A Novel Therapeutic Target for Alzheimer's Disease in Men and Women 50-85 Years of Age.

NCT03752294 | Withdrawn Phase 1 DMC

• 1 other identifier: RIN001-001
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

A randomized-control, double-blind, multi-center, delayed-start, pilot trial evaluating the disease modifying effects of a 150mg once-a-day dose vs. placebo of dabigatran in men and women, between the ages of 50-85 years, confirmed with MCI probably due to AD and mild Alzheimer's Disease.

Conditions

Mild Cognitive Impairment; Mild Alzheimer's Disease

Keywords

MCI; Mild AD; Dabigatran

Outcome Measures

Primary Outcomes (1)

• Evaluate dabigatran efficacy in MCI and mild AD population using changes in targeted plasma and CSF biomarker levels at 9 and 21 months

  Evaluate effectiveness of dabigatran (150mg daily) on disease modification measured by changes in targeted plasma and CSF biomarkers associated with the early stages of Alzheimer's disease

  9 and 21-months

Secondary Outcomes (4)

• Demonstrate a reduction in decline of cognitive function related to physical functioning in placebo arm after crossing over to 12-months of active treatment

  12 - 24 months

• Changes in cognitive performance in placebo arm after cross-over to open-label treatment phase

  24-months

• Safety and tolerability of dabigatran in experimental population (MCI and mild AD populations) based on reported serious and adverse events

  21-months

• Evaluation of cognitive performance in placebo arm after cross-over to open-label treatment phase

  24-months

Study Arms (3)

Dabigatran

ACTIVE COMPARATOR

Participants will receive 150mg dabigatran daily for a total of 9-months.

Drug: Dabigatran

Placebo

PLACEBO COMPARATOR

Participants will receive placebo daily for a total of 9-months.

Drug: Placebo - Cap

Open Label

ACTIVE COMPARATOR

All study participants are assigned to receive 150mg dabigatran daily for a total of 12 months (study month 9 through month 21)

Drug: Dabigatran

Interventions

Dabigatran DRUG

At the end of a 9-month randomized-control, double-blind treatment all study participants will cross-over to the 12-month open-label phase with a 3-month non-treatment follow-up.

Also known as: Pradaxa

Dabigatran; Open Label

Placebo - Cap DRUG

At the end of a 9-month randomized-control, double-blind treatment all study participants will cross-over to the 12-month open-label phase with a 3-month non-treatment follow-up

Also known as: Study Drug

Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of MCI likely due to AD or mild AD based on IWG-2 criteria for typical AD (A plus B at any stage) 2011 revised criteria
• English speaking men \& woman age 50 -85 years (inclusive)
• Ability to provide informed consent
• MMSE score \>20 at screening
• Informant or caregiver (e.g. family member, friend) willing to participate in semi-structured interviews
• CSF Aβ positive (MCI and AD) or a positive amyloid positron emission tomography (PET) scan within 6-months prior to screening using IWG-2 criteria.
• CDR Scale Global Score between 0.5 and 1
• Stable dosing (prior 3-months) of standard AD medications are allowed
• Demonstrated willingness to comply with study visit schedule, laboratory studies, and other study procedures

You may not qualify if:

• Pre-menopausal women (last menstruation \< 1 year prior to screening) who are not surgically sterile.
• Creatinine clearance \< 50mL/min
• Current psychiatric or neurological disorder that would contribute to cognitive impairment (focal neurological features early extrapyramidal signs, early hallucinations, cognitive fluctuations, non-AD dementia, major depression)
• Cerebrovascular disease
• Toxic, inflammatory, and metabolic disorders, all of which may require specific investigations
• MRI Flair or T2 signal changes in the medial temporal lobe that are consistent with infectious or vascular insults
• Sudden onset or early occurrence of the following symptoms: gait disturbances, seizures, major and prevalent behavioral changes
• Inability to swallow pills
• Current anticoagulant therapy
• Conditions associated with an increased risk of bleeding (e.g. major surgery within 30-days of baseline, planned surgery or intervention during treatment period)
• History of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding
• Gastrointestinal hemorrhage within the past year
• Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30-days; hemorrhagic disorder or bleeding diathesis
• Need for anticoagulant treatment of disorders, fibrinolytic agents within 48-hours of study baseline, uncontrolled hypertension (systolic blood pressure greater than 180mm Hg and/or diastolic blood pressure greater than 100 mm Hg)
• Recent malignancy or radiation therapy (within 6-months) and a survival rate of 3-years,

Sponsors & Collaborators

• University of Rhode Island: lead
• Alzheimer's Drug Discovery Foundation: collaborator
• Boehringer Ingelheim: collaborator

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Dabigatran; Drug Evaluation

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Development; Investigative Techniques; Evaluation Studies as Topic

Study Officials

• Paula Grammas, PhD

  Executive Director of the Ryan Institute for Neuroscience

  STUDY DIRECTOR

• John Stoukides, MD

  Medical Director, Rhode Island Mood & Memory Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The first phase of the study is 9-month, double-blind, randomized-control treatment. All participants participants will cross-over to phase II (open label) for an additional 12 months of treatment with a 3-month non-treatment follow-up
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized-control, Double-blind, Multicenter, Delayed-start, Pilot

Study Record Dates

• First Submitted: May 15, 2018
• First Posted: November 23, 2018
• Study Start: May 1, 2019
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2022
• Last Updated: April 17, 2025

Record last verified: 2025-04