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

NCT04685590 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB00067429
• Study Type: interventional
• Target: 48
• Locations: 2 countries
• Sites: 5

Brief 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

Conditions

Alzheimer Disease, Early Onset; Mild Cognitive Impairment

Keywords

amnestic mild cognitive impairment; Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to Week 48

Secondary Outcomes (7)

• Change in cellular senescence blood marker Senescence-Associated Secretory Phenotype (SASP) composite score

  Baseline to Week 12

• Change in cellular senescence blood marker Cluster of Differentiation 3 (CD3) in blood

  Baseline to Week 12

• Change in cellular senescence blood marker cyclin-dependent kinase inhibitor 2A (p16INK4A+) in blood

  Baseline to Week 12

• Change in cellular senescence blood marker T cells in blood

  Baseline to Week 12

• Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) slope

  Baseline to Week 48

Study Arms (2)

Treatment

EXPERIMENTAL

Dasatinib (D) is given as (1) 100mg capsule daily for 2 consecutive days (Sprycel®, Bristol Myers Squibb). Quercetin (Q) will be given as (4) 250 mg capsules daily (total 1000 mg daily) for the same 2 consecutive days (Thorne Research). Both are administered orally.

Drug: Dasatinib + Quercetin

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo Capsules

Interventions

Dasatinib + Quercetin DRUG

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.

Treatment

Placebo Capsules OTHER

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.

Placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 60 years and older at study entry
• Both sexes
• All ethnicities
• Diagnosis of amnestic mild cognitive impairment (aMCI) or early Alzheimer's disease (AD)
• Elevated tau protein as determined by CSF performed during screening. Evidence of elevated tau from previously available CSF samples will also be allowed for eligibility determination.
• 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.
• 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%.
• Prothrombin Time (PT)/Partial Thromboplastin Time (PTT)/International Normalized Ratio (INR) within normal limits.
• 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).
• 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.
• Participants must have no travel plans that would interfere with scheduling visits following consent over the 12 months of study duration.
• Must speak English fluently and have at least six years of formal education.
• Participants must be fully vaccinated against COVID-19 with the primary vaccine series per CDC recommendations, with any dose of the vaccine received at least 30 days prior to initiation of the study drug. COVID boosters are allowed during study intervention period when scheduled at least four days before or after administration of the investigational product.

You may not qualify if:

• Body mass index (BMI)\>40 kg/m2.
• Average QTcF (from 3 ECGs obtained at least one minute apart) at screening of ≥450msec in males and ≥460msec in females.
• MRI contraindications including claustrophobia, the presence of metal (ferromagnetic) implants, or cardiac pacemaker.
• Pregnancy or possible pregnancy.
• 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.
• Current or history of alcohol or substance abuse or dependence within the past 2 years per Diagnostic and Statistical Manual of Mental Disorders (DSM V criteria).
• Endorsement of current suicidality or suicidal ideation on the screening C-SSRS.
• Uncontrolled diabetes (HbA1c \> 7% or the current use of insulin or sulfonylureas).
• Poorly controlled blood pressure (systolic BP\>160, diastolic BP\>90 mmHg) based on two or more readings and as determined by the PI/study clinician.
• eGFR \< 10 ml/ min/ 1.73 m2.
• Myocardial infarction, angina, stroke, or transient ischemic attack in the past 6 months.
• Chronic heart failure.
• Presence of significant liver disease with total bilirubin \>2X upper limit.
• Inability to tolerate oral medication.
• Participants 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).

Sponsors & Collaborators

• Washington University School of Medicine: lead
• The University of Texas Health Science Center at San Antonio: collaborator
• Wake Forest University Health Sciences: collaborator

Study Sites (5)

Wake Forest Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Fundación ACE Clinical Site

Barcelona, Spain

Location

Hospital Clínic de Barcelona Site

Barcelona, Spain

Location

Sant Pau Clinical Site

Barcelona, Spain

Location

FISEVI Clinical Site

Seville, Spain

Location

Related Publications (2)

• Gonzales MM, Krishnamurthy S, Garbarino V, Daeihagh AS, Gillispie GJ, Deep G, Craft S, Orr ME. A geroscience motivated approach to treat Alzheimer's disease: Senolytics move to clinical trials. Mech Ageing Dev. 2021 Dec;200:111589. doi: 10.1016/j.mad.2021.111589. Epub 2021 Oct 21.

  PMID: 34687726 DERIVED

• Guerrero A, De Strooper B, Arancibia-Carcamo IL. Cellular senescence at the crossroads of inflammation and Alzheimer's disease. Trends Neurosci. 2021 Sep;44(9):714-727. doi: 10.1016/j.tins.2021.06.007. Epub 2021 Aug 5.

  PMID: 34366147 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

Dasatinib; Quercetin

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Flavonols; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Miranda Orr, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2020
• First Posted: December 28, 2020
• Study Start: December 22, 2021
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); ES (4)