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

• Status: Not yet recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Rhode Island
• Collaborators: Alzheimer's Drug Discovery Foundation; Alzheimer’s Drug Discovery Foundation; Boehringer Ingelheim
• Treatments: Dabigatran

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.