Dasatinib + Quercetin for Premature Aging in Mental Illness

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, dasatinib and quercetin, to determine if they can slow aging in individuals with mental illnesses such as depression or schizophrenia. Researchers believe these drugs help clear out old, damaged cells that contribute to aging. The trial seeks individuals over 50 with depression resistant to usual treatments or schizophrenia, who also have conditions like high blood pressure, diabetes, or arthritis. Participants should not have dementia and must be on medication for their mental illness. The goal is to understand if these drugs can improve aging-related health issues in this group. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the combination of dasatinib and quercetin is well-tolerated. In one study, older adults at risk for Alzheimer's disease received this treatment, which proved safe without major side effects. Another study examined individuals with mental health conditions like schizophrenia and assessed the safety of dasatinib and quercetin. It found no significant improvements in cognitive skills, but the treatment did not cause major safety issues. These findings suggest that the combination is generally safe for humans, though further research is needed to confirm this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for premature aging in mental illness focus on managing symptoms rather than addressing underlying causes. But Dasatinib and Quercetin work differently, targeting senescent cells that contribute to aging. Researchers are excited about this treatment because it combines a cancer drug, Dasatinib, with Quercetin, a plant flavonoid, to clear these harmful cells. This could potentially slow down or even reverse aspects of premature aging, offering a novel approach beyond typical symptom management.

What evidence suggests that dasatinib + quercetin might be an effective treatment for premature aging in mental illness?

Research suggests that using dasatinib and quercetin together, as studied in this trial, may help slow aging and lower the risk of age-related diseases. Studies have shown that this combination can reduce senescent cells, which are old cells that have stopped dividing and can cause inflammation and aging. In older rats, dasatinib and quercetin improved learning and memory, indicating possible benefits for brain health. One study found that dasatinib can reach the brain, which is important for addressing brain-related aging issues. These findings support the idea that dasatinib and quercetin might help with early aging in mental illness. ^{1 2 3 6 7}

Who Is on the Research Team?

Eric Lenze, MD

Principal Investigator

Washington University School of Medicine, Department of Psychiatry

Are You a Good Fit for This Trial?

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

I am over 50 years old, or over 60 if my condition is depression.

Exclusion Criteria

I cannot take dasatinib or quercetin due to health reasons.

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8833137/

Combination of dasatinib and quercetin improves cognitive ... Aged rats following D+Q treatment displayed improved learning abilities and effective acquisition of spatial short- and long-term memory of a new place compared ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04946383

Safety and Effectivness of Quercetin & Dasatinib on ... There is evidence that Quercetin and Dasatinib slows cell proliferation and decelerates aging and the risk of age-related diseases. The aim of this pilot study ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12120425/

Protocol for a pilot clinical trial of the senolytic drug ... Emerging research suggests that the senolytic regimen of dasatinib+quercetin (D+Q) reduces senescent cells, potentially mitigating age-related health and ...

4. withpower.com withpower.com/trial/dasatinib-quercetin-for-premature-aging-in-mental-illness-69e8d

Dasatinib + Quercetin for Premature Aging in Mental Illness The treatment successfully penetrated the central nervous system, with dasatinib detected in cerebrospinal fluid, suggesting potential for targeting cellular ...

5. aging-us.com aging-us.com/article/205581/text

Exploring the effects of Dasatinib, Quercetin, and Fisetin on ... This study aimed to assess the effects of Dasatinib and Quercetin (DQ) senolytic treatment on DNA methylation (DNAm), epigenetic age, and immune cell subsets.

6. ctv.veeva.com ctv.veeva.com/study/dasatinib-plus-quercetin-for-accelerated-aging-in-mental-disorders

Dasatinib Plus Quercetin for Accelerated Aging in Mental ... This is a pilot study that will enroll up to 40 participants and will examine the following: test the safety and feasibility of dasatinib+ ...

7. marcusinstituteforaging.org marcusinstituteforaging.org/news/pilot-study-suggests-treatment-may-improve-cognition-older-adults-risk-alzheimers-disease

Pilot Study Suggests Treatment May Improve Cognition in ... “Our findings suggest that senolytic treatment with dasatinib and quercetin is well-tolerated in older adults at risk for Alzheimer's disease ...