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Fecal Microbiota Transplantation in Depression

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ClinicalTrials.gov Identifier: NCT03281044
Recruitment Status : Recruiting
First Posted : September 13, 2017
Last Update Posted : May 1, 2019
Sponsor:
Information provided by (Responsible Party):
André Schmidt, Psychiatric Hospital of the University of Basel

Tracking Information
First Submitted Date  ICMJE September 4, 2017
First Posted Date  ICMJE September 13, 2017
Last Update Posted Date May 1, 2019
Actual Study Start Date  ICMJE October 24, 2018
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 12, 2017)
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 ]
Efficacy measure
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03281044 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2017)
  • 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 ]
    Efficacy 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 ]
    Efficacy 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 ]
    Efficacy measure
  • Brain function (measured Blood-oxygen-level dependent contrast imaging) [ Time Frame: Change from baseline score to follow-up measurement after 1 month ]
    Efficacy measure
  • HPA axis function (measured with salivary cortisol awakening responses). [ Time Frame: Change from baseline score to follow-up measurement after 1 month ]
    Efficacy measure
  • Neurogenesis (measured with blood levels of BDNF). [ Time Frame: Change from baseline score to follow-up measurement after 1 month ]
    Efficacy 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 ]
    Efficacy 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 ]
    Efficacy measure
  • Cognition (measured with the Trail Making Test) [ Time Frame: Change from baseline score to follow-up measurement after 1 month ]
    Efficacy measure
  • Physical activity (measured with a portable wristwatch). [ Time Frame: Change from baseline score to follow-up measurement after 1 month ]
    Efficacy measure
  • Sleep quality (measured with 28-channel electroencephalography) [ Time Frame: Change from baseline score to follow-up measurement after 1 month ]
    Efficacy measure
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Fecal Microbiota Transplantation in Depression
Official Title  ICMJE Oral Frozen Fecal Microbiota Transplantation (FMT) Capsules for Depression: a Double-blind, Placebo-controlled, Randomized Parallel Group Study
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Major Depressive Disorder
Intervention  ICMJE
  • Drug: Fecal microbiota capsules
    Patients will receive FMP-402 capsules containing the fecal microbiota drug substance within a gelatin capsule shell. The drug substance is fecal microbiota from a single donor.
  • Drug: Placebo oral capsule
    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
Study Arms  ICMJE
  • Experimental: FMT group
    Patient group receiving active FMT capsules
    Intervention: Drug: Fecal microbiota capsules
  • Placebo Comparator: Placebo group
    Patient group receiving placebo capsules
    Intervention: Drug: Placebo oral capsule
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 12, 2017)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2021
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥ 18, body mass index 20-30 kg/m²
  • Able to provide signed and dated informed consent
  • Patients with moderate to severe depression (as expressed by a Hamilton Depression Rating Scale (HAMD-17) > 17)
  • Only treated with venlafaxine, serotonin reuptake inhibitors, seroquel and benzodiazepines
  • Medication should be stable for a month prior to enrolment
  • In-patient at the UPK Basel

Exclusion Criteria:

  • Patients with mild MDD (HAMD-17 < 17)
  • Comorbid psychiatric disturbances such as substance abuse disorder, bipolar disorder, schizophrenia, eating disorders.
  • Current medical conditions such as acute infectious disease,
  • Dietary restrictions (vegetarian, vegan, gluten-free, PEG/TPN feeding, and any kind of deviation from the UPK standard catering)
  • Recent use of medications besides their anti-depressant medication (within 3 months, mainly antibiotics or probiotic consumption within last six weeks).
  • Pregnancy (tested before both MRI scans using the AlereTM TestPack +Plus hCG Urine Test), breast-feeding
  • Body Mass Index (BMI) > 30
  • Current or recent use of antibiotics (within 3 months before inclusion)
  • Anticipated antibiotic use in upcoming 4 weeks
  • Inability to read and understand the participant's information and informed consent form
  • Inability (e.g. dysphagia) to or unwilling to swallow capsules
  • Active vomiting
  • Known or suspected toxic megacolon and/or known small bowel ileus
  • Major gastrointestinal surgery (e.g. significant bowel resection) within 3 months before enrolment. This does not include appendectomy or cholecystectomy.
  • History of total colectomy or bariatric surgery.
  • Concurrent intensive induction chemotherapy, radiation therapy or biological treatment for active malignancy. Patients on maintenance chemotherapy may be enrolled only after consultation with a medical monitor.
  • Life expectancy < 6 months
  • Patients with a history of severe anaphylactic or anaphylactoid food allergy
  • Solid organ transplant recipients ≤ 90 days post-transplant or on active treatment for rejection
  • Neuropenia (≤500 neutrophils/mL) or other severe immunosuppression. Anti-TNF will be permitted. Patients on monoclonal antibodies to B and T cells, glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine, methotrexate), calcineurin inhbitors (tacrolimus, cyclosporine) and mycophenolate mofetil may be enrolled only after consultation with the medical monitor.
  • A condition that would jeopardize the safety or rights of the subject, would make it unlikely for the subject to complete the study, or would confound the results of the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: André Schmidt 613255929 andre.schmidt@unibas.ch
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03281044
Other Study ID Numbers  ICMJE 2017-01050
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party André Schmidt, Psychiatric Hospital of the University of Basel
Study Sponsor  ICMJE Psychiatric Hospital of the University of Basel
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: André Schmidt University of Basel, Department of Psychiatry (UPK)
PRS Account Psychiatric Hospital of the University of Basel
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP