The Gut - PRO Study

Official title

Probiotic Supplementation Safety and Feasibility Study in Preclinical Alzheimer's Disease

Overview

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.

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.

Interventions

• Drug Probiotic
  A single dose of oral PS will be administered once daily for 6 months
• Other Placebo
  A placebo will be given once daily for 6 months.

Primary outcome measures

• 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]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Wisconsin Hospitals and Clinics — Madison

Identifiers

NCT: NCT07413744 · 2024-0622 · 1R61AG088913-01A1 · A534255 · Protocol Version 4/13/26

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗