NCT00439166

Effects of Doxycycline and Rifampicin on Biomarkers of Alzheimer's Disease in the Cerebrospinal Fluid

Effects of Treatment With Doxycycline and Rifampicin on Biomarkers of Alzheimer's Disease in the Cerebrospinal Fluid

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 100 (actual)
• Sponsor: Hamilton Health Sciences Corporation · Academic / Other
• Sex: All
• Age: 50 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Alzheimer's Disease

Interventions

Type	Name	Description
DRUG	doxycycline	capsule, 100 mg, b.i.d., daily for 1 year
DRUG	rifampicin	capsule, 300mg, o.d., daily for 11 months (administration starts in 2nd month of trial)
DRUG	Placebo matched to doxycycline	Doxycycline-matched - blue capsule, b.i.d.,daily for 12 months
DRUG	Placebo matched to Rifampin	Rifampin-matched - red capsule, o.d., daily for 11 months starting at month 2.

Timeline

• Start date: 2007-02-01
• Primary completion: 2010-04-01
• Completion: 2010-12-01
• First posted: 2007-02-23
• Last updated: 2018-03-19

Locations

1 site across 1 country: Canada