Fecal Microbiota Transplantation in Depression

NCT03281044 | Terminated Phase 2

• 1 other identifier: 2017-01050
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Depressive symptoms as measured with the Hamilton Rating Scale for Depression

  Efficacy measure

  Change from baseline score to follow-up measurements at 1, 2 and 8 months

Secondary Outcomes (11)

• Gut microbiota composition as assessed by 16-S-rRNA sequencing of stool samples

  Change from baseline score to follow-up measurement after 1 month

• Cerebral blood flow (measured with arterial spin labeling, mL/100 g/min^10)

  Change from baseline score to follow-up measurement after 1 month

• 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))

  Change from baseline score to follow-up measurement after 1 month

• Brain function (measured Blood-oxygen-level dependent contrast imaging)

  Change from baseline score to follow-up measurement after 1 month

• HPA axis function (measured with salivary cortisol awakening responses).

  Change from baseline score to follow-up measurement after 1 month

Study Arms (2)

FMT group

EXPERIMENTAL

Patient group receiving active FMT capsules

Drug: Fecal microbiota capsules

Placebo group

PLACEBO COMPARATOR

Patient group receiving placebo capsules

Drug: Placebo oral capsule

Interventions

Fecal microbiota capsules DRUG

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.

FMT group

Placebo oral capsule DRUG

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

Placebo group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)
• Treatment as usual for depression
• In- and outpatients at the UPK Basel

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Psychiatric Hospital of the University of Basel: lead

Study Sites (1)

University Psychiatric Clinics (UPK)

Basel, 4012, Switzerland

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• André Schmidt

  University of Basel, Department of Psychiatry (UPK)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Group Leader

Study Record Dates

• First Submitted: September 4, 2017
• First Posted: September 13, 2017
• Study Start: October 24, 2018
• Primary Completion: March 16, 2020
• Study Completion: March 16, 2020
• Last Updated: April 16, 2020

Record last verified: 2020-04

Locations

CH (1)