Oral Fecal Microbiota Transplant Feasibility Study in Alzheimer's Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Safety: Proportion of participants with treatment-related adverse events, serious adverse events, or adverse events of special interest.
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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).
排除标准
- •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)
- •Oral FMT-specific exclusion criteria:
- •Inability (e.g. dysphagia) or unwilling to swallow capsules - assessed using the Eating Assessment Tool (EAT-10) and bedside 3oz water swallow test administered by CRU nurse or study coordinator
- •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 < 6 months
- •Previous FMT or microbiome-based products at any time excluding this study
- •Patients with severe anaphylactic or anaphylactoid food allergy
- •Solid organ transplant recipients ≤ 90 days post-transplant or on active treatment for rejection
- •Immunocompromised/ at risk of CMV/EBV associated disease
- •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
- •Exclusionary factors affecting the microbiome:
- •Use of systemic antibiotics (intravenous, intramuscular, or oral) in the previous 3 months
- •Oral, intravenous, intramuscular, nasal or inhaled corticosteroids (except PRN use for allergies)
- •Immune stimulating medications
- •Methotrexate or immunosuppressive cytotoxic agents
- •Large doses of commercial probiotics consumed (greater than or equal to 108 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).
- •Unstable dietary history during the previous month, which is defined as major changes in diet by eliminating or significantly increasing a major good 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 including 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
结局指标
主要结局
Safety: Proportion of participants with treatment-related adverse events, serious adverse events, or adverse events of special interest.
时间窗: 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
时间窗: 1 year
Number of weeks/months needed to meet study group numbers.
Feasibility: Eligibility
时间窗: 1 year
Proportion of individuals expressing interest who meet inclusion/exclusion criteria.
Feasibility: Procedures completed.
时间窗: 1 year
Proportion of participants able to complete procedures (including FMT) will be part of feasibility.
Feasibility: Retention
时间窗: 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
时间窗: 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.
次要结局
- 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)
- Change in physical activity as measured by Actigraphy watch(baseline, 24 weeks, 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)
- Metabolic/physiological measure: Change in the level of fasting insulin(baseline, 8 weeks, 24 weeks, and 1 year)
- Metabolic/physiological measure: Change in the blood lipid profile(baseline, 8 weeks, 24 weeks, and 1 year)
- Metabolic/physiological measure: Change in the blood pressure(baseline, 8 weeks, 24 weeks, and 1 year)
- Metabolic/physiological measure: Change in body weight(baseline, 8 weeks, 24 weeks, and 1 year)
- Metabolic/physiological measure: Change in the body composition by measuring body fat percentage(baseline and 1 year)
- Change in insulin resistance indexed by the homeostatic model assessment-insulin resistance (HOMA-IR) method(baseline, 8 weeks, 24 weeks, and 1 year)
- Function: Change in total score on the Bristol Activities of Daily Living Scale(baseline and 1 year)
- Metabolic/physiological measure: Change in the level of C-reactive protein(baseline, 8 weeks, 24 weeks, and 1 year)
- Change in CSF biomarkers(baseline and 1 year)
- 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 Sleep as measured by Actigraphy watch(baseline, 24 weeks, and 1 year)