Dasatinib + Quercetin for Premature Aging in Mental Illness

Overseen By Andes Daskalakis-Perez, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must be taking: Antidepressants, Antipsychotics

Must not be taking: CPY3A4 inhibitors, Chemotherapy

Disqualifiers: Dementia, Active SI, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 20

Duration: 4 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot open-label study examines the effects of a combination of dasatinib plus quercetin - two drugs that have known senolytics properties - on physiological aging in older individuals with depression or schizophrenia.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does require that you are already on an adequate dose of medication for schizophrenia/schizoaffective disorder or depression. Some medications, especially those that interact with dasatinib or quercetin, may need to be stopped.

How is the drug Dasatinib + Quercetin unique for treating premature aging in mental illness?

Dasatinib + Quercetin is unique because it targets and removes senescent cells (old or damaged cells that no longer function properly), which may help reduce inflammation and improve symptoms related to aging. This approach is novel as it addresses cellular aging directly, unlike traditional treatments that may not target the underlying cellular mechanisms. ^{1 2 3 4 5}

Research Team

Eric Lenze, MD

Principal Investigator

Washington University School of Medicine, Department of Psychiatry

Eligibility Criteria

This trial is for people aged 50+ with schizophrenia or 60+ with treatment-resistant major depression. Participants must have three aging-related conditions like hypertension, diabetes, or arthritis, and be on stable medication for their mental disorder. They can't join if they have dementia, recent severe illnesses (like heart attacks), uncontrolled health issues (high blood pressure/diabetes), certain drug interactions, or are at risk of harming themselves.

Inclusion Criteria

I have at least three age-related conditions like high blood pressure, heart or lung disease.

I have never been diagnosed with dementia.

I have major depression that hasn't improved with at least 2 treatments, or I have schizophrenia/schizoaffective disorder.

Exclusion Criteria

Active suicidal ideation such that participant could not be safely managed in an outpatient clinical trial

I cannot take dasatinib or quercetin due to health reasons.

I am not on strong CPY3A4 drugs, drugs causing cell aging, or drugs interacting with quercetin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Questionnaires and phone screen

Treatment

Participants receive dasatinib plus quercetin for 4 weeks, with lifestyle education focusing on strength, balance, and nutrition

4 weeks

Weekly visits for medication administration and lifestyle education

Monitoring

Participants undergo MRI scans and blood draws to monitor changes in neuropsychological functioning and physiological markers

10 weeks

MRI at baseline and week 10, blood draws at baseline, weeks 1, 2, 3, 4, 10, and endpoint

Follow-up

Participants are monitored for safety and effectiveness after treatment

Remaining duration of the 1-year involvement

Assessments at baseline, week 10, and study endpoint

Treatment Details

Interventions

• Dasatinib + Quercetin

Trial Overview The study tests a combination of dasatinib plus quercetin in older adults with depression or schizophrenia to see if it slows down aging. It's an open-label pilot study where everyone knows what treatment they're getting.

Participant Groups

Group I: Dasatinib + quercetin Experimental Treatment 2 Interventions

open label dasatinib plus quercetin combined as a drug therapy

Dasatinib + Quercetin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Sprycel for:

• Chronic Myelogenous Leukemia
• Acute Lymphoblastic Leukemia

Approved in European Union as Sprycel for:

• Chronic Myelogenous Leukemia
• Acute Lymphoblastic Leukemia

Approved in Canada as Phyrago for:

• Chronic Myelogenous Leukemia
• Acute Lymphoblastic Leukemia

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

UConn Health

Collaborator

Trials

218

Recruited

59,100+

Findings from Research

In a 12-week pilot study involving 5 participants with early-stage Alzheimer's disease, the combination of dasatinib and quercetin was well-tolerated, showing safety and feasibility without significant adverse effects or early discontinuations.

The treatment successfully penetrated the central nervous system, with dasatinib detected in cerebrospinal fluid, suggesting potential for targeting cellular senescence in Alzheimer's, although cognitive improvements were not observed in this small trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Senolytic therapy to modulate the progression of Alzheimer's Disease (SToMP-AD) - Outcomes from the first clinical trial of senolytic therapy for Alzheimer's disease. Gonzales, MM., Garbarino, VR., Kautz, T., et al.[2023]

The phase I clinical trial involving 5 early-stage Alzheimer's patients demonstrated that the senolytic therapy dasatinib and quercetin was well-tolerated, with no early discontinuations and confirmed CNS penetrance of dasatinib in cerebrospinal fluid.

While the treatment did not show significant cognitive improvements, it provided safety data and insights into potential senolytic effects, indicating a need for further studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial. Gonzales, MM., Garbarino, VR., Kautz, TF., et al.[2023]

The study identified six new potential senolytic compounds, including natural products like baicalein and luteolin, which may help reduce senescent cells and inflammation associated with aging.

This research utilized advanced computational methods to analyze over 40,000 molecules, marking the first proposal of these specific compounds as having senolytic activity, although further experimental validation is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural Products as a Major Source of Candidates for Potential Senolytic Compounds obtained by in silico Screening. Barrera-Vázquez, OS., Magos-Guerrero, GA., Escobar-Ramírez, JL., et al.[2023]

In a study using SAMP10 mice, which model brain aging, the combination of dasatinib and quercetin significantly improved frailty, motor, and cognitive functions compared to a control group, indicating potential benefits of senolytic therapy in aging.

SAMP10 mice exhibited greater frailty characteristics than normal aging controls (SAMR1), and the combination therapy not only reduced these frailty markers but also positively affected the senescent phenotype in the hippocampus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dasatinib plus quercetin attenuates some frailty characteristics in SAMP10 mice. Ota, H., Kodama, A.[2022]

Both senolytic treatments, ABT-263 and dasatinib + quercetin (D+Q), effectively preserved cognitive function and maintained the integrity of the blood-brain barrier in aging male rats, suggesting their potential as therapies to combat cognitive decline.

D+Q was found to influence a greater number of genes related to inflammation and synaptic function compared to ABT-263, indicating that while both treatments are beneficial, D+Q may have a broader impact on brain health and inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of peripheral cellular senescence on brain aging and cognitive decline. Budamagunta, V., Kumar, A., Rani, A., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Senolytic therapy to modulate the progression of Alzheimer's Disease (SToMP-AD) - Outcomes from the first clinical trial of senolytic therapy for Alzheimer's disease. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Natural Products as a Major Source of Candidates for Potential Senolytic Compounds obtained by in silico Screening. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Dasatinib plus quercetin attenuates some frailty characteristics in SAMP10 mice. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Effect of peripheral cellular senescence on brain aging and cognitive decline. [2023]