Senolytics To Alleviate Mobility Issues and Neurological Impairment in Aging
Overview
- Phase
- Phase 1
- Intervention
- Dasatinib
- Conditions
- Aging
- Sponsor
- Lewis Lipsitz
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Neurovascular Coupling
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of this pilot study is to demonstrate the safety and feasibility of administering intermittent doses of Dasatinib and Quercetin (D+Q) in older adults at risk of Alzheimer's disease (AD). The study will evaluate whether giving D+Q may improve cerebral blood flow regulation, mobility, and cognition in older adults, and thus may prevent progression to Alzheimer's disease.
Detailed Description
The investigators will conduct a 12-week single arm, open label, pre-post pilot study in 12 adults aged 65 or older with slow gait speed (\<1.0 m/sec) and Mild Cognitive Impairment (MCI, defined as a Telephone Montreal Cognitive Assessment Score (MoCA) \<19). Participants will be asked to take 100mg of Dasatinib and 1,250mg of Quercetin for 2 consecutive days, every two weeks over a period of 12 weeks (12 doses in total, given over 6 cycles). At baseline, enrolled participants will undergo gait speed and neurocognitive testing, and provide blood and urine to evaluate biomarkers of senescence. At visits 3,4, 6, and 7, participants will have safety labs drawn, and the study team will assess medication adherence and adverse events. At visits 2, 5, and 8, participants will undergo cognitive assessments, gait speed testing, cerebral blood flow and neurovascular coupling testing. At the final study visit, participants will again provide blood and urine to assess biomarkers of senescence.
Investigators
Lewis Lipsitz
Director, Marcus Institute for Aging Research
Hebrew SeniorLife
Eligibility Criteria
Inclusion Criteria
- •Men and women \>/= 65 years
- •Ambulatory,
- •Community dwelling,
- •Slow gait speed (\<1 m/second),
- •Mild Cognitive Impairment (Telephone MoCA score \<21, which is indicative of cognitive impairment)
- •Exclusion Criteria, or as per clinical judgment:
- •Telephone MoCA score \<10 points
- •Unwilling to take study medications or follow study protocol
- •Inability to independently perform Katz Activities of Daily Living (ADLs),
- •Allergies to Dasatinib or Quercetin,
Exclusion Criteria
- Not provided
Arms & Interventions
Arm 1
Dasatinib and Quercetin
Intervention: Dasatinib
Arm 1
Dasatinib and Quercetin
Intervention: Quercetin
Outcomes
Primary Outcomes
Neurovascular Coupling
Time Frame: Screening, 8, and 14 weeks
Change in cerebral blood flow during an N-back cognitive task using transcranial doppler ultrasound.
Executive Function
Time Frame: Baseline, 8, and 14 weeks
Assess change in executive cognitive function using TRAILS test, corrected for response time. Higher scores indicate worse executive functioning.
Gait Speed
Time Frame: Baseline, 8, and 14 weeks
Assess change in gait speed. Performed without a distracting cognitive task.
Montreal Cognitive Assessment (MoCA) Score
Time Frame: Baseline, 8, and 14 weeks
The Montreal Cognitive Assessment evaluates global cognition. Scores range from 0-30 points, with higher scores indicating better cognition
Secondary Outcomes
- Physical Performance(Baseline, 8, and 14 weeks)
- Mobility(Baseline, 8, and 14 weeks)
- Grip Strength(Baseline, 8, and 14 weeks)
- Gait Speed During Cognitive Task(Baseline, 8, and 14 weeks)
- P16 ink4a Expression in CD3 Positive Cells(Screening and 14 weeks)
- SASP Factors in Blood and Urine(Screening and 14 weeks)