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

NCT ID: NCT03752294

Last Updated: 2025-04-17

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-31
• Study Completion Date: 2022-05-31

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.

Detailed Description

The study will be conducted in 2-phases. The Phase I double-blind portion of the study consists of 40-60 active participants with MCI probably due to AD and mild AD randomized to 150mg once-a-day dose of dabigatran or placebo. A futility analysis will be conducted based on month 3 plasma biomarker changes from baseline. Excluding futility, at the end of Phase I, the study continues onto the open-label phase of the study where the placebo arm will be treated with 150mg once-a-day with dabigatran from months 10-21. The active treatment arm will continue on dabigatran through month-21. For final analysis, a difference in intercept of a generalized growth model between randomization groups during Phase 2 in the Cognitive Dementia Rating Scale-Sum of Boxes (CDR-SB) will be taken as evidence of effectiveness and justify further study. All patients will discontinue dabigatran after month 21 and a 3-month follow-up period will confirm whether or not the proposed cognitive effects can be sustained in the absence of treatment. The relationships between changes in levels of plasma biomarkers over time will be tested with regards to each other and relative to MRI and cognitive testing performed at scheduled intervals.

Conditions

Mild Cognitive Impairment; Mild Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dabigatran

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

Group Type: ACTIVE_COMPARATOR

Dabigatran

Intervention Type: 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.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo - Cap

Intervention Type: 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

Open Label

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

Group Type: ACTIVE_COMPARATOR

Dabigatran

Intervention Type: 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.

Interventions

Dabigatran

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.

Intervention Type: DRUG

Placebo - Cap

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

Intervention Type: DRUG

Other Intervention Names

Pradaxa; Study Drug

Eligibility Criteria

Inclusion Criteria

1. 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

2. English speaking men & woman age 50 -85 years (inclusive)

3. Ability to provide informed consent

4. MMSE score >20 at screening

5. Informant or caregiver (e.g. family member, friend) willing to participate in semi-structured interviews

6. 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.

7. CDR Scale Global Score between 0.5 and 1

8. Stable dosing (prior 3-months) of standard AD medications are allowed

9. Demonstrated willingness to comply with study visit schedule, laboratory studies, and other study procedures

Exclusion Criteria

1. Pre-menopausal women (last menstruation < 1 year prior to screening) who are not surgically sterile.

2. Creatinine clearance < 50mL/min

3. 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)

4. Cerebrovascular disease

5. Toxic, inflammatory, and metabolic disorders, all of which may require specific investigations

6. MRI Flair or T2 signal changes in the medial temporal lobe that are consistent with infectious or vascular insults

7. Sudden onset or early occurrence of the following symptoms: gait disturbances, seizures, major and prevalent behavioral changes

8. Inability to swallow pills

9. Current anticoagulant therapy

10. Conditions associated with an increased risk of bleeding (e.g. major surgery within 30-days of baseline, planned surgery or intervention during treatment period)

11. History of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding

12. Gastrointestinal hemorrhage within the past year

13. Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30-days; hemorrhagic disorder or bleeding diathesis

14. 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)

15. Recent malignancy or radiation therapy (within 6-months) and a survival rate of 3-years,

16. Active infective endocarditis

17. Active liver disease (including but not limited to persistent ALT, AST, Alk Phos greater than twice the upper limit of the normal range; active hepatitis C (positive HCV RNA)

18. Active hepatitis B (HBs antigen +, anti HBc IgM +), active hepatitis A

19. HIV/AIDS diagnosis

MRI exclusionary criteria

1. Brain Aneurysm Clip

2. Implanted neural stimulator

3. Implanted cardiac pacemaker or defibrillator

4. Cochlear implant

5. Ocular foreign body (e.g. metal shavings)

6. Other implanted medical devices: (e.g. Swan Ganz catheter, mechanical prosthetic heart)

7. Insulin pump

8. Metal shrapnel or bullet

Additional concomitant drug exclusionary criteria will be applied by investigator.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alzheimer's Drug Discovery Foundation

OTHER

Sponsor Role: collaborator

Boehringer Ingelheim

INDUSTRY

Sponsor Role: collaborator

University of Rhode Island

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paula Grammas, PhD

Role: STUDY_DIRECTOR

Executive Director of the Ryan Institute for Neuroscience

John Stoukides, MD

Role: PRINCIPAL_INVESTIGATOR

Medical Director, Rhode Island Mood & Memory Research Institute

Other Identifiers

RIN001-001

Identifier Type: -

Identifier Source: org_study_id