Fecal Microbiota Transplantation in Depression

NCT ID: NCT03281044

Last Updated: 2020-04-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-24
• Study Completion Date: 2020-03-16

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

FMT group

Patient group receiving active FMT capsules

Group Type: EXPERIMENTAL

Fecal microbiota capsules

Intervention Type: 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.

Placebo group

Patient group receiving placebo capsules

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: 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

Interventions

Fecal microbiota capsules

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.

Intervention Type: 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

Intervention Type: DRUG

Eligibility 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)
• Treatment as usual for depression
• In- and outpatients 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Psychiatric Hospital of the University of Basel

OTHER

Sponsor Role: lead

Responsible Party

André Schmidt

Research Group Leader

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

André Schmidt

Role: PRINCIPAL_INVESTIGATOR

University of Basel, Department of Psychiatry (UPK)

Locations

University Psychiatric Clinics (UPK)

Basel, , Switzerland

Countries

Switzerland

Other Identifiers

2017-01050

Identifier Type: -

Identifier Source: org_study_id