Trial of Rifaximin in Probable Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Rifaximin 550 milligrams (MG)
Intervention description: 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.
Intervention MeSH terms: Rifaximin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 55 Years
Maximum age: 85 Years
Healthy volunteers: No

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.
    

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