Oral Fecal Microbiota Transplant Feasibility Study in Alzheimer's Disease

NCT03998423 | Terminated Phase 1 FDA Drug

• 4 other identifiers: AMBITION2018-0283A534255SMPH/MEDICINE/MEDICINE
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to assess the safety and feasibility of an oral fecal microbiota transplant (FMT) intervention for Alzheimer's disease (AD).

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (6)

• Safety: Proportion of participants with treatment-related adverse events, serious adverse events, or adverse events of special interest.

  Proportion of participants with treatment-related adverse events, serious adverse events, or adverse events of special interest. Adverse events, serious adverse events, or adverse events of special interest, will be evaluated following study procedures using AE and SAE forms, telephone and in person interview, and relevant medical records related to adverse events.

  1 year

• Feasibility: Participant recruitment rate

  Number of weeks/months needed to meet study group numbers.

  1 year

• Feasibility: Eligibility

  Proportion of individuals expressing interest who meet inclusion/exclusion criteria.

  1 year

• Feasibility: Procedures completed.

  Proportion of participants able to complete procedures (including FMT) will be part of feasibility.

  1 year

• Feasibility: Retention

  Proportion of participants that complete follow up.

  1 year

• Change in gut composition: Engraftment of fecal microbial transplant as assessed by 16S rRNA sequencing of recipient stool sample

  In order to determine efficacy of fecal transplant, change in composition, i.e. microbial engraftment will be assessed by testing for newly detected operational taxonomic units (OTUs) in the gut microbiome of a participant post-FMT (which were present in the donor but undetected in the participant pre-FMT). This will be assessed via 16S rRNA seq of recipient stool samples pre- and post- FMT.

  baseline, 8 weeks, 24 weeks, 1 year

Secondary Outcomes (17)

• Cognition: Change in Montreal Cognitive Assessment (MoCA) score

  baseline and 1 year

• Cognition: Change in results of Repeatable Battery for the Assessment of Neuropsychological Status

  baseline and 1 year

• Cognition: Change in the results of Trail Making Test Part A and Part B

  baseline and 1 year

• Metabolic/physiological measure: Change in the level of Hemoglobin A1C

  baseline, 8 weeks, 24 weeks, and 1 year

• Metabolic/physiological measure: Change in the level of fasting glucose

  baseline, 8 weeks, 24 weeks, and 1 year

Study Arms (3)

1 dose fecal microbiota transplant

EXPERIMENTAL

This group will receive one dose of Fecal Microbiota Transplant (FMT) at baseline.

Biological: Fecal Microbiota Transplant

2 doses fecal microbiota transplant

EXPERIMENTAL

This group will will receive one dose of Fecal Microbiota Transplant (FMT) at baseline and a second dose of FMT 8 weeks later.

Biological: Fecal Microbiota Transplant

3 doses fecal microbiota transplant

EXPERIMENTAL

This group will will receive one dose of Fecal Microbiota Transplant (FMT) at baseline, second dose of FMT at 8 weeks, and a third dose of FMT at 12 weeks.

Biological: Fecal Microbiota Transplant

Interventions

Fecal Microbiota Transplant BIOLOGICAL

Double-encapsulated Fecal Microbiota Transplant Capsules

Also known as: FMT Capsule DE

1 dose fecal microbiota transplant; 2 doses fecal microbiota transplant; 3 doses fecal microbiota transplant

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Current enrollment in the Wisconsin ADRC clinical core study (2011-0030), ADCP (26695, MCW IRB), or referred from clinic
• At least 45 years of age

You may not qualify if:

• Willing and able to comply with all study procedures for the duration of the study
• Able to provide signed and date informed consent form
• Participant is not pregnant, lactating or of childbearing potential (ie women must be two years post-menopausal or surgically sterile
• Males must agree to avoid impregnation of women during and for four weeks after completing study treatment through use of an acceptable method of contraception
• Able to take oral medications
• Able to take the test capsule successfully with no signs or symptoms of dysphagia
• Abnormal memory function documented by neuropsychological testing
• Wisconsin ADRC (HS IRB# 2015-0030) Consensus Diagnosis Conference indicates probable AD diagnosis as per NINDS/ADRDA criteria for probable AD (for ADRC and ADCP participants only).
• Active or previous (within 6 months) participation in an Alzheimer's clinical intervention/trial
• Significant neurologic disease: Any significant neurologic disease, such as Parkinson's disease, stroke, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, subdural hematoma, multiple sclerosis, seizure disorder, or other significant deficits (other than Alzheimer's dementia)
• Alcohol/substance: history of alcohol/substance dependence since joining the cohort
• Psychiatric disorders: Untreated current axis 1 DSM-V disorder such as major untreated depression, current untreated bipolar 1 disorder, untreated schizophrenia spectrum disorders, or other conditions potentially affecting study adherence.
• Significant medical illness: any significant systemic illness or unstable medical condition occurring that could affect cognition (other than Alzheimer's). Examples include malignant cancer, chemotherapy, untreated thyroid disease, heart failure, or renal insufficiency.
• Illiterate, blind, or non-English speaking
• Known periodic antibiotic use (i.e. prior to dental appointments)

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Wisconsin Partnership Program: collaborator

Study Sites (1)

University of Wisconsin - Madison

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC, Carlsson CM, Asthana S, Zetterberg H, Blennow K, Bendlin BB, Rey FE. Gut microbiome alterations in Alzheimer's disease. Sci Rep. 2017 Oct 19;7(1):13537. doi: 10.1038/s41598-017-13601-y.

  PMID: 29051531 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Barbara Bendlin, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A single dose of 30 capsules (22.5g) of oral FMT will be given once (week 0), twice (week 0 and week 8), or three times (week 0, week 8, and week 24). Participants are randomly assigned to 1, 2, or 3 doses of FMT.

Study Record Dates

• First Submitted: August 23, 2018
• First Posted: June 26, 2019
• Study Start: November 14, 2019
• Primary Completion: July 14, 2020
• Study Completion: July 14, 2020
• Last Updated: July 24, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)