of 25 questions. Each answer to a question has a value of 1-4. A total score over 1,75 points to psychological issues or impaired mental health</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in dietary intake measured by FFQ</measure>
    <time_frame>Change from baseline FFQ score at 3, 6 and 12 months after FMT</time_frame>
    <description>FFQ Change in dietary intakes measured using Food Frequency Questionnaire at baseline and at 3, 6 and 12 months after FMT will be examined.&#xD;
Energy measured as kcal, nutrition (gram) and different food groups reported as gram/day</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in life style measured by IPAQ</measure>
    <time_frame>Change from baseline IPAQ score at 3, 6 and 12 months after FMT</time_frame>
    <description>IPAQ Categorical Score&#xD;
Three levels (categories) of physical activity are proposed:&#xD;
Category 1: Low This is the lowest level of physical activity. Those individuals who not meet criteria for categories 2 or 3 are considered low/inactive.&#xD;
Category 2: Moderate&#xD;
Any one of the following 3 criteria:&#xD;
3 or more days of vigorous activity of at least 20 minutes per day OR&#xD;
5 or more days of moderate-intensity activity or walking of at least 30 minutes per day OR&#xD;
5 or more days of any combination of walking, moderate-intensity or vigorous intensity activities achieving a minimum of at least 600 MET-min/week.&#xD;
Category 3: High&#xD;
Any one of the following 2 criteria:&#xD;
Vigorous-intensity activity on at least 3 days and accumulating at least 1500 MET-minutes/ week OR&#xD;
7 or more days of any combination of walking, moderate-intensity or vigorous intensity activities achieving a minimum of at least 3000 MET-minutes/week</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gut microbiota composition and function</measure>
    <time_frame>Change from baseline microbiota composition at 3, 6 and 12 months after FMT</time_frame>
    <description>Microbiota analysis and SCFA in faeces</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short difficult childhood questionnaire</measure>
    <time_frame>At baseling</time_frame>
    <description>Questions of childhood trauma, four or six questions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Childhood trauma Questionnaire (CTQ)</measure>
    <time_frame>Once during the follow up period in the study</time_frame>
    <description>A validated questionnaire to collect self-reported data about adverse childhood experiences</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate variability (HRV)</measure>
    <time_frame>HRV will be measured at inclusion and 3.months post FMT</time_frame>
    <description>A dysbiotic gut microbiota that signals with the vagal nerve can cause an exaggerated stress response in obesity characterised by decrease in heart rate variability.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Engraftment of donor microbiota at 1, 3, 6 and 12 months.</measure>
    <time_frame>Inclusion, 2, 3, 6 and 12 months after FMT</time_frame>
    <description>Comparison between baseline profile, post FMT and donor profile will show if engraftment of donor microbiota parallels clinical response to active FMT.</description>
  </other_outcome>
  <other_outcome>
    <measure>Eating behaviour</measure>
    <time_frame>Change from baseline binge eating questionnaore score 12 months after FMT</time_frame>
    <description>Binge eating questionnaire</description>
  </other_outcome>
  <other_outcome>
    <measure>Questionnaire about the impact of covid-19 on life style changes and eating habits</measure>
    <time_frame>Once during the follow up period in the study</time_frame>
    <description>Participants which had undergone intervention and were in the follow up period, had all their appointments at the obesity clinic at UNN Harstad canceled, due to the covid-19 outbreak in the period march-20 to juli-20. This might have impacted their weight loss motivation and life style changes. We therefore asked them five questions, which we hope will shed light on the challenges they might encountered during the period of restrictions implemented by the Norwegian government.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Obesity, Morbid</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Active Comparator. Transplant from Donor A or Donor B, or Donor C or Donore D, one transplant consist of 50-80g of feacal matter.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo. Patient will recieve an autologous fecal microbiota transplantation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Fecal microbiota transplantation</intervention_name>
    <description>The intervention treatment is fecal microbiota transplantation made of frozen donor feces. The FMT is transferred as rectal enema where we use a rectal probe with a balloon to prevent leakage and keep the solution long enough in the colon. The patient will stay on the bench in different positions for 20 minutes. We will encourage the participant to keep the solution in the colon as long as possible and give them four pills of loperamide before the procedure in order to reduce bowel motility.</description>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo: fecal microbiota transplantation</intervention_name>
    <description>The placebo group get fecal microbiota transplantation made of their own feces. The FMT is transferred as rectal enema where we use a rectal probe with a balloon to prevent leakage and keep the solution long enough in the colon. The patient will stay on the bench in different positions for 20 minutes. We will encourage the participant to keep the solution in the colon as long as possible and give them four pills of loperamide before the procedure in order to reduce bowel motility.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  BMI &gt; 40 or BMI &gt; 35 kg/m2 combined with comorbidity related to obesity.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Symptomatic cardiovascular disease, lung disease, cirrhosis or significant renal&#xD;
             failure.&#xD;
&#xD;
          -  Patients who are pregnant or breastfeeding&#xD;
&#xD;
          -  Patients who have a confirmed malignancy or cancer&#xD;
&#xD;
          -  Patients who are immunocompromised&#xD;
&#xD;
          -  Previous gastric or small intestinal surgery that alters gut anatomy such as&#xD;
             fundoplication, gastric resection, gastric bypass, small bowel resection, and&#xD;
             ileoectomy&#xD;
&#xD;
          -  Established drug- or alcohol abuse or particularly unstable psychosocial&#xD;
             circumstances.&#xD;
&#xD;
          -  History of cholecystektomy (gut microbiota composition could be affected by bile acid&#xD;
             composition)&#xD;
&#xD;
          -  New drugs the last three months or during the follow-up period that can impact on&#xD;
             metabolism or body weight&#xD;
&#xD;
          -  Antibiotic treatment the last three months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>69 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Per C Valle, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital of North of Norway</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Maria S Fjellstad, cand.med</last_name>
    <role>Study Chair</role>
    <affiliation>University Hospital of North of Norway</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hege M Hanssen, M.Sc</last_name>
    <role>Study Chair</role>
    <affiliation>University Hospital of North Norway</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital of North Norway</name>
      <address>
        <city>Harstad</city>
        <state>Troms</state>
        <zip>9406</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>September 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 6, 2017</study_first_posted>
  <last_update_submitted>January 18, 2023</last_update_submitted>
  <last_update_submitted_qc>January 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</mesh_term>
    <mesh_term>Obesity, Morbid</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/NCT03273855
org study id: 2017/1655
nct id: NCT03273855
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a randomized, double-blinded and placebo controlled prospective trial with sixty
      patients to investigate the effect of fecal microbiota transplantation (FMT) on body weight
      in patients with severe obesity. We will also collect data that possibly could give a better
      understanding of mechanisms of this correlation.
Obesity is a main threat to public health in western countries. This condition increases the
      risk of developing type 2 diabetes, cardiovascular diseases, physical stress disorders,
      dispose for cancer and contributes to increased overall morbidity and mortality. However
      sustained weight loss lead to the reduction of risk factors and improvement of several
      obesity related co-morbidities.

      Currently there are mainly two established treatments for severe obesity: a conservative
      approach through lifestyle intervention and a surgical approach with bariatric surgery. The
      gut microbiota is recognized as an environmental modulator of nutritional uptake and body
      weight. This has led to the hypothesis that the gut microbiota could be a therapeutic target
      fighting obesity. Fecal microbiota transplantation (FMT) has been applied for more than 50
      years, and is a established treatment for refractory recurrent infection with Clostridium
      Difficile (CDI). Recent scientific studies have also applied FMT as treatment for other
      diseases like inflammatory bowel disease, irritable bowel disease and even metabolic syndrome
      and the results are promising.

      The sample size is determined based on data from the outpatient clinic at UNN Harstad medical
      department. Patients here have an average weight loss of 2,5 % with conservative treatment.
      This will therefore be the expected result in the control group (receiving placebo). A weight
      reduction of 5-10% leads to significant improvement of health and quality of life, and a
      weight change of this magnitude is therefore the hypothesis. The difference between the two
      groups is estimated to 7,5 %. With these historical results, the sample size is estimated to
      be 19 patients in each group. Extreme values will be eliminated; more than 3 SD out of the
      average in the group. In this patient group, we must also be prepared to high degree loss of
      follow-up near one third, which is also the experience from the clinic. We will include
      totally 60 patients, 30 in each group.

      The investigators are planning a randomized, double-blinded and placebo controlled
      prospective trial with sixty patients to investigate the effect of fecal microbiota
      transplantation (FMT) on body weight in patients with severe obesity. In the trial there will
      also be collected data that possibly could give a better understanding of mechanisms of this
      correlation; with insulin resistance, blood pressure, complete body scan, inflammation and
      biochemical parameters of hepatic steatosis, changes in the patients microbiota and the
      development in quality of life as secondary outcome measures.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double-blinded
measure: Change in individual weight loss (kg).
time frame: Change from baseline body weight at 12 months post FMT
description: Partisipants will be measured at the outpatient clinic, medical department UNN Harstad, and weight in kilograms (kg) will be recorded. The data will be represented both as average weight change and as bar charts with >10%, with comparison between the intervention and control group.
Chi Square or Fischer exact test will be used to present responders and non-responders in the active and controll group. We will use odds ratio to present responders in the active group.
measure: Change in individual weight loss (kg)
time frame: Change from baseline body weight at 3, 6 and 12 months after FMT
description: Partisipants will be measured at the outpatient clinic, medical department UNN Harstad, and weight in kilograms (kg) will be recorded. The data will be represented both as average weight change and as bar charts with >5%, >15% and >20% weight loss, with comparison between the intervention and control group at each controll point.
Chi Square or Fischer exact test will be used to present responders and non-responders in the active and controll group. We will use odds ratio to present responders in the active group.
measure: Change in waist circumference (cm)
time frame: Change from baseline waist circumferense at 3, 6 and 12 months after FMT
description: Participants will be measured at the outpatient clinic, medical department UNN Harstad, and waist circumference (cm) will be recorded.
measure: Changes in HbA1c (mmol/mol)
time frame: Change from baseline HbA1c at 3, 6 and 12 months after FMT
description: Together with C-peptide, fasting glucose and insuline it will be used to research insuline resistance.
measure: Changes in fasting glucose (mmol/L)
time frame: Change from baseline fasting glucose at 3, 6 and 12 months after FMT
description: Together with HbA1c, C-peptide, and insuline it will be used to research insuline resistance and calculate HOMA-IR and HOMA-B
measure: Changes in insuline (pmol/L)
time frame: Change from baseline insuline at 3, 6 and 12 months after FMT
description: Together with HbA1c, C-peptide, and fasting glucose it will be used to research insuline resistance and calculate HOMA-IR and HOMA-B
measure: Changes in C-peptide (pmol/L)
time frame: Change from baseline C-peptide at 3, 6 and 12 months after FMT
description: Together with HbA1c, fasting glucose and insuline it will be used to research insuline resistance.
measure: Change in blood pressure
time frame: Change from baseline blood pressure at 3, 6 and 12 months after FMT
description: Participants blood pressure (mmHg) will be measured at the outpatient clinic, medical department UNN Harstad. Blood pressure is collected as the average of the last two out of three measurements, at the end of 5 min resting period in supine position.
measure: Change in sedimentation rate (mm/t)
time frame: Change from baseline sedimentation rate at 3, 6 and 12 months after FMT
description: We will measure sedimentation rate, and together with hs-CRP and cytokine panel we will investigate inflamation between the group recieving placebo and the group recieving active transplant.
measure: Change in hs-CRP (mg/L)
time frame: Change from baseline hs-CRP at 3, 6 and 12 months after FMT
description: We will measure hs-CRP, and together with sedimentation rate and cytokine panel we will investigate inflamation between the group recieving placebo and the group recieving active transplant.
measure: Changes in multiplex cytokine panel (pg/mL)
time frame: Change from baseline cytokine panel at 3, 6 and 12 months after FMT
description: We will run a multiplex cytokinepanel consiting of 27 different cytokines to see if the consentration of blood cytokines changes in participants after active treatment/placebo. The cytokine panel consists of TNF-a, IFN-g, IL-1b, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12(p70), IL-13, IL-15, IL-17A, MCP-1(MCAF), IP-10, Eotaxin, MIP-1a, MIP-1b, RANTES, G-CSF, GM-CSF, Basic FGF, PDGF-BB, VEGF.
measure: Changes in biochemical parameters of hepatic steatosis (U/L)
time frame: Change from baseline biochemical parameters at 3, 6 and 12 months after FMT
description: Photometric analysis. We will measue AST, ALT, ALP, ɣGT and amylase to look at changes in biochemical parameters of hepatic steatosis between the group recieving placebo and the group recieving active transplant
measure: Changes in lipid profile based on HDL/LDL (mmol/L) and cholesterol (mmol/L)
time frame: Change from baseline lipid profile at 3, 6 and 12 months afterFMT
description: Photometric analysis. Changes in cholesterol and HDL/LDL be used to look at changes in lipid profile between the group recieving placebo and the group recieving active transplant
measure: Changes in life quality measured using RAND-36 questionnaire
time frame: Change from baseline RAND-36 score 12 months after FMT
description: RAND-36- Item Short Form Health Survey. The SF-36 consists of eight scaled scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning and mental health), which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. By an independent sample T-test (or, if necessary, non-parametric Mann-Whitney) we will compare change in global score. We will apply last value forward for missing values
measure: Changes in psychiatric comorbidity measured by HSCL-25
time frame: Change from baseline HSCL-25 score 12 months after FMT
description: HSCL-25. Consists of 25 questions. Each answer to a question has a value of 1-4. A total score over 1,75 points to psychological issues or impaired mental health
measure: Changes in dietary intake measured by FFQ
time frame: Change from baseline FFQ score at 3, 6 and 12 months after FMT
description: FFQ Change in dietary intakes measured using Food Frequency Questionnaire at baseline and at 3, 6 and 12 months after FMT will be examined.
Energy measured as kcal, nutrition (gram) and different food groups reported as gram/day
measure: Changes in life style measured by IPAQ
time frame: Change from baseline IPAQ score at 3, 6 and 12 months after FMT
description: IPAQ Categorical Score
Three levels (categories) of physical activity are proposed:
Category 1: Low This is the lowest level of physical activity. Those individuals who not meet criteria for categories 2 or 3 are considered low/inactive.
Category 2: Moderate
Any one of the following 3 criteria:
3 or more days of vigorous activity of at least 20 minutes per day OR
5 or more days of moderate-intensity activity or walking of at least 30 minutes per day OR
5 or more days of any combination of walking, moderate-intensity or vigorous intensity activities achieving a minimum of at least 600 MET-min/week.
Category 3: High
Any one of the following 2 criteria:
Vigorous-intensity activity on at least 3 days and accumulating at least 1500 MET-minutes/ week OR
7 or more days of any combination of walking, moderate-intensity or vigorous intensity activities achieving a minimum of at least 3000 MET-minutes/week
measure: Gut microbiota composition and function
time frame: Change from baseline microbiota composition at 3, 6 and 12 months after FMT
description: Microbiota analysis and SCFA in faeces
measure: Short difficult childhood questionnaire
time frame: At baseling
description: Questions of childhood trauma, four or six questions
measure: Childhood trauma Questionnaire (CTQ)
time frame: Once during the follow up period in the study
description: A validated questionnaire to collect self-reported data about adverse childhood experiences
measure: Heart rate variability (HRV)
time frame: HRV will be measured at inclusion and 3.months post FMT
description: A dysbiotic gut microbiota that signals with the vagal nerve can cause an exaggerated stress response in obesity characterised by decrease in heart rate variability.
measure: Engraftment of donor microbiota at 1, 3, 6 and 12 months.
time frame: Inclusion, 2, 3, 6 and 12 months after FMT
description: Comparison between baseline profile, post FMT and donor profile will show if engraftment of donor microbiota parallels clinical response to active FMT.
measure: Eating behaviour
time frame: Change from baseline binge eating questionnaore score 12 months after FMT
description: Binge eating questionnaire
measure: Questionnaire about the impact of covid-19 on life style changes and eating habits
time frame: Once during the follow up period in the study
description: Participants which had undergone intervention and were in the follow up period, had all their appointments at the obesity clinic at UNN Harstad canceled, due to the covid-19 outbreak in the period march-20 to juli-20. This might have impacted their weight loss motivation and life style changes. We therefore asked them five questions, which we hope will shed light on the challenges they might encountered during the period of restrictions implemented by the Norwegian government.
arm group label: Intervention
arm group type: Active Comparator
description: Active Comparator. Transplant from Donor A or Donor B, or Donor C or Donore D, one transplant consist of 50-80g of feacal matter.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo. Patient will recieve an autologous fecal microbiota transplantation.
intervention type: Other
intervention name: Fecal microbiota transplantation
description: The intervention treatment is fecal microbiota transplantation made of frozen donor feces. The FMT is transferred as rectal enema where we use a rectal probe with a balloon to prevent leakage and keep the solution long enough in the colon. The patient will stay on the bench in different positions for 20 minutes. We will encourage the participant to keep the solution in the colon as long as possible and give them four pills of loperamide before the procedure in order to reduce bowel motility.
arm group label: Intervention
intervention type: Other
intervention name: Placebo: fecal microbiota transplantation
description: The placebo group get fecal microbiota transplantation made of their own feces. The FMT is transferred as rectal enema where we use a rectal probe with a balloon to prevent leakage and keep the solution long enough in the colon. The patient will stay on the bench in different positions for 20 minutes. We will encourage the participant to keep the solution in the colon as long as possible and give them four pills of loperamide before the procedure in order to reduce bowel motility.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 69 Years
healthy volunteers: No
last name: Per C Valle, PhD
role: Principal Investigator
affiliation: University Hospital of North of Norway
last name: Maria S Fjellstad, cand.med
role: Study Chair
affiliation: University Hospital of North of Norway
last name: Hege M Hanssen, M.Sc
role: Study Chair
affiliation: University Hospital of North Norway
facility: 
country: Norway
responsible party type: Sponsor
mesh term: Obesity
mesh term: Obesity, Morbid
sharing ipd: No