Randomized Trial of Low-dose Naproxen in Cognitively Intact Persons at Risk of Alzheimer's Dementia
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ClinicalTrials.gov Identifier: NCT02702817 |
Recruitment Status :
Completed
First Posted : March 9, 2016
Last Update Posted : August 1, 2017
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Alzheimer Disease Cognitive Decline Due to Alzheimer Disease Mild Cognitive Impairment Due to Alzheimer Disease | Drug: Naproxen Drug: Placebo | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 200 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Prevention |
Official Title: | Investigations of Naproxen Treatment Effects in Pre-clinical Alzheimer's Disease (INTREPAD) |
Actual Study Start Date : | August 1, 2012 |
Actual Primary Completion Date : | March 31, 2017 |
Actual Study Completion Date : | July 15, 2017 |

Arm | Intervention/treatment |
---|---|
Active Comparator: naproxen
naproxen sodium tablets 220 mg twice daily for two years
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Drug: Naproxen
pale blue oval tablets
Other Name: Naprosyn, Anaprox, Aleve |
Placebo Comparator: placebo
tablets identical in appearance to naproxen tablets twice daily for two years
|
Drug: Placebo
pale blue oval tablets with no active ingredients, identical in appearance to naproxen intervention
Other Name: sugar pill |
- Trajectory of composite Alzheimer Progression Score (APS) from multiple cognitive and biomarker measures of pre-clinical Alzheimer's disease [ Time Frame: Two years for primary outcome, with intent to follow participants off-treatment for two-year observational delayed washout ]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
- frequency and severity of treatment-emergent adverse events [ Time Frame: collected in real-time over two years following RZ ]classified by organ system involvement and need for treatment interruption or cessation.
- trajectory of cognitive abilities measured by global score on Repeatable Battery for Assessment of Neuropsychological Status [ Time Frame: observed at baseline, annually thereafter over two years following randomization (RZ), and two years further (delayed washout) ]global score of primary interest, although individual scale scores will be used in secondary analyses
- ratio of total and protein-bound naproxen concentrations as well as kinetics of drug accumulation and washout [ Time Frame: estimated at three months and annually thereafter for two years following RZ, with further two years delayed washout ]estimate of blood brain barrier permeability and rapidity of drug accumulation and washout in both plasma and CSF partitions
- biomarkers of inflammatory processes [ Time Frame: measured at three months and annually thereafter for two years following RZ, with further two years delayed washout ]quantitative measures of 44 different inflammatory cytokines measured in plasma, and in CSF when available
- CSF biomarkers of AD pathogenesis [ Time Frame: observed at baseline, after three months, and annually thereafter over two years following randomization (RZ), and two years thereafter off-treatment (delayed washout) ]concentrations of total tau protein, phosphorylated tau protein, Amyloid beta 1-40 and Amyloid beta 1-42, apolipoprotein E

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Ages Eligible for Study: | 55 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02702817
Canada, Quebec | |
Douglas Hospital Research Centre | |
Montreal, Quebec, Canada, H4H1R3 |
Principal Investigator: | John C S Breitner, MD, MPH | Dept of Psychiatry, McGill University Faculty of Medicine |
Responsible Party: | John C. S. Breitner, Director, Centre for Studies on Prevention of Alzheimer's Disease, Douglas Mental Health University Institute |
ClinicalTrials.gov Identifier: | NCT02702817 |
Other Study ID Numbers: |
INTREPAD |
First Posted: | March 9, 2016 Key Record Dates |
Last Update Posted: | August 1, 2017 |
Last Verified: | July 2017 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | Only de-identified data will be made available, after completion of trial including delayed washout phase. |
Supporting Materials: |
Study Protocol Informed Consent Form (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. |
Alzheimer's disease, biomarkers, cognitive decline, pre-clinical |
Alzheimer Disease Cognitive Dysfunction Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases Tauopathies Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders Cognition Disorders Naproxen |
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