Alzheimer's DiseasePhase 3NCT00439166
Effects of Doxycycline and Rifampicin on Biomarkers of Alzheimer's Disease in the Cerebrospinal Fluid
A Phase 3 study testing doxycycline and rifampicin in people with Alzheimer's Disease, run by Hamilton Health Sciences Corporation at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- doxycycline and rifampicin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteCanada
- Study dates
- Feb 2007to Dec 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Treatment With Doxycycline and Rifampicin on Biomarkers of Alzheimer's Disease in the Cerebrospinal Fluid
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.
Read the 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
- Being tested
- doxycycline, rifampicin, Placebo matched to doxycycline, Placebo matched to Rifampin
- Keywords
- doxycycline, rifampicin, cerebrospinal fluid, biomarkers, beta amyloid, tau
- Medical subject headings
- Alzheimer Disease, Plaque, Amyloid, Pick Disease of the Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
doxycyclineDrug
capsule, 100 mg, b.i.d., daily for 1 year
rifampicinDrug
Also called Rofact, Rifadin
capsule, 300mg, o.d., daily for 11 months (administration starts in 2nd month of trial)
Placebo matched to doxycyclineDrug
Doxycycline-matched - blue capsule, b.i.d.,daily for 12 months
Placebo matched to RifampinDrug
Rifampin-matched - red capsule, o.d., daily for 11 months starting at month 2.
| Study group | Role | What they receive |
|---|---|---|
| 1 AD combined doxycycline + rifampin | Experimental | Doxycycline 100 mg b.i.d. plus rifampin 300 mg o.d. for 12 months. Receives: Drug: doxycycline; Drug: rifampicin |
| 2 AD Doxycycline only | Experimental | Doxycycline 100 mg b.i.d. plus placebo matched to rifampin o.d. for 12 months. Receives: Drug: doxycycline; Drug: Placebo matched to Rifampin |
| 3 Rifampin only | Experimental | Rifampin 300 mg o.d. plus placebo matched to doxycycline b.i.d. for 12 months. Receives: Drug: rifampicin; Drug: Placebo matched to doxycycline |
| 4 Double Placebo | Placebo comparator | Placebo matched to Doxycycline b.i.d. plus placebo matched to rifampin o.d. for 12 months. Receives: Drug: Placebo matched to doxycycline; Drug: Placebo matched to Rifampin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Dementia Rating scale
Measured: 12 months
Standardized Alzheimer's disease Assessment Scale -cognitive subscale
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2007 (estimated)
- Study startFeb 2007
- Primary completionApr 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hamilton Health Sciences Corporation
- Sponsor type
- University, hospital or other
- Collaborators
- The Physicians' Services Incorporated Foundation
- Responsible party
- Sponsor
- Investigators
- William Molloy, MB, FRCPC, Study chair, McMaster UniversityTricia KW Woo, MD, FRCPC, Principal investigator, McMaster UniversityDavid D Cowan, MD, FRCPC, Principal investigator, McMaster UniversityBrandon M Kucher, PhD, Principal investigator, McMaster UniversityAlwin Cunje, MD, PhD, Principal investigator, University of OttawaTim I Standish, MA, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00439166
- Sponsor's protocol ID
- PSI 06-47
- Status last verified
- Mar 2017
- First submitted
- 20 Feb 2007
- Last updated
- 19 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Treatment With Doxycycline and Rifampicin on Biomarkers of Alzheimer's Disease in the Cerebrospinal Fluid
- ClinicalTrials.gov ID
- NCT00439166
- Acronym / sponsor ID
- PSI 06-47
- Conditions
- Alzheimer's Disease
- Keywords
- doxycycline, rifampicin, cerebrospinal fluid, biomarkers, beta amyloid, tau
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Hamilton Health Sciences CorporationUniversity, hospital or other
- Collaborators
- The Physicians' Services Incorporated Foundation
- Study start
- Feb 2007
- Primary completion
- Apr 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 23 Feb 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 AD combined doxycycline + rifampin | Experimental | Drug: doxycycline, Drug: rifampicinDoxycycline 100 mg b.i.d. plus rifampin 300 mg o.d. for 12 months. |
| 2 AD Doxycycline only | Experimental | Drug: doxycycline, Drug: Placebo matched to RifampinDoxycycline 100 mg b.i.d. plus placebo matched to rifampin o.d. for 12 months. |
| 3 Rifampin only | Experimental | Drug: rifampicin, Drug: Placebo matched to doxycyclineRifampin 300 mg o.d. plus placebo matched to doxycycline b.i.d. for 12 months. |
| 4 Double Placebo | Placebo comparator | Drug: Placebo matched to doxycycline, Drug: Placebo matched to RifampinPlacebo matched to Doxycycline b.i.d. plus placebo matched to rifampin o.d. for 12 months. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| doxycyclinecapsule, 100 mg, b.i.d., daily for 1 year | Drug | 1 AD combined doxycycline + rifampin, 2 AD Doxycycline only |
| rifampicinAlso: Rofact, Rifadincapsule, 300mg, o.d., daily for 11 months (administration starts in 2nd month of trial) | Drug | 1 AD combined doxycycline + rifampin, 3 Rifampin only |
| Placebo matched to doxycyclineDoxycycline-matched - blue capsule, b.i.d.,daily for 12 months | Drug | 3 Rifampin only, 4 Double Placebo |
| Placebo matched to RifampinRifampin-matched - red capsule, o.d., daily for 11 months starting at month 2. | Drug | 2 AD Doxycycline only, 4 Double Placebo |
Primary outcome
Clinical Dementia Rating scale
Time frame: 12 months
Standardized Alzheimer's disease Assessment Scale -cognitive subscale
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William Molloy, MB, FRCPC study chair
McMaster University
Tricia KW Woo, MD, FRCPC principal investigator
McMaster University
David D Cowan, MD, FRCPC principal investigator
McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing doxycycline and rifampicin in people with Alzheimer's Disease, run by Hamilton Health Sciences Corporation at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Dementia Rating scale (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2018.