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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2009 by McMaster University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
The Physicians' Services Incorporated Foundation
Information provided by:
McMaster University
ClinicalTrials.gov Identifier:
NCT00439166
First received: February 20, 2007
Last updated: July 27, 2010
Last verified: September 2009
  Purpose

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.


Condition Intervention Phase
Alzheimer's Disease
Drug: doxycycline
Drug: rifampicin
Drug: Placebo matched to doxycycline
Drug: Placebo matched to Rifampin
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Treatment With Doxycycline and Rifampicin on Biomarkers of Alzheimer's Disease in the Cerebrospinal Fluid

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • Clinical Dementia Rating scale [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Standardized Alzheimer's disease Assessment Scale -cognitive subscale [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: February 2007
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 AD combined doxycycline + rifampin
Doxycycline 100 mg b.i.d. plus rifampin 300 mg o.d. for 12 months.
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)
Other Names:
  • Rofact
  • Rifadin
Experimental: 2 AD Doxycycline only
Doxycycline 100 mg b.i.d. plus placebo matched to rifampin o.d. for 12 months.
Drug: doxycycline
capsule, 100 mg, b.i.d., daily for 1 year
Drug: Placebo matched to Rifampin
Rifampin-matched - red capsule, o.d., daily for 11 months starting at month 2.
Experimental: 3 Rifampin only
Rifampin 300 mg o.d. plus placebo matched to doxycycline b.i.d. for 12 months.
Drug: rifampicin
capsule, 300mg, o.d., daily for 11 months (administration starts in 2nd month of trial)
Other Names:
  • Rofact
  • Rifadin
Drug: Placebo matched to doxycycline
Doxycycline-matched - blue capsule, b.i.d.,daily for 12 months
Placebo Comparator: 4 Double Placebo
Placebo matched to Doxycycline b.i.d. plus placebo matched to rifampin o.d. for 12 months.
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.

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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00439166

Locations
Canada, Ontario
St.Peter's Hospital
Hamilton, Ontario, Canada, L8M1W9
Sponsors and Collaborators
Hamilton Health Sciences Corporation
The Physicians' Services Incorporated Foundation
Investigators
Study Chair: William Molloy, MB, FRCPC McMaster University
Principal Investigator: Tricia KW Woo, MD, FRCPC McMaster University
Principal Investigator: David D Cowan, MD, FRCPC McMaster University
Principal Investigator: Brandon M Kucher, PhD McMaster University
Principal Investigator: Alwin Cunje, MD, PhD University of Ottawa
  More Information

No publications provided

Responsible Party: Dr. David Cowan, McMaster University
ClinicalTrials.gov Identifier: NCT00439166     History of Changes
Other Study ID Numbers: PSI 06-47
Study First Received: February 20, 2007
Last Updated: July 27, 2010
Health Authority: Canada: Health Canada

Keywords provided by McMaster University:
doxycycline
rifampicin
cerebrospinal fluid
biomarkers
beta amyloid
tau

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Doxycycline
Doxycycline hyclate
Rifampin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014