Alzheimer's DiseasePhase 3NCT00715858
A Pilot Study of Inflammatory Markers in Alzheimer's Disease
A Phase 3 study testing doxycycline and rifampin in people with Alzheimer's Disease, run by McMaster University at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 50 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- doxycycline and rifampin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteCanada
- Study dates
- May 2008to Oct 2009
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- caregiver to monitor study medication and report on ADLs, behaviour, etc.
- adequate English literacy to complete neuropsychological testing
- generally stable level of health
Who cannot join
- Contraindication to lumbar puncture
- DARAD exclusion criteria as follows:
- 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
Show all 10Show fewer
- taking other anti-dementia treatments or investigational drugs
- allergy to doxycycline or rifampin
- significant psychiatric conditions like depression
- cancer
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
St.Peter's Hospital
Hamilton, Ontario, L8M1W9
D. William Molloy, MB
About this study
Official title: A Pilot Study Comparing Inflammatory Biomarkers in Blood and CSF in Patients With Alzheimer's Disease and Age-Matched Controls
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.
Read the detailed description
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
- Alzheimer's Disease
- Being tested
- doxycycline, rifampin, placebo
- Keywords
- Alzheimer's disease, dementia, inflammation, cytokine, biomarker, cerebrospinal fluid, serum, doxycycline, rifampin
- Medical subject headings
- Alzheimer Disease, Dementia, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
doxycyclineDrug
Also called Apo-doxy
capsule, 100 mg, b.i.d., 12 months
rifampinDrug
Also called rifampicin, Rofact, Rifadin
capsule, 300 mg, od, 12 months
placeboDrug
placebo matched to rifampin; placebo matched to doxycycline
| Study group | Role | What they receive |
|---|---|---|
| 1 AD doxycycline + rifampin | Active comparator | Participants with AD allocated to doxycycline 100 mg bid od and rifampin 300 mg od for 12 months Receives: Drug: doxycycline; Drug: rifampin |
| 2 AD doxycycline | Active comparator | Not described Receives: Drug: doxycycline; Drug: placebo |
| 3 AD rifampin | Active comparator | Participants with AD allocated to rifampin 300 mg od od and placebo matched to doxycycline bid for 12 months Receives: Drug: rifampin; Drug: placebo |
| 4 AD placebo | Placebo comparator | Participants with AD allocated to placebo matched to doxycycline and placebo matched to rifampin for 12 months Receives: Drug: placebo |
| 5 Control | No intervention | Age-matched cognitively healthy participants (untreated) |
What is being measured
The primary outcome is the main question the study is designed to answer.
IL-1beta
Measured: baseline and 12 months
TNF-alpha
Measured: baseline and 12 months
MCP-1
Measured: baseline and 12 months
IL-4
Measured: baseline and 12 month
IL-10
Measured: baseline and 12 months
Secondary outcomes (1)
Other inflammatory markers.
Measured: Baseline and 12 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2008 (estimated)
- Study startMay 2008
- Primary completionAug 2009 (estimated)
- Study completionOct 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- The Physicians' Services Incorporated Foundation
- Investigators
- D.William Molloy, MB, MRCPI, FRCPC, Study chair, McMaster UniversityBrandon M Kucher, PhD, MD, Principal investigator, McMaster UniversityShucui Jiang, MD,PhD, Study director, McMaster UniversityMichel P Rathbone, MB, PhD, Study director, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00715858
- Sponsor's protocol ID
- R07-63
- Status last verified
- Feb 2009
- First submitted
- 11 Jul 2008
- Last updated
- 4 Feb 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
Loeb MB, Molloy DW, Smieja M, Standish T, Goldsmith CH, Mahony J, Smith S, Borrie M, Decoteau E, Davidson W, McDougall A, Gnarpe J, O'DONNell M, Chernesky M. A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer's disease. J Am Geriatr Soc. 2004 Mar;52(3):381-7. doi: 10.1111/j.1532-5415.2004.52109.x.
PubMed 14962152
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study Comparing Inflammatory Biomarkers in Blood and CSF in Patients With Alzheimer's Disease and Age-Matched Controls
- ClinicalTrials.gov ID
- NCT00715858
- Acronym / sponsor ID
- R07-63
- Conditions
- Alzheimer's Disease
- Keywords
- Alzheimer's disease, dementia, inflammation, cytokine, biomarker, cerebrospinal fluid, serum, doxycycline
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- The Physicians' Services Incorporated Foundation
- Study start
- May 2008
- Primary completion
- Aug 2009 (estimated)
- Study completion
- Oct 2009 (estimated)
- First posted
- 15 Jul 2008 (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.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 1 AD doxycycline + rifampin | Active comparator | Drug: doxycycline, Drug: rifampinParticipants with AD allocated to doxycycline 100 mg bid od and rifampin 300 mg od for 12 months |
| 2 AD doxycycline | Active comparator | Drug: doxycycline, Drug: placebo |
| 3 AD rifampin | Active comparator | Drug: rifampin, Drug: placeboParticipants with AD allocated to rifampin 300 mg od od and placebo matched to doxycycline bid for 12 months |
| 4 AD placebo | Placebo comparator | Drug: placeboParticipants with AD allocated to placebo matched to doxycycline and placebo matched to rifampin for 12 months |
| 5 Control | No intervention | –Age-matched cognitively healthy participants (untreated) |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (10 listed)
- Contraindication to lumbar puncture
- DARAD exclusion criteria as follows:
- dementia due to other neurodegenerative diseases
- cognitive impairment due to head trauma, etc.
- stroke or significant cerebrovascular disease
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 |
|---|---|---|
| doxycyclineAlso: Apo-doxycapsule, 100 mg, b.i.d., 12 months | Drug | 1 AD doxycycline + rifampin, 2 AD doxycycline |
| rifampinAlso: rifampicin, Rofact, Rifadincapsule, 300 mg, od, 12 months | Drug | 1 AD doxycycline + rifampin, 3 AD rifampin |
| placeboplacebo matched to rifampin; placebo matched to doxycycline | Drug | 2 AD doxycycline, 3 AD rifampin, 4 AD placebo |
Primary outcome
IL-1beta
Time frame: baseline and 12 months
TNF-alpha
Time frame: baseline and 12 months
MCP-1
Time frame: baseline and 12 months
IL-4
Time frame: baseline and 12 month
IL-10
Time frame: baseline and 12 months
1 secondary outcome
Other inflammatory markers.
Time frame: Baseline and 12 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2009.
- Background: PubMed 14962152Loeb MB, Molloy DW, Smieja M, Standish T, Goldsmith CH, Mahony J, Smith S, Borrie M, Decoteau E, Davidson W, McDougall A, Gnarpe J, O'DONNell M, Chernesky M. A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer's disease. J Am Geriatr Soc. 2004 Mar;52(3):381-7. doi: 10.1111/j.1532-5415.2004.52109.x.
- DARAD Study clinical trial registration on ISRCTN15039674. Details provided.Link provided by the sponsor.
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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.
D.William Molloy, MB, MRCPI, FRCPC study chair
McMaster University
Brandon M Kucher, PhD, MD principal investigator
McMaster University
Shucui Jiang, MD,PhD study director
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 rifampin in people with Alzheimer's Disease, run by McMaster University 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 9 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: status not confirmed, as of the sponsor's last update on 4 Feb 2009. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact D. William Molloy, MB (905-777-3837 ext. 12440, wmolloy@stpetes.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
IL-1beta (time frame: baseline and 12 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00715858, which also lists 1 linked publication.
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 4 Feb 2009.