Randomized Trial of Low-dose Naproxen in Cognitively Intact Persons at Risk of Alzheimer's Dementia

NCT02702817 | Completed Phase 2 DMC

• 1 other identifier: INTREPAD
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Two-year double-masked trial of over-the-counter dosage of naproxen sodium vs placebo in 200 cognitively normal participants with a parental or multiplex first-degree family history Alzheimer's disease (AD) dementia. Primary outcomes are decline in cognitive function and slope of change in a summary Alzheimer Progression Score derived from serial assessment of neuroimaging, biochemical, and sensori-neural biomarker indicators of pre-clinical disease -- all believed likely to reflect progress of preclinical AD in this high risk cohort. Approximately 2/3 of participants have volunteered also for serial lumbar punctures for analysis of cerebrospinal fluid. A two-year off-treatment delayed-washout phase is planned to examine sustained treatment effects and evidence of disease modification.

Conditions

Alzheimer Disease; Cognitive Decline Due to Alzheimer Disease; Mild Cognitive Impairment Due to Alzheimer Disease

Keywords

Alzheimer's disease, biomarkers, cognitive decline, pre-clinical

Outcome Measures

Primary Outcomes (1)

• Trajectory of composite Alzheimer Progression Score (APS) from multiple cognitive and biomarker measures of pre-clinical Alzheimer's disease

  Summary score derived using latent trait Item Response Theory analyses, trajectory estimated from mixed effects models based on multiple individual markers observed at baseline, three months, 12 months, and 24 months following randomization

  Two years for primary outcome, with intent to follow participants off-treatment for two-year observational delayed washout

Secondary Outcomes (5)

• frequency and severity of treatment-emergent adverse events

  collected in real-time over two years following RZ

• trajectory of cognitive abilities measured by global score on Repeatable Battery for Assessment of Neuropsychological Status

  observed at baseline, annually thereafter over two years following randomization (RZ), and two years further (delayed washout)

• ratio of total and protein-bound naproxen concentrations as well as kinetics of drug accumulation and washout

  estimated at three months and annually thereafter for two years following RZ, with further two years delayed washout

• biomarkers of inflammatory processes

  measured at three months and annually thereafter for two years following RZ, with further two years delayed washout

• CSF biomarkers of AD pathogenesis

  observed at baseline, after three months, and annually thereafter over two years following randomization (RZ), and two years thereafter off-treatment (delayed washout)

Study Arms (2)

naproxen

ACTIVE COMPARATOR

naproxen sodium tablets 220 mg twice daily for two years

Drug: Naproxen

placebo

PLACEBO COMPARATOR

tablets identical in appearance to naproxen tablets twice daily for two years

Drug: Placebo

Interventions

Naproxen DRUG

pale blue oval tablets

Also known as: Naprosyn, Anaprox, Aleve

naproxen

Placebo DRUG

pale blue oval tablets with no active ingredients, identical in appearance to naproxen intervention

Also known as: sugar pill

placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• good physical health including normal hemoglobin and hematocrit
• history or documentation of AD dementia in at least one parent, or in two siblings
• cognitive performance without diagnosable deficit such as dementia, "mild cognitive impairment"
• must have spouse or companion able to accompany participant for clinic visits
• six or more years of formal education
• fluent in either English or French
• provision of informed consent

You may not qualify if:

• no current peptic ulcer disease
• no history of prior peptic ulcer with bleed, perforation, intestinal obstruction
• no major psychiatric disturbance
• no regular use (4 or more doses per week) of aspirin, other non-steroidal anti-inflammatory drug (NSAID), opiate or other pain medication
• no use, present or past, of acetylcholinesterase inhibitors or memantine
• no regular use of vitamin E at dosage of 600 i.u.
• no drug or alcohol dependence
• no allergy to NSAIDs or sulfa antibiotics

Sponsors & Collaborators

• Douglas Mental Health University Institute: lead
• McGill University: collaborator
• Johns Hopkins University: collaborator

Study Sites (1)

Douglas Hospital Research Centre

Montreal, Quebec, H4H1R3, Canada

Location

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

Naproxen; Sugars

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Carbohydrates

Study Officials

• John C S Breitner, MD, MPH

  Dept of Psychiatry, McGill University Faculty of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Centre for Studies on Prevention of Alzheimer's Disease

Study Record Dates

• First Submitted: December 19, 2015
• First Posted: March 9, 2016
• Study Start: August 1, 2012
• Primary Completion: March 31, 2017
• Study Completion: July 15, 2017
• Last Updated: August 1, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be available for completed trial in March, 2018. Data for delayed washout / continuation phase will be made available at biennial intervals thereafter
• Access Criteria: Qualified personnel should contact principal investigator and Study Coordinator for Data Sharing Agreement form, which must be completed and reviewed prior to release of data.

Locations

CA (1)