Senolytic Therapy to Modulate the Progression of Alzheimer's Disease (SToMP-AD) Study

• Status: Not yet recruiting
• Trial end date: 2031-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The objective of the study is to determine the safety, feasibility, and efficacy of senolytics in older adults with amnestic mild cognitive impairment (MCI) or early-stage AD (Clinical Dementia Rating (CDR)=0.5 or 1) who are tau PET positive

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Wake Forest University Health Sciences
• Collaborators: Mayo Clinic; The University of Texas Health Science Center at San Antonio
• Treatments: Dasatinib; Quercetin

Criteria

Inclusion Criteria:

1. Ages 65 years and older at screening

2. Both sexes

3. All ethnicities

4. Diagnosis of amnestic mild cognitive impairment (aMCI) or early Alzheimer's disease (AD)

5. Elevated tau protein as determined by CSF Aβ:tau ratio

6. FDA-approved medications for AD (e.g. donepezil, rivastigmine, galantamine) are permitted as long as the participant has been maintained on a stable dose for at least three months prior to study entry.

7. Labs: Normal blood cell counts, normal liver and renal function without clinically significant excursions as determined by coordinating center Medical Monitor. Total cholesterol <240 mg/dl, HbA1c ≤ 7%.

8. prothrombin time (PT)/partial thromboplastin time (PTT)/international normalized ratio (INR) within normal limits

9. Participants must have the ability to provide written consent or be accompanied by a Legally Authorized Representative designated to sign informed consent (if determined not to have decision capacity by Site PI).

10. Participants must have a study partner who agrees to participate throughout the duration of the study. The study partner must have frequent and sufficient contact (approximately 10 hours per week) with the participant and be able to provide accurate information regarding the participant's cognitive and functional abilities.

11. Participants must have no travel plans that would interfere with scheduling visits following consent over the 12 months of study duration

12. Must speak English fluently and have at least six years of formal education

Exclusion Criteria:

1. Body mass index (BMI)>40 kg/m2

2. corrected QT interval (QTc) >450 msec

3. MRI contraindications including claustrophobia, the presence of metal (ferromagnetic) implants, or cardiac pacemaker.

4. Pregnancy

5. Any significant neurologic disease other than prodromal or early AD including Parkinson's disease, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.

6. Current or history of alcohol or substance abuse or dependence within the past 2 years Diagnostic and Statistical Manual of Mental Disorders (DSM V criteria)

7. Uncontrolled diabetes (HbA1c > 7% or the current use of insulin or sulfonylureas)

8. Poorly controlled blood pressure (systolic BP>160, diastolic BP>90 mmHg)

9. eGFR < 10 ml/ min/ 1.73 m2.

10. Myocardial infarction, angina, stroke, or transient ischemic attack in the past 6 months.

11. Chronic heart failure.

12. Presence of significant liver disease with total bilirubin >2X upper limit.

13. Inability to tolerate oral medication.

14. Subjects taking medications that are sensitive to substrates or substrates with a narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6 or strong inhibitors or inducers of CYP3A4 (e.g., cyclosporine, tacrolimus, or sirolimus).

15. Subjects currently taking drugs that induce cellular senescence: alkylating agents, anthracyclines, platins, other chemotherapy.

16. Subjects on therapeutic doses of anticoagulants (e.g., warfarin, heparin, low molecular weight heparin, factor Xa inhibitors, etc.) other than low-dose aspirin

17. Subjects taking H2 antagonists or proton pump inhibitors who are unable or unwilling to reduce or hold therapy for at least 2 days prior to and during each of the 2-day courses of Dasatinib plus quercetin dosing. Instead, subjects may use antacids prior to and during each of the 2-day courses of Dasatinib plus quercetin dosing.

18. Subjects taking the following other drugs if they cannot be held for at least 2 days before and during administration of study drug or placebo: digoxin, lithium, all statins, repaglidine, bosentan, gemfibrozil, olmesartan, enalapril, valsartan, methotrexate, corticosteroids, thyroid hormones, eluxadoline, eltrombopag, nitroglycerin, pioglitazone, glyburide, enzalutamide, ezetimibe, colchicine, imatinib, cyclosporine, tacrolimus, sirolimus, carbamazepine, flecainide, phenytoin, phenobarbital, rifampicin, theophylline, warfarin, heparin, full dose ASA, clopidogrel, celecoxib, desipramine, thioridazine, venlafaxine, tizanidine, atomoxetine, voriconazole, citalopram, diazepam, escitalopram, propranolol, clozapine, cyclobenzaprine, mexiletine, olanzapine, ondansetron, riluzole.

19. Presence of any condition that the Investigator believes would put the subject at risk or would preclude the patient from successfully completing all aspects of the trial.