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

NCT00439166 | Completed Phase 3

• 1 other identifier: PSI 06-47
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer's Disease

Keywords

doxycycline; rifampicin; cerebrospinal fluid; biomarkers; beta amyloid; tau

Outcome Measures

Primary Outcomes (2)

• Clinical Dementia Rating scale

  12 months

• Standardized Alzheimer's disease Assessment Scale -cognitive subscale

  12 months

Study Arms (4)

1 AD combined doxycycline + rifampin

EXPERIMENTAL

Doxycycline 100 mg b.i.d. plus rifampin 300 mg o.d. for 12 months.

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.

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.

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.

Drug: Placebo matched to doxycycline; Drug: Placebo matched to Rifampin

Interventions

doxycycline DRUG

capsule, 100 mg, b.i.d., daily for 1 year

1 AD combined doxycycline + rifampin; 2 AD Doxycycline only

rifampicin DRUG

capsule, 300mg, o.d., daily for 11 months (administration starts in 2nd month of trial)

Also known as: Rofact, Rifadin

1 AD combined doxycycline + rifampin; 3 Rifampin only

Placebo matched to doxycycline DRUG

Doxycycline-matched - blue capsule, b.i.d.,daily for 12 months

3 Rifampin only; 4 Double Placebo

Placebo matched to Rifampin DRUG

Rifampin-matched - red capsule, o.d., daily for 11 months starting at month 2.

2 AD Doxycycline only; 4 Double Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hamilton Health Sciences Corporation: lead
• The Physicians' Services Incorporated Foundation: collaborator

Study Sites (1)

St.Peter's Hospital

Hamilton, Ontario, L8M1W9, Canada

Location

MeSH Terms

Conditions

Alzheimer Disease; Plaque, Amyloid; Pick Disease of the Brain

Interventions

Doxycycline; Rifampin

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Frontotemporal Dementia; Frontotemporal Lobar Degeneration

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds

Study Officials

• William Molloy, MB, FRCPC

  McMaster University

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

• Tim I Standish, MA

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2007
• First Posted: February 23, 2007
• Study Start: February 1, 2007
• Primary Completion: April 1, 2010
• Study Completion: December 1, 2010
• Last Updated: March 19, 2018

Record last verified: 2017-03

Locations

CA (1)