Phase 2 Completed N=10 Treatment

Trial of Rifaximin in Probable Alzheimer's Disease

Source: ClinicalTrials.gov NCT03856359 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Dec 2021

Primary outcomePrimary: Number of Participants Experiencing Diarrhea Caused by Clostridium Difficile — 5 Participants

Summary

This study aims to improve cognition and function in patients with Alzheimer's Disease (AD) by administering the oral antibiotic, Rifaximin. Rifaximin is a virtually non-absorbed antibiotic with the unique properties of lowering blood ammonia levels and altering gut microbiota. It is FDA approved for use in patients with hepatic encephalopathy. Rifaximin lowers blood ammonia by altering fecal flora by blocking bacterial RNA synthesis and also by increasing small bowel glutaminase. The Investigators hypothesize that rifaximin will improve cognition and function in AD patients by lowering blood ammonia and / or lowering circulatory pro-inflammatory cytokines secreted by harmful gut bacteria. The Investigators will enroll up to 10 subjects with probable middle stage Alzheimer's Disease. The subjects will be given rifaximin 550 mg orally twice daily for 3 months after evaluation to ensure they have no contraindications. Physician clinical and safety assessments, adverse events, as well as the ADAS-Cog-11 will be administered at baseline and at the 3 month endpoint and two months after stopping treatment (at month 5). Interim safety checks will occur via phone calls one week after baseline and then every 2 weeks till end point. Serum neuronal biomarkers, ammonia levels and pro-inflammatory and anti-inflammatory compounds will also be measured at those times. Bodily fluids (Stool samples) will also be collected. Because of a small risk of developing C. difficile up to 2 months following the last administration of rifaximin, the subjects will be followed for an additional 2 months after the 3 month treatment ends. Rifaximin is contraindicated in patients with hypersensitivity to rifaximin or rifamycin antimicrobials. Hypersensitivity reactions include exfoliative dermatitis, angioneurotic edema, and anaphylaxis. Clostridium difficile associated diarrhea is a risk whenever a patient is maintained chronically on antibiotics, with complications ranging from mild diarrhea to fatal colitis. Drug resistant bacteria can also result from long term use. There is increased systemic exposure to rifaximin in patients with severe hepatic impairment or in patients who are taking P-glycoprotein inhibitors concomitantly. Regarding use in geriatric patients, there were no reported overall differences in the safety of the drug when used in patients 65 years of age or over, when compared with younger subjects.

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants Experiencing Diarrhea Caused by Clostridium Difficile	5	—
PRIMARY Change in ADAS Cog 11 Scores	30.5	0.60
SECONDARY Change in Tolerability as Measured by Number of Adverse Events (AE).	7	—
SECONDARY Change in Cognitive Performance on the Mini-Mental State Exam (MMSE)	-0.3	0.67
SECONDARY Participants With Treatment Emergent Adverse Events as Reported by the Subject That Required a Change in Safety Measures	—	—
SECONDARY Changes From Baseline in Ammonia Level	0.1	0.73
SECONDARY Development of Clostridium Difficile Diarrhea	—	—
SECONDARY Total Tau	-0.17	0.38
SECONDARY Phosphorylated Tau	-0.39	0.23
SECONDARY Change in Glial Fibrillary Acidic Protein (GFAP)	-39.76	0.17
SECONDARY Change in Neurofilament Light (Nfl) Levels	-4.22	0.004 sig
SECONDARY Change in Interleukin 10 (IL-10)	00.70	0.7
SECONDARY Changes in Interleukin 13 (IL-13) Following Treatment With Rifaximin	-1.78	0.09
SECONDARY Change in Interleukin 1B (IL-1B)	-0.1	0.65
SECONDARY Change in Interleukin 2 (IL-2)	-0.33	0.18
SECONDARY Change in Interleukin 4 (IL-4)	-17.40	0.44
SECONDARY Change in Interleukin 5 (IL-5)	-0.87	0.20
SECONDARY Change in Interleukin 8 (IL-8)	-1.31	0.53
SECONDARY Change in Interleukin 6 (IL-6)	-1.62	0.07
SECONDARY Change in Tumor Necrosis Factor a	-0.46	0.36

Eligibility Criteria

Inclusion Criteria

· Probable Alzheimer's Disease (National Institute of Neurological Disorders and Stroke (NINDS) criteria), mild to moderate severity
Ages 55-85; both genders
Mini Mental State Exam (MMSE) scores 10-23
Willing and able to comply with all scheduled clinic visits.
Stable medical health
Has a family or professional caregiver who has regular contact with subject
Ability to consent or legal guardian who can consent
Living at home or in a facility
On no AD therapies or on stable (2 months) concurrent AD therapies

Exclusion Criteria

Past history of C diff infection
Assessment, laboratory examination, physical examination or any other medical condition or circumstance making the volunteer unsuitable for participation in the study in the judgment of the study clinicians
Allergy to Rifaximin
Antibiotic use or hospitalization in the last 6 months
Are taking medications that interact with rifaximin and/or pose a safety risk in the judgment of the PI
Clinically significant abnormal hepatic or renal function
Uncorrected thyroid or B12 abnormalities
Participation in another investigational drug trial in the past 30 days
History of febrile illness within 5 days prior to the study period
Known Hyperammonemia caused by:

Valproic acid Chemotherapy Lung transplant Bariatric surgery Ureterosigmoidoscopy Hyperalimentation Urinary tract infection Errors of metabolism: urea cycle, enzyme deficiencies, organic acidemias, fatty acid oxidation, amino acid transport defects

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03856359). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.