A Pilot Study of Inflammatory Markers in Alzheimer's Disease

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-05-31

Study Completion Date

2009-10-31

Brief Summary

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The purpose of this study is to examine the cerebrospinal fluid (CSF) of patients with Alzheimer's disease for biomarkers of inflammation and their response to the antibiotics doxycycline and rifampin. The results of this preliminary analysis will be used in defining the direction of further research.

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Detailed Description

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Doxycycline and rifampicin are two antibiotics which may be useful in the treatment of Alzheimer's disease (AD). Besides their antimicrobial effects they may also decrease specific contributors to AD pathology including: 1. amyloid beta, 2. inflammatory mediators, 3. proteolytic enzymes, and 4. metal ions. Evidence indicates an inflammatory response in AD. This includes complement activation, elevated C-reactive protein (CRP), elevated pro-inflammatory cytokines (including IL-1-beta, IL-6, TNF-α, TGF-β, S100-β), chemokine alterations (IL-8, MIP-1-alpha, MIP-1-beta, MCP-1), and microglial activation. In our previous study of AD patients treated with combined doxycycline and rifampicin versus placebo, we demonstrated that antibiotic treatment significantly delayed progression of clinical impairment. Treatment also reduced blood CRP levels suggesting an anti-inflammatory role of these antibiotics. In this study we suggest analysis of biomarkers including both pro and anti-inflammatory cytokines TNF-alpha, IL-1beta, IL-4, IL-10,the chemokine MCP-1 and other inflammatory markers in both the cerebrospinal fluid (CSF) and blood from AD patients and age-matched controls.

AD patients are participants in a 12 month randomized clinical trial of doxycyline and rifampin or placebo (DARAD) for treatment of AD. Each patient is asked if they wish to contribute a sample of CSF and blood at baseline and at 12 months when treatment is completed. About half the patients are consenting to this. Since consent is given to the lumbar puncture before the double-blinded DARAD treatment is initiated, we expect the distribution of samples collected to be random among the four treatment groups. We will compare CSF biomarker levels among the four treatment groups. Ten age-matched healthy controls are also being asked to contribute CSF and blood samples for comparison. The controls are not participants in the DARAD trial.

We feel that this is an important pilot study to determine whether there are any differences in blood or CSF concentrations of commonly studied cytokines between AD patients and normal controls. As such, this study could contribute to the search for a diagnostic biomarker. Also, it could provide a solid foundation for future studies aimed at elucidating the effects of antibiotics on various biomarkers in the blood and CSF of AD patients. From this, we may be able to correlate previous findings that antibiotics delay progression of clinical outcome in AD with changes in blood or CSF biomarker levels.

Conditions

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Alzheimer's Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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1 AD doxycycline + rifampin

Participants with AD allocated to doxycycline 100 mg bid od and rifampin 300 mg od for 12 months

Group Type ACTIVE_COMPARATOR

doxycycline

Intervention Type DRUG

capsule, 100 mg, b.i.d., 12 months

rifampin

Intervention Type DRUG

capsule, 300 mg, od, 12 months

2 AD doxycycline

Group Type ACTIVE_COMPARATOR

doxycycline

Intervention Type DRUG

capsule, 100 mg, b.i.d., 12 months

placebo

Intervention Type DRUG

placebo matched to rifampin; placebo matched to doxycycline

3 AD rifampin

Participants with AD allocated to rifampin 300 mg od od and placebo matched to doxycycline bid for 12 months

Group Type ACTIVE_COMPARATOR

rifampin

Intervention Type DRUG

capsule, 300 mg, od, 12 months

placebo

Intervention Type DRUG

placebo matched to rifampin; placebo matched to doxycycline

4 AD placebo

Participants with AD allocated to placebo matched to doxycycline and placebo matched to rifampin for 12 months

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

placebo matched to rifampin; placebo matched to doxycycline

5 Control

Age-matched cognitively healthy participants (untreated)

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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doxycycline

capsule, 100 mg, b.i.d., 12 months

Intervention Type DRUG

rifampin

capsule, 300 mg, od, 12 months

Intervention Type DRUG

placebo

placebo matched to rifampin; placebo matched to doxycycline

Intervention Type DRUG

Other Intervention Names

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Apo-doxy rifampicin Rofact Rifadin

Eligibility Criteria

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Inclusion Criteria

* Giving informed consent to lumbar puncture
* Participation in the DARAD clinical trial which requires the following:
* diagnosis of probable Alzheimer's disease
* SMMSE 14-26 inclusive
* community-dwelling
* age 50 or greater
* caregiver to monitor study medication and report on ADLs, behaviour, etc.
* adequate English literacy to complete neuropsychological testing
* generally stable level of health

Exclusion Criteria

* Contraindication to lumbar puncture
* dementia due to other neurodegenerative diseases
* cognitive impairment due to head trauma, etc.
* stroke or significant cerebrovascular disease
* clinically significant cardiac disease such as recent MI, uncontrolled hypertension
* taking other anti-dementia treatments or investigational drugs
* allergy to doxycycline or rifampin
* significant psychiatric conditions like depression
* cancer

Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes