Overview

This trial is active, not recruiting.

Condition alzheimer's disease
Treatments doxycycline, rifampicin, placebo matched to doxycycline, placebo matched to rifampin
Phase phase 3
Sponsor Hamilton Health Sciences Corporation
Collaborator The Physicians' Services Incorporated Foundation
Start date February 2007
End date April 2010
Trial size 100 participants
Trial identifier NCT00439166, PSI 06-47

Summary

This study will determine if biomarkers found in the cerebrospinal fluid of people with Alzheimer's disease, are affected by treatment with two common antibiotics, doxycycline and rifampicin, suggesting a disease-modifying effect of those treatments.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Intervention model factorial assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Doxycycline 100 mg b.i.d. plus rifampin 300 mg o.d. for 12 months.
doxycycline
capsule, 100 mg, b.i.d., daily for 1 year
rifampicin Rofact
capsule, 300mg, o.d., daily for 11 months (administration starts in 2nd month of trial)
(Experimental)
Doxycycline 100 mg b.i.d. plus placebo matched to rifampin o.d. for 12 months.
doxycycline
capsule, 100 mg, b.i.d., daily for 1 year
placebo matched to rifampin
Rifampin-matched - red capsule, o.d., daily for 11 months starting at month 2.
(Experimental)
Rifampin 300 mg o.d. plus placebo matched to doxycycline b.i.d. for 12 months.
rifampicin Rofact
capsule, 300mg, o.d., daily for 11 months (administration starts in 2nd month of trial)
placebo matched to doxycycline
Doxycycline-matched - blue capsule, b.i.d.,daily for 12 months
(Placebo Comparator)
Placebo matched to Doxycycline b.i.d. plus placebo matched to rifampin o.d. for 12 months.
placebo matched to doxycycline
Doxycycline-matched - blue capsule, b.i.d.,daily for 12 months
placebo matched to rifampin
Rifampin-matched - red capsule, o.d., daily for 11 months starting at month 2.

Primary Outcomes

Measure
Clinical Dementia Rating scale
time frame: 12 months
Standardized Alzheimer's disease Assessment Scale -cognitive subscale
time frame: 12 months

Eligibility Criteria

Male or female participants at least 50 years old.

Inclusion Criteria: - Male or female - Age greater than or equal to 50 years - Diagnosis of probable Alzheimer's disease by NINCDS-ADRDA criteria - Standardized Mini-Mental State Examination score 14-26 inclusive - A caregiver who consents to monitor study medications, report on patient function, bring the patient to visits, etc. - Vision, hearing, language ability sufficient to complete standardized testing in English. - Patient consents (or legal representative consents for patient) - Generally stable level of health where patient may be reasonably expected to complete a 1 year trial Exclusion Criteria: - Other neurodegenerative diseases such as Lewy body or Parkinson's - Cognitive impairment due to: acute trauma, subdural hematoma, hypoxic cerebral damage, B12 deficiency, infections such as AIDS or meningitis, cerebral neoplasia, endocrine deficiencies, mental retardation - Significant cerebrovascular disease or multi-infarct dementia - Intra-cranial pathology such as tumour - Co-existing medical conditions such as epilepsy, major psychiatric conditions, depression (Cornell Depression in Dementia Scale score of 12 or more), significant liver, kidney, lung, metabolic or endocrine diseases - Clinically significant cardiac disease such as uncontrolled angina or hypertension - Anti-dementia treatments other than donepezil, galantamine, rivastigmine, memantine - Enrollment in trials with other investigational drugs - Antibiotic use more than one month in the last six months - Allergy to doxycycline or rifampicin

Additional Information

Official title Effects of Treatment With Doxycycline and Rifampicin on Biomarkers of Alzheimer's Disease in the Cerebrospinal Fluid
Principal investigator Tricia KW Woo, MD, FRCPC
Description Diagnostic markers in the cerebrospinal fluid (CSF) have become a rapidly growing research field. Potential disease-modifying drugs like the antibiotics rifampicin and doxycycline, highlight the need of improved diagnostic accuracy and offer the potential to examine how these treatments may actually exert their clinical effects. Cerebrospinal fluid biomarkers (the 42 amino acid form of β-amyloid (Aβ), total tau, and phosphorylated tau) have been evaluated in scientific studies. Tau proteins are considered "state" markers, whereas Aβ(1-42) proteins can be used as "stage" markers. These CSF markers have high sensitivity to differentiate early AD from normal aging, depression, alcohol dementia and Parkinson's disease. When these biomarkers are used in combination with a medical history, clinical examination, laboratory tests and brain imaging, the diagnostic accuracy is improved. Matrix metalloproteinase (MMP) dysregulation is thought to contribute to a variety of pathological conditions such as arthritis, cancer, atherosclerosis, aneurysms, nephritis, tissue ulcers, and fibrosis. In addition, MMP involvement has been demonstrated in the pathogenesis of a variety of CNS disorders, including bacterial and viral disorders, stroke, multiple sclerosis, ALS, and AD. There is an inflammatory response in AD. This includes complement activation, elevated C-reactive protein (CRP), elevated pro-inflammatory cytokines (including IL-1-β, IL-6, TNF-α, TGF-β, S100-β), chemokine alterations (IL-8, MIP-1-α, MIP-1-β, MCP-1), and microglial. We are measuring the biochemical markers of Aβ(1-40) and Aβ(1-42), P-tau and T-tau, matrix metalloproteinases (MMP-2, MMP-9), pro-inflammatory cytokines (IL-1beta, TNF-alpha), and anti-inflammatory cytokines (IL-4 and IL-10) at the start and one year after treatment in the multi-centered, randomized, controlled, trial of disease-modifying drugs rifampicin and/or and doxycycline to slow the progress of Alzheimer's disease by affecting the production of these biomarkers.
Trial information was received from ClinicalTrials.gov and was last updated in July 2010.
Information provided to ClinicalTrials.gov by McMaster University.