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Fecal Microbiota Transplantation in Depression

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ClinicalTrials.gov Identifier: NCT03281044
Recruitment Status : Not yet recruiting
First Posted : September 13, 2017
Last Update Posted : October 18, 2018
Sponsor:
Information provided by (Responsible Party):
André Schmidt, Psychiatric Hospital of the University of Basel

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.


Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: Fecal microbiota capsules Drug: Placebo oral capsule Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Oral Frozen Fecal Microbiota Transplantation (FMT) Capsules for Depression: a Double-blind, Placebo-controlled, Randomized Parallel Group Study
Estimated Study Start Date : November 2018
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bowel Movement

Arm Intervention/treatment
Experimental: FMT group
Patient group receiving active FMT capsules
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.

Placebo Comparator: Placebo group
Patient group receiving placebo capsules
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. Brain function (measured Blood-oxygen-level dependent contrast imaging) [ Time Frame: Change from baseline score to follow-up measurement after 1 month ]
    Efficacy measure

  5. HPA axis function (measured with salivary cortisol awakening responses). [ Time Frame: Change from baseline score to follow-up measurement after 1 month ]
    Efficacy measure

  6. Neurogenesis (measured with blood levels of BDNF). [ Time Frame: Change from baseline score to follow-up measurement after 1 month ]
    Efficacy measure

  7. 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

  8. 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

  9. Cognition (measured with the Trail Making Test) [ Time Frame: Change from baseline score to follow-up measurement after 1 month ]
    Efficacy measure

  10. Physical activity (measured with a portable wristwatch). [ Time Frame: Change from baseline score to follow-up measurement after 1 month ]
    Efficacy measure

  11. Sleep quality (measured with 28-channel electroencephalography) [ Time Frame: Change from baseline score to follow-up measurement after 1 month ]
    Efficacy measure



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03281044


Contacts
Contact: André Schmidt 613255929 andre.schmidt@unibas.ch

Locations
Switzerland
University Psychiatric Clinics (UPK)
Basel, Switzerland, 4012
Sponsors and Collaborators
Psychiatric Hospital of the University of Basel
Investigators
Principal Investigator: André Schmidt University of Basel, Department of Psychiatry (UPK)

Responsible Party: André Schmidt, Research Group Leader, Psychiatric Hospital of the University of Basel
ClinicalTrials.gov Identifier: NCT03281044     History of Changes
Other Study ID Numbers: 2017-01050
First Posted: September 13, 2017    Key Record Dates
Last Update Posted: October 18, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders