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

Aging Clinical Trial

— STAMINA  

Official title:

Senolytics To Alleviate Mobility Issues and Neurological Impairment in Aging

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05422885
• Other study ID #: Pro00053594
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 20, 2022
• Est. completion date: January 24, 2024

Study information

• Verified date: March 2024
• Source: Hebrew SeniorLife
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: January 24, 2024
• Est. primary completion date: January 24, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Aging
• Alzheimer Disease

Intervention

Drug:
• Dasatinib
Dasatinib 100 mg for 2 consecutive days, every two weeks for 12 weeks
• Quercetin
Quercetin 1,250 mg for 2 consecutive days, every two weeks for 12 weeks

Locations

Country	Name	City	State
United States	Hebrew Senior Life	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Lewis Lipsitz

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurovascular coupling	Change in cerebral blood flow during an N-back cognitive task using transcranial doppler ultrasound.	Screening, 8, and 14 weeks
Primary	Executive function	Assess change in executive cognitive function using TRAILS test, corrected for response time	Baseline, 8, and 14 weeks
Primary	Gait speed	Assess change in gait speed. Performed without a distracting cognitive task.	Screening, 8, and 14 weeks
Secondary	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
Secondary	Mobility	Test of mobility using timed up and go test, including standing from a chair, walking, and turning.	Baseline, 8, and 14 weeks
Secondary	Grip strength	Measure of grip strength using a hand dynamometer.	Baseline, 8, and 14 weeks
Secondary	Gait speed during cognitive task	Measure of gait speed during a cognitive task.	Baseline, 8, and 14 weeks
Secondary	Senescent CD3 cells expressing p16	Measure of the number of senescent CD3 lymphocytes in the blood.	Screening and 14 weeks
Secondary	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
Secondary	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