Trial of Rifaximin in Probable Alzheimer's Disease

NCT03856359 | Completed Phase 2 Results FDA Drug

• 1 other identifier: Pro00093318
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (2)

• Number of Participants Experiencing Diarrhea Caused by Clostridium Difficile

  Collected at every visit and follow-up phone visits. A rare side effect of Rifaximin is diarrhea caused by clostridium difficile. This is a very serious form of diarrhea that can be fatal if not treated. The investigators will be following the patients closely during treatment and for 2 months following treatment to see if the patient has any signs or symptoms of this diarrhea. If a patient does develop clostridium difficile diarrhea, they will be promptly treated.

  5 months

• Change in ADAS Cog 11 Scores

  Change in Alzheimer's Disease Assessment Scale - Cognition test with 11 tasks (ADAS Cog 11) scores following 3 months of oral Rifaximin. Scores range from minimum 0 - maximum 70. Higher scores mean worse outcome.

  At baseline and at 3 months

Secondary Outcomes (18)

• Change in Tolerability as Measured by Number of Adverse Events (AE).

  Baseline, 3 months, 5 months

• Change in Cognitive Performance on the Mini-Mental State Exam (MMSE)

  Baseline, 3 months

• Participants With Treatment Emergent Adverse Events as Reported by the Subject That Required a Change in Safety Measures

  Safety will be measured through adverse events throughout study, at month 3 and by phone call at month 5 (2 months after treatment termination).

• Changes From Baseline in Ammonia Level

  Baseline, 3 months

• Development of Clostridium Difficile Diarrhea

  Baseline to 3 months

Study Arms (1)

Rifaximin

EXPERIMENTAL

rifaximin 550 milligrams (mg) orally twice daily for 3 months

Drug: Rifaximin 550 milligrams (MG)

Interventions

Rifaximin 550 milligrams (MG) DRUG

Rifaximin (Xifaxan, Salix Pharmaceuticals, Bridgewater, N.J.) (See Package Insert) is a drug that is approved by the FDA for use in humans for the treatment of Hepatic Encephalopathy, Traveler's Diarrhea and Irritable Bowel Syndrome. It is commercially available. It will be used in accordance with approved labeling as pertains to dosage and administration for Hepatic Encephalopathy, contraindications and warnings. However, it will be used investigationally in this trial as rifaximin is not FDA approved for the treatment of Alzheimer's Disease.

Rifaximin

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• · 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• Bausch Health Americas, Inc.: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Dr. Paul V. Suhocki
• Organization: Duke University Hospital

suhoc001@mc.duke.edu

919-684-7284

Study Officials

• Paul Suhocki, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2019
• First Posted: February 27, 2019
• Study Start: April 9, 2019
• Primary Completion: November 19, 2020
• Study Completion: November 19, 2020
• Last Updated: December 17, 2021
• Results First Posted: December 17, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)