Alzheimer Disease
Conditions
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).
Detailed description
Studies suggests that microbes, including those derived from the gut, may play a role in the development or progression of AD. Gut microbiome composition among individuals with the Alzheimer's clinical syndrome is reduced in microbial diversity and shows compositional differences relative to control groups. Further, genera identified as more abundant in AD are associated with greater AD pathology while genera identified as less abundant in AD are associated with less AD pathology, as shown using CSF biomarkers. The goal of this study is to assess the safety and feasibility of an oral fecal microbiota transplant (FMT) intervention. * Primary Objective: To assess the safety and feasibility (recruitment, eligibility, enrollment, completion, and follow-up) of an oral FMT intervention in people with and without the Alzheimer's clinical syndrome. * Secondary Objective: To demonstrate the effects of FMT on the composition and function of the gut microbiota. To collect preliminary data in order to estimate sample size and other parameters for a larger study.
Interventions
BIOLOGICALFecal Microbiota Transplant
Double-encapsulated Fecal Microbiota Transplant Capsules
Sponsors
Wisconsin Partnership Program
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 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 * Good general health (other than dementia) with no conditions/medications affecting the gut microbiome (see
Exclusion criteria
below) * 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 Additional inclusion criteria for participants with Alzheimer's disease: * 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Proportion of participants with treatment-related adverse events, serious adverse events, or adverse events of special interest. | 1 year | 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. |
| Feasibility: Participant recruitment rate | 1 year | Number of weeks/months needed to meet study group numbers. |
| Feasibility: Eligibility | 1 year | Proportion of individuals expressing interest who meet inclusion/exclusion criteria. |
| Feasibility: Procedures completed. | 1 year | Proportion of participants able to complete procedures (including FMT) will be part of feasibility. |
| Feasibility: Retention | 1 year | Proportion of participants that complete follow up. |
| Change in gut composition: Engraftment of fecal microbial transplant as assessed by 16S rRNA sequencing of recipient stool sample | baseline, 8 weeks, 24 weeks, 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Metabolic/physiological measure: Change in the level of C-reactive protein | baseline, 8 weeks, 24 weeks, and 1 year | Change in the level of C-reactive protein will be assessed |
| Metabolic/physiological measure: Change in the blood lipid profile | baseline, 8 weeks, 24 weeks, and 1 year | Change in the blood lipid profile will be assessed |
| Metabolic/physiological measure: Change in the blood pressure | baseline, 8 weeks, 24 weeks, and 1 year | Change in the blood pressure will be assessed |
| Metabolic/physiological measure: Change in body weight | baseline, 8 weeks, 24 weeks, and 1 year | Change in body weight will be assessed |
| Metabolic/physiological measure: Change in the body composition by measuring body fat percentage | baseline and 1 year | Change in the body composition by measuring body fat percentage |
| Cognition: Change in Montreal Cognitive Assessment (MoCA) score | baseline and 1 year | The Montreal Cognitive Assessment (MoCA) is a cognitive screening test used for detecting cognitive impairment. MoCA scores range between 0 and 30. Lower scores are indicative of impairment |
| Change in physical activity as measured by Actigraphy watch | baseline, 24 weeks, and 1 year | Actigraphy watch will be worn on the non-dominant wrist was used to record a participant's physical activity (total number of active minutes per day). |
| Change in Sleep as measured by Actigraphy watch | baseline, 24 weeks, and 1 year | Actigraphy watch will be worn on the non-dominant wrist to estimate sleep duration. |
| Change in CSF biomarkers | baseline and 1 year | Aβ42, Aβ42/Aβ40, phosphorylated tau, total tau, YKL-40 |
| Change in serum/plasma metabolites on an average of one week pre and post FMT | baseline, week 8, week 24, and 1 year | Change in serum/plasma metabolites on an average of one week pre and post FMT |
| Function: Change in total score on the Bristol Activities of Daily Living Scale | baseline and 1 year | Change in total score on the Bristol Activities of Daily Living Scale. This is a tool used to measure functional ability (ability to independently carry out activities of daily living), and was developed for use with people with dementia. The minimum score is 0. The maximum score is 60. A lower score (better) indicates that a person is independent in their activities of daily living, and a higher score (worse) indicates that the individual is dependent on others. |
| Change in insulin resistance indexed by the homeostatic model assessment-insulin resistance (HOMA-IR) method | baseline, 8 weeks, 24 weeks, and 1 year | Fasting glucose and fasting insulin will be used to calculate HOMA-IR. |
| Cognition: Change in results of Repeatable Battery for the Assessment of Neuropsychological Status | baseline and 1 year | The Repeatable Battery for the Assessment of Neuropsychological Status consists of twelve subtests which give five scores, one for each of the five domains tested (immediate memory, visuospatial/constructional, language, attention, delayed memory). Raw scores on each domain are scaled to account for a person's age. Scaled scores are converted to percentiles which are used to determine a range of performance (impaired, borderline impaired, expected score, high average, superior) and overall cognitive status (impaired/not impaired). |
| Cognition: Change in the results of Trail Making Test Part A and Part B | baseline and 1 year | The Trail Making Test is a neuropsychological test of visual attention and task switching. It consists of two parts, A and B. Participant is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. The test can provide information about visual search speed, scanning, speed of processing, mental flexibility, as well as executive functioning. Results for both TMT A and B are reported as the number of seconds required to complete the task; therefore, higher scores reveal greater impairment. |
| Metabolic/physiological measure: Change in the level of Hemoglobin A1C | baseline, 8 weeks, 24 weeks, and 1 year | Change in the level of Hemoglobin A1C will be assessed |
| Metabolic/physiological measure: Change in the level of fasting glucose | baseline, 8 weeks, 24 weeks, and 1 year | Change in the level of fasting glucose will be assessed |
| Metabolic/physiological measure: Change in the level of fasting insulin | baseline, 8 weeks, 24 weeks, and 1 year | Change in the level of fasting insulin will be assessed |
Countries
United States
Outcome results
None listed