Dasatinib Plus Quercetin for Accelerated Aging in Mental Disorders

Schizophrenia Clinical Trial

Official title:

Dasatinib Plus Quercetin for Accelerated Aging in Mental Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05838560
• Other study ID #: 202302203
• Status: Recruiting
• Phase: Phase 2
• Start date: July 1, 2023
• Est. completion date: May 1, 2026

Study information

• Verified date: August 2023
• Source: Washington University School of Medicine
• Contact: Marissa Rhea
• Phone: 314-362-3797
• Email: marissa[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

This is a pilot study that will enroll up to 40 participants and will examine the following:

1. test the safety and feasibility of dasatinib+quercetin in two mental illnesses associated with accelerated aging: schizophrenia and treatment-resistant depression

2. examine changes in SASP (senescence-associated secretory phenotype) with dasatinib+quercetin treatment

3. examine acute and long-term changes in neuropsychological functioning, functional status, and brain markers of aging, as well as in clinical symptoms of the illnesses (treatment-resistant depression and schizophrenia).

This study will also combine the treatment of dasatinib plus quercetin and lifestyle-based risk factor management - which will involve the research team during the medication intervention portion to provide lifestyle education focusing on strength, balance, and nutrition. The research team will maintain close contact with participants to offer encouragement, address questions and help navigate barriers to engaging in the activities.

Before study enrollment, participants will be screened using questionnaires and a phone screen prior to being consented.

The participant will be involved for about 1 year and self-administer 8 total doses of the medications - two consecutive days of dasatinib 100mg orally plus quercetin 1250mg orally on weeks 1 (ie., 2 days on, 5 days off), 2, 3, and 4.

The participant will undergo an MRI scan at baseline and approximately week 10 of the study.

Blood draws will occur at baseline, week 1, 2, 3, 4, 10, and at the endpoint. 10 ml of blood will be taken each time for 700 ml over 1 year.

Participants will have several questionnaires and assessments to complete at baseline, week 10, and the study's endpoint.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: May 1, 2026
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

1. Either major depression, which is treatment-resistant (currently depressed despite at least 2 adequate trials of antidepressants in this or the previous episode), or schizophrenia/schizoaffective disorder.

2. Age 50+ (60+ for depression).

3. Three conditions associated with aging (e.g., hypertension/diabetes/metabolic syndrome, cardiac disease, lung disease other than asthma, cancer with adult-onset, arthritis, and inflammatory diseases typically seen in aging).

4. No history of dementia by patient report.

5. Already taking an adequate dose of medication for schizophrenia/schizoaffective disorder or depression.

Exclusion Criteria:

1. Contraindications for dasatinib or quercetin

2. Active SI such that participant could not be safely managed in an outpatient clinical trial.

3. Taking medications that are strong CPY3A4 inhibitors or strong inducers, or that induce senescence (e.g., alkylating agents, anthracyclines, platins/other chemotherapy), or everolimus and topotecan (which have interactions with quercetin).

4. All medications and medical conditions will be reviewed by physician study investigators to determine whether the medication or condition, in the opinion of the investigators, makes the participant inappropriate for the study. Examples of such potential excluding conditions: Active inflammatory, infectious, or malignant disease; sensory deficits that would interfere with assessments; recent heart attack or stroke; severe bleeding disorder; uncontrolled hypertension or diabetes mellitus; active liver disease or cirrhosis; current use of systemic steroids, quinolone antibiotics, hydroxychloroquine or chloroquine.

Related Conditions & MeSH terms

• Aging, Premature
• Depression
• Depressive Disorder, Treatment-Resistant
• Mental Disorders
• Psychotic Disorders
• Schizophrenia
• Treatment Resistant Depression

Intervention

Drug:
• Dasatinib + quercetin
dasatinib 100mg / quercetin 1250mg The intervention will involve the participant taking both dasatinib and quercetin combined.

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	UConn Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants who successfully completed and safely tolerated the intervention	Test the safety and feasibility of dasatinib plus quercetin	10 weeks