Effects of Doxycycline and Rifampicin on Biomarkers of Alzheimer's Disease in the Cerebrospinal Fluid
Primary Purpose
Alzheimer's Disease
Status
Completed
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
doxycycline
rifampicin
Placebo matched to doxycycline
Placebo matched to Rifampin
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer's Disease focused on measuring doxycycline, rifampicin, cerebrospinal fluid, biomarkers, beta amyloid, tau
Eligibility Criteria
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
Sites / Locations
- St.Peter's Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
1 AD combined doxycycline + rifampin
2 AD Doxycycline only
3 Rifampin only
4 Double Placebo
Arm Description
Doxycycline 100 mg b.i.d. plus rifampin 300 mg o.d. for 12 months.
Doxycycline 100 mg b.i.d. plus placebo matched to rifampin o.d. for 12 months.
Rifampin 300 mg o.d. plus placebo matched to doxycycline b.i.d. for 12 months.
Placebo matched to Doxycycline b.i.d. plus placebo matched to rifampin o.d. for 12 months.
Outcomes
Primary Outcome Measures
Clinical Dementia Rating scale
Standardized Alzheimer's disease Assessment Scale -cognitive subscale
Secondary Outcome Measures
Full Information
NCT ID
NCT00439166
First Posted
February 20, 2007
Last Updated
March 15, 2018
Sponsor
Hamilton Health Sciences Corporation
Collaborators
The Physicians' Services Incorporated Foundation
1. Study Identification
Unique Protocol Identification Number
NCT00439166
Brief Title
Effects of Doxycycline and Rifampicin on Biomarkers of Alzheimer's Disease in the Cerebrospinal Fluid
Official Title
Effects of Treatment With Doxycycline and Rifampicin on Biomarkers of Alzheimer's Disease in the Cerebrospinal Fluid
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
February 2007 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
December 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hamilton Health Sciences Corporation
Collaborators
The Physicians' Services Incorporated Foundation
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
doxycycline, rifampicin, cerebrospinal fluid, biomarkers, beta amyloid, tau
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Non-Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1 AD combined doxycycline + rifampin
Arm Type
Experimental
Arm Description
Doxycycline 100 mg b.i.d. plus rifampin 300 mg o.d. for 12 months.
Arm Title
2 AD Doxycycline only
Arm Type
Experimental
Arm Description
Doxycycline 100 mg b.i.d. plus placebo matched to rifampin o.d. for 12 months.
Arm Title
3 Rifampin only
Arm Type
Experimental
Arm Description
Rifampin 300 mg o.d. plus placebo matched to doxycycline b.i.d. for 12 months.
Arm Title
4 Double Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo matched to Doxycycline b.i.d. plus placebo matched to rifampin o.d. for 12 months.
Intervention Type
Drug
Intervention Name(s)
doxycycline
Intervention Description
capsule, 100 mg, b.i.d., daily for 1 year
Intervention Type
Drug
Intervention Name(s)
rifampicin
Other Intervention Name(s)
Rofact, Rifadin
Intervention Description
capsule, 300mg, o.d., daily for 11 months (administration starts in 2nd month of trial)
Intervention Type
Drug
Intervention Name(s)
Placebo matched to doxycycline
Intervention Description
Doxycycline-matched - blue capsule, b.i.d.,daily for 12 months
Intervention Type
Drug
Intervention Name(s)
Placebo matched to Rifampin
Intervention Description
Rifampin-matched - red capsule, o.d., daily for 11 months starting at month 2.
Primary Outcome Measure Information:
Title
Clinical Dementia Rating scale
Time Frame
12 months
Title
Standardized Alzheimer's disease Assessment Scale -cognitive subscale
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William Molloy, MB, FRCPC
Organizational Affiliation
McMaster University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Tricia KW Woo, MD, FRCPC
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David D Cowan, MD, FRCPC
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Brandon M Kucher, PhD
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alwin Cunje, MD, PhD
Organizational Affiliation
University of Ottawa
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Tim I Standish, MA
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
Facility Information:
Facility Name
St.Peter's Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8M1W9
Country
Canada
12. IPD Sharing Statement
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Effects of Doxycycline and Rifampicin on Biomarkers of Alzheimer's Disease in the Cerebrospinal Fluid
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