Trial Outcomes & Findings for Trial of Rifaximin in Probable Alzheimer's Disease (NCT NCT03856359)

NCT ID: NCT03856359

Last Updated: 2021-12-17

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 10 participants
• Primary outcome timeframe: 5 months
• Results posted on: 2021-12-17

Participant Flow

Subjects recruited from referrals and the community via advertisement. Subjects and caregivers compensated for participation in the study to cover travel and time.

Participant milestones

Measure	Rifaximin rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.
Overall Study STARTED	10
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Trial of Rifaximin in Probable Alzheimer's Disease

Baseline characteristics by cohort

Measure	Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants
Age, Continuous	72 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: 5 months

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.

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Number of Participants Experiencing Diarrhea Caused by Clostridium Difficile

5 Participants

PRIMARY outcome

Timeframe: At baseline and at 3 months

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.

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Change in ADAS Cog 11 Scores

30.5 score on a scale Interval 30.3 to 31.0

SECONDARY outcome

Timeframe: Baseline, 3 months, 5 months

Assessed at every visit. The patients will be followed closely to see if they are tolerating the drug, Rifaximin. The of the number of side effects would indicate that the patient may not be tolerating the drug. Most of these side effects are minor and include headache, nausea, vomiting, tiredness. A potentially fatal side effect would be the development of clostridium difficile diarrhea. 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.

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

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

7 Participants

SECONDARY outcome

Timeframe: Baseline, 3 months

Change from baseline global cognitive scores at month 3). Global cognitive performance will be assessed by a psychometrician using the (MMSE). It is a brief cognitive questionnaire with a maximum score of 30 points. MMSE range is 0-30 with lower scores indicating worse performance. The number of correct answers is added to generate the total score.

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

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

-0.3 score on a scale Interval -1.8 to 1.2

SECONDARY outcome

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

Emergent AEs that required a change in safety measures. These were AEs that were found when talking to or examining the subjects.

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

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

0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 3 months

Change in ammonia levels following treatment with Rifaximin.

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Changes From Baseline in Ammonia Level

0.1 mg/dL Interval -7.06 to 7.25

SECONDARY outcome

Timeframe: Baseline to 3 months

Observing for development of diarrhea due to Clostridium difficile

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Development of Clostridium Difficile Diarrhea

0 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, 3 months

Change in serum Total tau after 3 months Rifaximin administration.

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Total Tau

-0.17 ng/mL Interval -0.61 to 0.26

SECONDARY outcome

Timeframe: at baseline and at 3 months

Change in Phosphorylated tau following 3 months oral Rifaximin

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Phosphorylated Tau

-0.39 ng/mL Interval -1.07 to 0.3

SECONDARY outcome

Timeframe: Baseline, 3 months

Change in Glial Fibrillary Acidic Protein (GFAP) after 3 months of oral Rifaximin

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Change in Glial Fibrillary Acidic Protein (GFAP)

-39.76 pg/mL Interval -99.46 to 19.93

SECONDARY outcome

Timeframe: Baseline, 3 months

Change in Neurofilament Light levels after Rifaximin for 3 months

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Change in Neurofilament Light (Nfl) Levels

-4.22 ng/L Interval -6.71 to -1.72

SECONDARY outcome

Timeframe: Baseline, 3 months

Change in Interleukin 10 following 3 months Rifaximin

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Change in Interleukin 10 (IL-10)

00.70 pg/mL Interval -4.85 to 3.46

SECONDARY outcome

Timeframe: Baseline, 3 months

Interleukin 13 levels after Rifaximin

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Changes in Interleukin 13 (IL-13) Following Treatment With Rifaximin

-1.78 pg/mL Interval -3.9 to 0.33

SECONDARY outcome

Timeframe: Baseline, 3 months

Change in Interleukin 1B following Rifaximin

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Change in Interleukin 1B (IL-1B)

-0.1 pg/mL Interval -2.06 to 1.87

SECONDARY outcome

Timeframe: Baseline, 3 months

Population: 10 patients with Alzheimer's Disease

Change in Interleukin 2 following Rifaximin

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Change in Interleukin 2 (IL-2)

-0.33 pg/mL Interval -0.93 to 0.27

SECONDARY outcome

Timeframe: Baseline, 3 months

Change in Interleukin 4 after Rifaximin

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Change in Interleukin 4 (IL-4)

-17.40 pg/mL Interval -68.73 to 33.93

SECONDARY outcome

Timeframe: Baseline, 3 months

Change in Interleukin 5 after Rifaximin

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Change in Interleukin 5 (IL-5)

-0.87 pg/mL Interval -2.34 to 0.6

SECONDARY outcome

Timeframe: Baseline, 3 months

Change in Interleukin 8 after Rifaximin

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Change in Interleukin 8 (IL-8)

-1.31 pg/mL Interval -5.81 to 3.2

SECONDARY outcome

Timeframe: Baseline, 3 months

Change in Interleukin 6 following Rifaximin

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Change in Interleukin 6 (IL-6)

-1.62 pg/mL Interval -3.39 to 0.15

SECONDARY outcome

Timeframe: Baseline, 3 months

Change in Tumor Necrosis Factor a

Outcome measures

Measure

Rifaximin n=10 Participants rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.

Change in Tumor Necrosis Factor a

-0.46 pg/mL Interval -1.55 to 0.64

Adverse Events

Rifaximin

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Rifaximin n=10 participants at risk rifaximin 550 milligrams (mg) orally twice daily for 3 months Rifaximin 550 milligrams (MG): 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.
Nervous system disorders Decline in cognitive ability	10.0% 1/10 • Number of events 1 • 1 year, 1 month
Nervous system disorders Increased confusion	10.0% 1/10 • Number of events 1 • 1 year, 1 month
Gastrointestinal disorders Upset stomach	10.0% 1/10 • Number of events 1 • 1 year, 1 month
Gastrointestinal disorders Diarrhea	40.0% 4/10 • Number of events 4 • 1 year, 1 month
Nervous system disorders Hand tremor	10.0% 1/10 • Number of events 1 • 1 year, 1 month
Musculoskeletal and connective tissue disorders Fell out of chair	10.0% 1/10 • Number of events 1 • 1 year, 1 month
Musculoskeletal and connective tissue disorders Fell	10.0% 1/10 • Number of events 1 • 1 year, 1 month

Additional Information

Dr. Paul V. Suhocki

Duke University Hospital

Phone: 919-684-7284

Email: suhoc001@mc.duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place