- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03752294
A Novel Therapeutic Target for Alzheimer's Disease in Men and Women 50-85 Years of Age.
November 20, 2018 updated by: University of Rhode Island
A 24-month, Randomized-control, Double-blind, Multi-center, Delayed-start, Pilot Study Evaluating Thrombin Inhibitions Alzheimer's Disease Using 150mg Dabigatran Daily: A Novel Therapeutic Target for Alzheimer's Disease
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.
Study Overview
Status
Unknown
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Anticipated)
40
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Chris Getter
- Phone Number: 401-874-2358
- Email: cgetter@uri.edu
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
50 years to 85 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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,
- Active infective endocarditis
- 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)
- Active hepatitis B (HBs antigen +, anti HBc IgM +), active hepatitis A
- HIV/AIDS diagnosis
MRI exclusionary criteria
- Brain Aneurysm Clip
- Implanted neural stimulator
- Implanted cardiac pacemaker or defibrillator
- Cochlear implant
- Ocular foreign body (e.g. metal shavings)
- Other implanted medical devices: (e.g. Swan Ganz catheter, mechanical prosthetic heart)
- Insulin pump
- Metal shrapnel or bullet
Additional concomitant drug exclusionary criteria will be applied by investigator.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Dabigatran
Participants will receive 150mg dabigatran daily for a total of 9-months.
|
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.
Other Names:
|
Placebo Comparator: Placebo
Participants will receive placebo daily for a total of 9-months.
|
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
Other Names:
|
Active Comparator: Open Label
All study participants are assigned to receive 150mg dabigatran daily for a total of 12 months (study month 9 through month 21)
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluate dabigatran efficacy in MCI and mild AD population using changes in targeted plasma and CSF biomarker levels at 9 and 21 months
Time Frame: 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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Demonstrate a reduction in decline of cognitive function related to physical functioning in placebo arm after crossing over to 12-months of active treatment
Time Frame: 12 - 24 months
|
Demonstrate an observed benefit of cognitive performance/function using the ADCS ADL MCI
|
12 - 24 months
|
Changes in cognitive performance in placebo arm after cross-over to open-label treatment phase
Time Frame: 24-months
|
Evaluate effectiveness of dabigatran (150mg daily) using the CDR-SB
|
24-months
|
Safety and tolerability of dabigatran in experimental population (MCI and mild AD populations) based on reported serious and adverse events
Time Frame: 21-months
|
Determine the safety and tolerability of dabigatran in MCI probably due to AD and mild AD population using physician and patient reported adverse events.
|
21-months
|
Evaluation of cognitive performance in placebo arm after cross-over to open-label treatment phase
Time Frame: 24-months
|
Evaluate effectiveness of dabigatran (150mg daily) using the MoCA
|
24-months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Paula Grammas, PhD, Executive Director of the Ryan Institute for Neuroscience
- Principal Investigator: John Stoukides, MD, Medical Director, Rhode Island Mood & Memory Research Institute
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
November 1, 2018
Primary Completion (Anticipated)
November 1, 2021
Study Completion (Anticipated)
December 1, 2021
Study Registration Dates
First Submitted
May 15, 2018
First Submitted That Met QC Criteria
November 20, 2018
First Posted (Actual)
November 23, 2018
Study Record Updates
Last Update Posted (Actual)
November 23, 2018
Last Update Submitted That Met QC Criteria
November 20, 2018
Last Verified
November 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurocognitive Disorders
- Neurodegenerative Diseases
- Dementia
- Tauopathies
- Cognition Disorders
- Alzheimer Disease
- Cognitive Dysfunction
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Protease Inhibitors
- Antithrombins
- Serine Proteinase Inhibitors
- Anticoagulants
- Dabigatran
Other Study ID Numbers
- RIN001-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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