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
This study is a Phase II multi-site, randomized, double-blind placebo controlled trial to determine 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
48
D+Q will be administered once daily (1st dose of each cycle will be given, supervised, at the clinic visit; the 2nd dose will be taken at home) for 2 consecutive days followed by a 13-day (+/- 2 day) no-drug period for 12 consecutive weeks for 6 rounds of administration.
Matching placebo capsules following the same administration protocol as the experimental treatment - administered once daily (1st dose of each cycle will be given, supervised, at the clinic visit; the 2nd dose will be taken at home) for 2 consecutive days followed by a 13-day (+/- 2 day) no-drug period for 12 consecutive weeks for 6 rounds of administration.
Wake Forest Health Sciences
Winston-Salem, North Carolina, United States
Fundación ACE Clinical Site
Barcelona, Spain
Hospital Clínic de Barcelona Site
Barcelona, Spain
Sant Pau Clinical Site
Barcelona, Spain
Serious Adverse Events (SAEs) and Adverse Events (AEs) in treatment group as compared to placebo group
Adverse Events (AEs) and SAEs will be collected at each in-person visit and at scheduled telephone visits from baseline to week 48. Incidence of SAEs between groups (treatment vs. placebo) will be reviewed by the Data Safety Monitoring Board (DSMB) for clinical significance.
Time frame: Baseline to Week 48
Change in cellular senescence blood marker Senescence-Associated Secretory Phenotype (SASP) composite score
Composite score (average z-score of log-transformed values) of ten primary SASP factors measured in blood.
Time frame: Baseline to Week 12
Change in cellular senescence blood marker Cluster of Differentiation 3 (CD3) in blood
Primary markers of cellular senescence CD3 measured in blood.
Time frame: Baseline to Week 12
Change in cellular senescence blood marker cyclin-dependent kinase inhibitor 2A (p16INK4A+) in blood
Primary markers of cellular senescence p16INK4A+ measured in blood.
Time frame: Baseline to Week 12
Change in cellular senescence blood marker T cells in blood
Primary markers of cellular senescence T cells measured in blood.
Time frame: Baseline to Week 12
Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) slope
CDR is calculated on the basis of testing six different cognitive and behavioral domains such as memory, orientation, judgment and problem solving, community affairs, home and hobbies performance, and personal care. The CDR is based on a scale of 0-3: no dementia (CDR = 0), questionable dementia (CDR = 0.5), MCI (CDR = 1), moderate cognitive impairment (CDR = 2), and severe cognitive impairment (CDR = 3). The six domains are often summed to create a 0 - 18 "sum of the boxes" score. CDR-SB has been shown to demonstrate sensitivity to cognitive changes associated with progression of amnestic mild cognitive impairment (aMCI) and early Alzheimer's Disease (AD).
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FISEVI Clinical Site
Seville, Spain
Time frame: Baseline to Week 48
Change in the 14 - item Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog 14) slope
A psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis. A higher score indicates more impairment. Scores from the original portion of the test range from 0 (best) to 65 (worse), and are added to the mean of the words not immediately recalled (max of 10) and the number of items not recalled after a delay (ranging from 0-10) all total the maximum score of 85. A positive change indicates cognitive worsening.
Time frame: Baseline to Week 48
Change in Positron Emission Tomography (PET) - Computed Tomography (CT) - brain tau pathology
Tau levels in the brain will measured by 18F AV1451 PET imaging to assess target engagement of dasatinib and quercetin (D+Q) and impact on brain tau as a relevant Alzheimer's Disease (AD) biomarker.
Time frame: Baseline to Week 48