Back to results

Fecal Microbiota Transplantation in Depression

Primary Purpose

Major Depressive Disorder

Status

Terminated

Phase

Phase 2

Locations

Switzerland

Study Type

Interventional

Intervention

Fecal microbiota capsules

Placebo oral capsule

About this trial

This is an interventional treatment trial for Major Depressive Disorder

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University Psychiatric Clinics (UPK)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

FMT group

Placebo group

Arm Description

Patient group receiving active FMT capsules

Patient group receiving placebo capsules

Outcomes

Primary Outcome Measures

Depressive symptoms as measured with the Hamilton Rating Scale for Depression

Efficacy measure

Secondary Outcome Measures

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

Efficacy measure

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

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))

Efficacy measure

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

Efficacy measure

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

Efficacy measure

Neurogenesis (measured with blood levels of BDNF).

Efficacy measure

Appetite-regulating hormones (measured with blood levels of ghrelin and leptin).

Efficacy measure

Immunoregulation and inflammation (measured with blood levels of macrophage migration inhibitory factor and interleukin 1 beta).

Efficacy measure

Cognition (measured with the Trail Making Test)

Efficacy measure

Physical activity (measured with a portable wristwatch).

Efficacy measure

Sleep quality (measured with 28-channel electroencephalography)

Efficacy measure

Full Information

NCT ID

NCT03281044

First Posted

September 4, 2017

Last Updated

April 15, 2020

Sponsor

Psychiatric Hospital of the University of Basel

1. Study Identification

Unique Protocol Identification Number

NCT03281044

Brief Title

Fecal Microbiota Transplantation in Depression

Official Title

Oral Frozen Fecal Microbiota Transplantation (FMT) Capsules for Depression: a Double-blind, Placebo-controlled, Randomized Parallel Group Study

Study Type

Interventional

2. Study Status

Record Verification Date

April 2020

Overall Recruitment Status

Terminated

Why Stopped

Although not observed in our patients (4 enrolled), SAEs have been reported in other patients receiving the same product.

Study Start Date

October 24, 2018 (Actual)

Primary Completion Date

March 16, 2020 (Actual)

Study Completion Date

March 16, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Psychiatric Hospital of the University of Basel

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Major Depressive Disorder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

FMT group

Arm Type

Experimental

Arm Description

Patient group receiving active FMT capsules

Arm Title

Placebo group

Arm Type

Placebo Comparator

Arm Description

Patient group receiving placebo capsules

Intervention Type

Drug

Intervention Name(s)

Fecal microbiota capsules

Intervention 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.

Intervention Type

Drug

Intervention Name(s)

Placebo oral capsule

Intervention 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

Primary Outcome Measure Information:

Title

Depressive symptoms as measured with the Hamilton Rating Scale for Depression

Description

Efficacy measure

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

Efficacy measure

Time Frame