Safety and Feasibility of Dasatinib and Quercetin in Adults at Risk for Alzheimer's Disease (STAMINA)

Senolytics To Alleviate Mobility Issues and Neurological Impairment in Aging

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.

Study Overview

• Status: Completed
• Conditions: Aging
• Intervention / Treatment: Drug: Dasatinib; Drug: Quercetin

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Hebrew Senior Life

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ambulatory,
• Community dwelling,
• Slow gait speed (<1 m/second),
• Mild Cognitive Impairment (Telephone MoCA score <19, 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,
• Hospitalization within 6 months,
• Unstable coronary artery disease (myocardial infarction within 6 months or angina),
• Stroke or transient ischemic attack in the past 6 months,
• Chronic heart failure,
• Current or chronic history of liver disease,
• Neurodegenerative disease including Parkinson's disease,
• Anemia,
• Chronic renal disease,
• Drug or alcohol abuse in the last 5 years,
• QTc prolongation,
• Thrombocytopenia,
• Neutropenia,
• Prolonged prothrombin time or INR,
• Indications of current fluid retention,
• History or current diagnosis of pulmonary hypertension,
• Inability to insonate the middle cerebral artery through a temporal bone window on at least one side using transcranial Doppler ultrasound, or
• Chronic use of any of the following medications: anti-arrhythmic medications, antipsychotics, anxiolytics, anti-platelet or anti-coagulant medications other than aspirin, quinolone antibiotics, or drugs metabolized by the same liver enzymes as Quercetin or Dasatinib.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Dasatinib and Quercetin	Drug: Dasatinib; Dasatinib 100 mg for 2 consecutive days, every two weeks for 12 weeks; Other Names: Sprycel; Drug: Quercetin; Quercetin 1,250 mg for 2 consecutive days, every two weeks for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurovascular coupling	Change in cerebral blood flow during an N-back cognitive task using transcranial doppler ultrasound.	Screening, 8, and 14 weeks
Executive function	Assess change in executive cognitive function using TRAILS test, corrected for response time	Baseline, 8, and 14 weeks
Gait speed	Assess change in gait speed. Performed without a distracting cognitive task.	Screening, 8, and 14 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical performance	Assessment of overall physical function using the short physical performance battery (SPPB) scored from 0-12, based on a composite of balance, strength, and walking speed.	Baseline, 8, and 14 weeks
Mobility	Test of mobility using timed up and go test, including standing from a chair, walking, and turning.	Baseline, 8, and 14 weeks
Grip strength	Measure of grip strength using a hand dynamometer.	Baseline, 8, and 14 weeks
Gait speed during cognitive task	Measure of gait speed during a cognitive task.	Baseline, 8, and 14 weeks
Senescent CD3 cells expressing p16	Measure of the number of senescent CD3 lymphocytes in the blood.	Screening and 14 weeks
SASP factors in blood and urine	Measure of the senescence-associated biomarkers IL-1alpha picogram/mL and IL-6 picogram/mL.	Screening and 14 weeks
SASP factors in blood and urine	Measure of the senescence-associated biomarkers MMP-9 nanograms/mL and MMP-12 nanograms/mL.	Screening and 14 weeks

Collaborators and Investigators

• Sponsor: Lewis Lipsitz
• Investigators: Principal Investigator: Lewis Lipsitz, MD, Hebrew Senior Life

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2022
• Primary Completion (Actual): January 24, 2024
• Study Completion (Actual): January 24, 2024

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: June 13, 2022
• First Posted (Actual): June 21, 2022

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Senescence
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protective Agents; Protein Kinase Inhibitors; Antioxidants; Tyrosine Kinase Inhibitors; Dasatinib; Quercetin
• Other Study ID Numbers: Pro00053594

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No