<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/NCT03281044</url>
  </required_header>
  <id_info>
    <org_study_id>2017-01050</org_study_id>
    <nct_id>NCT03281044</nct_id>
  </id_info>
  <brief_title>Fecal Microbiota Transplantation in Depression</brief_title>
  <official_title>Oral Frozen Fecal Microbiota Transplantation (FMT) Capsules for Depression: a Double-blind, Placebo-controlled, Randomized Parallel Group Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Psychiatric Hospital of the University of Basel</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Psychiatric Hospital of the University of Basel</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 prevalence of psychiatric disorders such as major depression disorder (MDD) is increasing&#xD;
      rapidly. Despite advancements in the development of therapeutics, current treatment options&#xD;
      have not reached optimal efficacy.&#xD;
&#xD;
      Recent interest has been drawn towards the importance of the biochemical signalling between&#xD;
      the gastrointestinal tract and the central nervous system also known as the&#xD;
      &quot;microbiome-gut-brain axis&quot;. The pathogenesis of gut microbiota in extra intestinal diseases&#xD;
      was inspired by massive studies in germ free (GF) animals, which indicated that the gut&#xD;
      microbiota plays a role in the normal regulation of behaviour that are relevant to mood,&#xD;
      anxiety and stress. However, the exact mechanisms by which intestinal dysbiosis are involved&#xD;
      in the development of psychiatric diseases are not completely clarified.&#xD;
&#xD;
      A new method to alter the composition of the gastrointestinal microbiota involves fecal&#xD;
      microbiota transplantation (FMT). The goal of FMT is to introduce or restore a stable&#xD;
      microbial community in the gut by transplanting intestinal microbiota from a healthy donor to&#xD;
      the patient. FMT, as a microbiota-target therapy, is arguably very effective for curing&#xD;
      recurrent Clostridium difficile infection and has good outcomes in other intestinal diseases.&#xD;
      At the same time, applications in previously unexpected areas, including metabolic diseases,&#xD;
      neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors have shown&#xD;
      health enhancing results. FMT has initially been conducted using colonoscopy. However, recent&#xD;
      evidence has shown that treatment with frozen FMT capsules (to be taken orally) is also safe&#xD;
      and beneficial in restoring the gut microbiota in patients with various diseases As FMT&#xD;
      capsules may be an effective, pragmatical adjuvant therapy (in addition to standard&#xD;
      treatment) for depression, this project is aimed at (1) investigating for the first time if&#xD;
      single administration of FMT capsules ameliorates depressive symptoms in patients with&#xD;
      moderate to severe MDD 4 weeks after treatment and (2) establishing the safety profile of&#xD;
      encapsulated FMT in MDD. Furthermore, we will also test if (3) FMT capsules modulates immune&#xD;
      signalling and inflammatory processes, (4) Hypothalamic-pituitary-adrenal (HPA) axis&#xD;
      responses, (5) neurogenesis, (6) energy balance hormones, (7) gut microbiota composition and&#xD;
      (8) brain perfusion, structure and activation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Although not observed in our patients (4 enrolled), SAEs have been reported in other patients&#xD;
    receiving the same product.&#xD;
  </why_stopped>
  <start_date type="Actual">October 24, 2018</start_date>
  <completion_date type="Actual">March 16, 2020</completion_date>
  <primary_completion_date type="Actual">March 16, 2020</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Depressive symptoms as measured with the Hamilton Rating Scale for Depression</measure>
    <time_frame>Change from baseline score to follow-up measurements at 1, 2 and 8 months</time_frame>
    <description>Efficacy measure</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Gut microbiota composition as assessed by 16-S-rRNA sequencing of stool samples</measure>
    <time_frame>Change from baseline score to follow-up measurement after 1 month</time_frame>
    <description>Efficacy measure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cerebral blood flow (measured with arterial spin labeling, mL/100 g/min^10)</measure>
    <time_frame>Change from baseline score to follow-up measurement after 1 month</time_frame>
    <description>Efficacy measure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain structure (measured with structural magnetic resonance imaging to assess gray matter volume in mm^3, and diffusion tensor imaging to assess fractional anisotropy (dimensionless) and mean diffusivity (m2/s))</measure>
    <time_frame>Change from baseline score to follow-up measurement after 1 month</time_frame>
    <description>Efficacy measure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain function (measured Blood-oxygen-level dependent contrast imaging)</measure>
    <time_frame>Change from baseline score to follow-up measurement after 1 month</time_frame>
    <description>Efficacy measure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HPA axis function (measured with salivary cortisol awakening responses).</measure>
    <time_frame>Change from baseline score to follow-up measurement after 1 month</time_frame>
    <description>Efficacy measure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurogenesis (measured with blood levels of BDNF).</measure>
    <time_frame>Change from baseline score to follow-up measurement after 1 month</time_frame>
    <description>Efficacy measure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Appetite-regulating hormones (measured with blood levels of ghrelin and leptin).</measure>
    <time_frame>Change from baseline score to follow-up measurement after 1 month</time_frame>
    <description>Efficacy measure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunoregulation and inflammation (measured with blood levels of macrophage migration inhibitory factor and interleukin 1 beta).</measure>
    <time_frame>Change from baseline score to follow-up measurement after 1 month</time_frame>
    <description>Efficacy measure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognition (measured with the Trail Making Test)</measure>
    <time_frame>Change from baseline score to follow-up measurement after 1 month</time_frame>
    <description>Efficacy measure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical activity (measured with a portable wristwatch).</measure>
    <time_frame>Change from baseline score to follow-up measurement after 1 month</time_frame>
    <description>Efficacy measure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep quality (measured with 28-channel electroencephalography)</measure>
    <time_frame>Change from baseline score to follow-up measurement after 1 month</time_frame>
    <description>Efficacy measure</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>FMT group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient group receiving active FMT capsules</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patient group receiving placebo capsules</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fecal microbiota capsules</intervention_name>
    <description>Patients will receive FMT capsules DE containing the fecal microbiota drug substance within a gelatin capsule shell. The drug substance is fecal microbiota from a single donor.</description>
    <arm_group_label>FMT group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>The control condition is a placebo FMT capsule. The FMT placebo capsule is identical in appearance to active capsules, but does not contain human feces, the active pharmaceutical ingredient. Placebo capsules will contain an autoclaved solution of glycerol and saline, contained in an identical gelatin capsule as the active product, including the same enteric polymer coating</description>
    <arm_group_label>Placebo group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18, body mass index 20-30 kg/m²&#xD;
&#xD;
          -  Able to provide signed and dated informed consent&#xD;
&#xD;
          -  Patients with moderate to severe depression (as expressed by a Hamilton Depression&#xD;
             Rating Scale (HAMD-17) &gt; 17)&#xD;
&#xD;
          -  Treatment as usual for depression&#xD;
&#xD;
          -  In- and outpatients at the UPK Basel&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with mild MDD (HAMD-17 &lt; 17)&#xD;
&#xD;
          -  Comorbid psychiatric disturbances such as substance abuse disorder, bipolar disorder,&#xD;
             schizophrenia, eating disorders.&#xD;
&#xD;
          -  Current medical conditions such as acute infectious disease,&#xD;
&#xD;
          -  Dietary restrictions (vegetarian, vegan, gluten-free, PEG/TPN feeding, and any kind of&#xD;
             deviation from the UPK standard catering)&#xD;
&#xD;
          -  Recent use of medications besides their anti-depressant medication (within 3 months,&#xD;
             mainly antibiotics or probiotic consumption within last six weeks).&#xD;
&#xD;
          -  Pregnancy (tested before both MRI scans using the AlereTM TestPack +Plus hCG Urine&#xD;
             Test), breast-feeding&#xD;
&#xD;
          -  Body Mass Index (BMI) &gt; 30&#xD;
&#xD;
          -  Current or recent use of antibiotics (within 3 months before inclusion)&#xD;
&#xD;
          -  Anticipated antibiotic use in upcoming 4 weeks&#xD;
&#xD;
          -  Inability to read and understand the participant's information and informed consent&#xD;
             form&#xD;
&#xD;
          -  Inability (e.g. dysphagia) to or unwilling to swallow capsules&#xD;
&#xD;
          -  Active vomiting&#xD;
&#xD;
          -  Known or suspected toxic megacolon and/or known small bowel ileus&#xD;
&#xD;
          -  Major gastrointestinal surgery (e.g. significant bowel resection) within 3 months&#xD;
             before enrolment. This does not include appendectomy or cholecystectomy.&#xD;
&#xD;
          -  History of total colectomy or bariatric surgery.&#xD;
&#xD;
          -  Concurrent intensive induction chemotherapy, radiation therapy or biological treatment&#xD;
             for active malignancy. Patients on maintenance chemotherapy may be enrolled only after&#xD;
             consultation with a medical monitor.&#xD;
&#xD;
          -  Life expectancy &lt; 6 months&#xD;
&#xD;
          -  Patients with a history of severe anaphylactic or anaphylactoid food allergy&#xD;
&#xD;
          -  Solid organ transplant recipients ≤ 90 days post-transplant or on active treatment for&#xD;
             rejection&#xD;
&#xD;
          -  Neuropenia (≤500 neutrophils/mL) or other severe immunosuppression. Anti-TNF will be&#xD;
             permitted. Patients on monoclonal antibodies to B and T cells, glucocorticoids,&#xD;
             antimetabolites (azathioprine, 6-mercaptopurine, methotrexate), calcineurin inhbitors&#xD;
             (tacrolimus, cyclosporine) and mycophenolate mofetil may be enrolled only after&#xD;
             consultation with the medical monitor.&#xD;
&#xD;
          -  A condition that would jeopardize the safety or rights of the subject, would make it&#xD;
             unlikely for the subject to complete the study, or would confound the results of the&#xD;
             study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>André Schmidt</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Basel, Department of Psychiatry (UPK)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Psychiatric Clinics (UPK)</name>
      <address>
        <city>Basel</city>
        <zip>4012</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>September 4, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <last_update_submitted>April 15, 2020</last_update_submitted>
  <last_update_submitted_qc>April 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Psychiatric Hospital of the University of Basel</investigator_affiliation>
    <investigator_full_name>André Schmidt</investigator_full_name>
    <investigator_title>Research Group Leader</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03281044
org study id: 2017-01050
nct id: NCT03281044
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The prevalence of psychiatric disorders such as major depression disorder (MDD) is increasing
      rapidly. Despite advancements in the development of therapeutics, current treatment options
      have not reached optimal efficacy.

      Recent interest has been drawn towards the importance of the biochemical signalling between
      the gastrointestinal tract and the central nervous system also known as the
      "microbiome-gut-brain axis". The pathogenesis of gut microbiota in extra intestinal diseases
      was inspired by massive studies in germ free (GF) animals, which indicated that the gut
      microbiota plays a role in the normal regulation of behaviour that are relevant to mood,
      anxiety and stress. However, the exact mechanisms by which intestinal dysbiosis are involved
      in the development of psychiatric diseases are not completely clarified.

      A new method to alter the composition of the gastrointestinal microbiota involves fecal
      microbiota transplantation (FMT). The goal of FMT is to introduce or restore a stable
      microbial community in the gut by transplanting intestinal microbiota from a healthy donor to
      the patient. FMT, as a microbiota-target therapy, is arguably very effective for curing
      recurrent Clostridium difficile infection and has good outcomes in other intestinal diseases.
      At the same time, applications in previously unexpected areas, including metabolic diseases,
      neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors have shown
      health enhancing results. FMT has initially been conducted using colonoscopy. However, recent
      evidence has shown that treatment with frozen FMT capsules (to be taken orally) is also safe
      and beneficial in restoring the gut microbiota in patients with various diseases As FMT
      capsules may be an effective, pragmatical adjuvant therapy (in addition to standard
      treatment) for depression, this project is aimed at (1) investigating for the first time if
      single administration of FMT capsules ameliorates depressive symptoms in patients with
      moderate to severe MDD 4 weeks after treatment and (2) establishing the safety profile of
      encapsulated FMT in MDD. Furthermore, we will also test if (3) FMT capsules modulates immune
      signalling and inflammatory processes, (4) Hypothalamic-pituitary-adrenal (HPA) axis
      responses, (5) neurogenesis, (6) energy balance hormones, (7) gut microbiota composition and
      (8) brain perfusion, structure and activation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Depressive symptoms as measured with the Hamilton Rating Scale for Depression
time frame: Change from baseline score to follow-up measurements at 1, 2 and 8 months
description: Efficacy measure
measure: Gut microbiota composition as assessed by 16-S-rRNA sequencing of stool samples
time frame: Change from baseline score to follow-up measurement after 1 month
description: Efficacy measure
measure: Cerebral blood flow (measured with arterial spin labeling, mL/100 g/min^10)
time frame: Change from baseline score to follow-up measurement after 1 month
description: Efficacy measure
measure: Brain structure (measured with structural magnetic resonance imaging to assess gray matter volume in mm^3, and diffusion tensor imaging to assess fractional anisotropy (dimensionless) and mean diffusivity (m2/s))
time frame: Change from baseline score to follow-up measurement after 1 month
description: Efficacy measure
measure: Brain function (measured Blood-oxygen-level dependent contrast imaging)
time frame: Change from baseline score to follow-up measurement after 1 month
description: Efficacy measure
measure: HPA axis function (measured with salivary cortisol awakening responses).
time frame: Change from baseline score to follow-up measurement after 1 month
description: Efficacy measure
measure: Neurogenesis (measured with blood levels of BDNF).
time frame: Change from baseline score to follow-up measurement after 1 month
description: Efficacy measure
measure: Appetite-regulating hormones (measured with blood levels of ghrelin and leptin).
time frame: Change from baseline score to follow-up measurement after 1 month
description: Efficacy measure
measure: Immunoregulation and inflammation (measured with blood levels of macrophage migration inhibitory factor and interleukin 1 beta).
time frame: Change from baseline score to follow-up measurement after 1 month
description: Efficacy measure
measure: Cognition (measured with the Trail Making Test)
time frame: Change from baseline score to follow-up measurement after 1 month
description: Efficacy measure
measure: Physical activity (measured with a portable wristwatch).
time frame: Change from baseline score to follow-up measurement after 1 month
description: Efficacy measure
measure: Sleep quality (measured with 28-channel electroencephalography)
time frame: Change from baseline score to follow-up measurement after 1 month
description: Efficacy measure
arm group label: FMT group
arm group type: Experimental
description: Patient group receiving active FMT capsules
arm group label: Placebo group
arm group type: Placebo Comparator
description: Patient group receiving placebo capsules
intervention type: Drug
intervention name: Fecal microbiota capsules
description: Patients will receive FMT capsules DE containing the fecal microbiota drug substance within a gelatin capsule shell. The drug substance is fecal microbiota from a single donor.
arm group label: FMT group
intervention type: Drug
intervention name: Placebo oral capsule
description: The control condition is a placebo FMT capsule. The FMT placebo capsule is identical in appearance to active capsules, but does not contain human feces, the active pharmaceutical ingredient. Placebo capsules will contain an autoclaved solution of glycerol and saline, contained in an identical gelatin capsule as the active product, including the same enteric polymer coating
arm group label: Placebo group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: André Schmidt
role: Principal Investigator
affiliation: University of Basel, Department of Psychiatry (UPK)
facility: 
country: Switzerland
responsible party type: Principal Investigator
investigator affiliation: Psychiatric Hospital of the University of Basel
investigator full name: André Schmidt
investigator title: Research Group Leader
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
sharing ipd: Undecided