RecruitingNCT07413744Updated Sep 29, 2026

The Gut - PRO Study

A Phase 1 interventional study of Probiotic and Placebo in Alzheimer Disease, sponsored by University of Wisconsin, Madison. Recruiting at 1 site in United States. Open to participants aged 60 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by University of Wisconsin, Madison · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 40
Allocation: Randomized
Ages: 60 Years and older
Sex: All

Study summary

The purpose of this study is to assess the safety and feasibility of an oral probiotic supplement (PS) intervention in individuals with dementia or mild-cognitive impairment (MCI) due to Alzheimer's disease or at risk of dementia due to Alzheimer's disease (AD). 40 participants will be enrolled and can expect to be on study for up to 1 year.

Read the detailed description

40 participants will be enrolled. 20 with dementia or mild cognitive impairment (MCI) due to Alzheimer's disease (biomarker confirmed amyloid positivity), and 20 unimpaired cognition, enriched for elevated amyloid (approximately 75-80% amyloid positive). Dementia/mild cognitive impairment will be determined according to 2024 NIA-AA criteria.

Primary Objective

To assess the safety and feasibility (recruitment, eligibility, enrollment, completion, and follow-up) of an oral probiotic supplementation (PS) intervention in humans with or at risk for dementia due to AD.

Exploratory Objectives

To demonstrate the effects of PS on the composition and function of the gut microbiota in humans with or at risk for dementia due to AD.
To collect preliminary data in order to estimate sample size and other critical parameters for a larger study.
To examine potential mechanisms by which the gut impacts brain, including leading candidate mechanisms such as intestinal permeability and change to bile acid milieu.

Conditions studied

Alzheimer Disease

Browse trials for

Alzheimer Disease 3,672

Keywords

probiotics

Who can participate

Ages eligible: 60 Years and older
Sexes eligible: All
Accepts healthy volunteers: Yes

Eligibility criteria

Inclusion Criteria:

MCI/AD or cognitively unimpaired, referred from a Wisconsin clinic that is part of the Wisconsin Alzheimer's Institute's (WAI) network, or recruited from the community. May have participated in:
- Alzheimer's Disease Research Center (ADRC) clinical core study (2011-0030)
- ADCP (26695, MCW IRB)
- Synapse study (2018-1283)
- ADRC Recruitment Registry (2016-0735)
At least 60 years of age or older
Good general health (other than cognitive impairment/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 dated informed consent form
Participant is not pregnant, lactating or of childbearing potential (i.e., women must be two years post-menopausal or surgically sterile)
Able to take oral medications
An informant to answer questionnaires about the participant

Additional inclusion criteria for unimpaired participants:

Has MOCA score that falls within the range defined for cognitively healthy individuals

Additional inclusion criteria for participants with MCI/AD

Abnormal cognitive function documented by neuropsychological testing
ADRC (2015-0030) Consensus Diagnosis Conference indicates dementia or MCI due to AD (for ADRC, ADCP, and Synapse participants only)
Meets NIA-AA criteria for MCI or AD.

Exclusion Criteria:

Active or previous (within 6 months) participation in an Alzheimer's clinical intervention/trial (can be included if previously enrolled in placebo or control group)
Standard clinical care for dementia and medications used to treat MCI and Alzheimer's disease are acceptable, including monoclonal antibody therapy
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 or Mild Cognitive Impairment
Alcohol/substance: history of alcohol/substance dependence in the past year.
Significant medical illness: any significant systemic illness or unstable medical condition occurring during ADRC participation that could affect cognition (other than MCI/AD). Examples include malignant cancer, chemotherapy, HIV, untreated thyroid disease, heart failure, or renal insufficiency
Current diagnosis with diabetes
Illiterate, blind, or non-English speaking
Known periodic antibiotic use (i.e., prior to dental appointments)
Oral PS-specific exclusion criteria:
- Inability (e.g., dysphagia) or unwilling to swallow capsules
- Active gastrointestinal infection at time of enrollment
- Known or suspected toxic megacolon and/or known small bowel ileus
- History of total colectomy or bariatric surgery
- Concurrent intensive induction chemotherapy, radiation therapy, or biological treatment for active malignancy
- Unable or unwilling to comply with protocol requirements
- Expected life expectancy less than 6 months
- Previous use of probiotic supplementation (PS) or microbiome-based products within 2 months, large doses of commercial probiotics consumed (greater than or equal to 10\^8 cfu or organisms per day). Includes tablets, capsules, lozenges, chewing gum or powders in which probiotic is a primary component (ordinary dietary components such as fermented beverages/milks, yogurts, foods do not apply). Enrollment after 2 months without probiotic use can be considered for eligibility
- Patients with severe anaphylactic or anaphylactoid food allergy
- Solid organ transplant recipients less than or equal to 90 days post-transplant or on active treatment for rejection
- A condition that would jeopardize the safety or rights of the participant, would make it unlikely for the participant to complete the study, or would confound the results of the study
Exclusionary factors affecting the microbiome:
- Previous use of systemic antibiotics (intravenous, intramuscular, or oral) within 3 months (depends on the duration of antibiotic use, i.e., less than 3 months is considered exclusion, however, enrollment after 3 months without antibiotic use can be considered for eligibility)
- Immune stimulating and/or suppressing medications
- Immunosuppressed as evaluated by complete blood count (CBC) with differential, which includes white blood cell count, total neutrophil count, and total lymphocyte count
- Unstable dietary history during the previous month, which is defined as major changes in diet by eliminating or significantly increasing a major food group
- Major surgery of the GI tract, with the exception of cholecystectomy and appendectomy, in the past five years
- Major bowel resection at any time
- Active uncontrolled gastrointestinal disorders or disease including inflammatory bowel disease, ulcerative colitis (mild-moderate-severe), Crohn's disease (mild-moderate-severe), or indeterminate colitis; irritable bowel syndrome (moderate-severe); persistent, infectious gastroenteritis, colitis, or gastritis; persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection (recurrent) or Helicobacter pylori infection (untreated), or chronic constipation

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Outcomes assessor)
Enrollment: 40 participants (estimated)

Study arms

Experimental
Cognitively Impaired due to AD: Probiotic
Diagnosis of mild cognitive impairment (MCI) or dementia
Drug: Probiotic
Placebo comparator
Cognitively Impaired due to AD: Placebo
Diagnosis of mild cognitive impairment (MCI) or dementia
Other: Placebo
Experimental
Cognitively Unimpaired Amyloid Positive: Probiotic
Drug: Probiotic
Placebo comparator
Cognitively Unimpaired Amyloid Positive: Placebo
Other: Placebo

Interventions

DrugProbiotic
A single dose of oral PS will be administered once daily for 6 months
Also known as: Encapsulated probiotic preparation
OtherPlacebo
A placebo will be given once daily for 6 months.

What researchers measure

Primary outcomes

Safety: Proportion of participants with an adverse event (AE) occurring during any point of the study
Time frame: up to 36 weeks
Safety: Proportion of participants with a severe adverse event (SAE) occurring during any point of the study
Time frame: up to 36 weeks
Feasibility: Number of weeks or months needed to meet study group numbers
Time frame: up to 36 weeks
Feasibility: Proportion of individuals expressing interest in study who are Eligible
Time frame: baseline
Feasibility: Proportion of Participants Who Complete 80 percent of Oral PS
Time frame: week 24
Feasibility: Proportion of Participants Who Complete Intervention
Time frame: up to 36 weeks

Other outcomes

Hemoglobin A1C
Time frame: baseline, week 12, week 24, and week 36
Fasting Glucose
Time frame: baseline, week 12, week 24, week 36
Fasting Insulin
Time frame: baseline, week 12, week 24, week 36
C-reactive protein
Time frame: baseline, week 12, week 24, week 36
Blood lipid profile
Time frame: baseline, week 12, week 24, week 36
Systolic Blood Pressure
Time frame: baseline, week 12, week 24, week 36
Diastolic Blood Pressure
Time frame: baseline, week 12, week 24, week 36
Body Weight
Time frame: baseline, week 12, week 24, week 36
Body Fat Percentage
Time frame: baseline, week 12, week 24, week 36
Insulin Resistance indexed by the homeostatic model assessment-insulin resistance (HOMA-IR) method
Time frame: baseline, week 12, week 24, week 36
Change in Quality of Sleep
General sleep quality will be rated using a 10 item questionnaire, which uses a 6-point Likert scale. Scores range from 10-60, with higher scores indicating better sleep quality.
Time frame: baseline, week 12, week 24, week 36
Metabolites
Measured from serum, plasma, stool
Time frame: baseline, week 12, week 24, week 36
Gut Microbiome Composition
Change in gut microbiome composition will be assessed using 16srRNA seq and metagenomic analysis of stool samples.
Time frame: baseline, week 12, week 24, week 36
Plasma Biomarkers of Alzheimer's Disease Related Dementias (ADRD)
Change in plasma biomarkers of ADRD, including pTau217, neurofilament light chain (NfL), and Glial Fibrillary Acidic Protein (GFAP). Emerging plasma biomarkers may also be assessed.
Time frame: baseline, week 12, week 24, week 36
Change in Montreal Cognitive Assessment (MoCA) score
The MoCA is a cognitive screening test used for detecting cognitive impairment. MoCA scores range between 0 and 30. Lower scores are indicative of impairment.
Time frame: screening, week 24, week 36
Change in Repeatable Battery for the Assessment of Neuropsychological Status: Performance
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).
Time frame: baseline, week 24, week 36
Change in Repeatable Battery for the Assessment of Neuropsychological Status: Cognitive Status
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 overall cognitive status (impaired/not impaired).
Time frame: baseline, week 24, week 36
Change in the results of Trail Making Test (TMT)
The TMT 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.
Time frame: baseline, week 24, week 36
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.
Time frame: baseline, week 12, week 24, week 36
Intestinal Permeability
Investigators may measure proteins or other markers related to intestinal permeability (in blood).
Time frame: baseline, week 12, week 24, week 36
Change in Epworth Sleepiness Scale (ESS)
ESS is an 8 item questionnaire, using a 4-point Likert scale. Scores range from 0-24, with higher scores indicating greater levels of sleepiness throughout the day.
Time frame: baseline, week 12, week 24, week 36
Change in Insomnia Severity Index (ISI)
ISI is an 7 item questionnaire, using a 5-point Likert scale. Scores range from 35-24, with higher scores indicating greater levels of insomnia.
Time frame: baseline, week 12, week 24, week 36
Change in Pittsburgh Sleep Quality Index (PSQI)
PSQI scoring involves summing scores from 7 components, each ranging from 0 (no difficulty) to 3 (severe difficulty), to get a global score from 0 to 21, with higher scores indicating worse sleep quality. A global score over 5 suggests significant sleep difficulties.
Time frame: baseline, week 12, week 24, week 36

Study locations

1 of 1 sites recruiting

University of Wisconsin Hospitals and Clinics
Madison, Wisconsin 53792, United States
- Barbara Bendlin, PhD · Principal investigator
- Federico Rey, PhD · Principal investigator
Recruiting

References and documents

Individual participant data

Plan to share: Yes — Collected specimens (including stool, blood, and CSF) will be stored and may be used for future research. Participants will be asked to consent to the use of the samples for future research.

Supporting information: Study protocol, Sap, Icf

No publications or documents are linked to this record.

Registry details

Key details

Study ID: NCT07413744
Lead sponsor: University of Wisconsin, Madison
Collaborators: International Flavors & Fragrances Inc., National Institute on Aging (NIA)
Responsible party: Sponsor
First posted: Feb 17, 2026
Start date: Oct 2026 (estimated)
Primary completion: Sep 2029 (estimated)
Completion: Sep 2029 (estimated)
Last update: Sep 29, 2026

Study contacts

Alfred Braceros, BA

Contact

braceros@medicine.wisc.edu

608-263-9485

Barbara Bendlin, PhD

principal investigator · UW School of Medicine and Public Health

Federico Rey, PhD

principal investigator · Department of Bacteriology

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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