Dasatinib Plus Quercetin for Accelerated Aging in Mental Disorders

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.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Treatment Resistant Depression; Aging, Premature
• Intervention / Treatment: Drug: Dasatinib + quercetin

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Marissa Rhea; Phone Number: 314-362-3797; Email: marissa@wustl.edu
• Study Contact Backup: Name: Julia Schweiger; Phone Number: 314-362-3153; Email: schweigj@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Principal Investigator: Eric Lenze, MD
      • Contact: Julie Schweiger; Phone Number: 314-362-3153; Email: schweigj@psychiatry.wustl.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dasatinib + quercetin; open label dasatinib plus quercetin combined as a drug therapy	Drug: Dasatinib + quercetin; dasatinib 100mg / quercetin 1250mg The intervention will involve the participant taking both dasatinib and quercetin combined.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who successfully completed and safely tolerated the intervention	Test the safety and feasibility of dasatinib plus quercetin	10 weeks

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: UConn Health
• Investigators: Principal Investigator: Eric Lenze, MD, Washington University School of Medicine, Department of Psychiatry

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: April 17, 2023
• First Submitted That Met QC Criteria: April 28, 2023
• First Posted (Actual): May 1, 2023

Study Record Updates

• Last Update Posted (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: August 31, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Schizophrenia; Older Adults; Treatment Resistant Depression; Aging, Premature
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mood Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Depressive Disorder; Depression; Schizophrenia; Psychotic Disorders; Mental Disorders; Depressive Disorder, Treatment-Resistant; Aging, Premature; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protective Agents; Protein Kinase Inhibitors; Antioxidants; Dasatinib; Quercetin
• Other Study ID Numbers: 202302203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified data available upon request
• IPD Sharing Time Frame: Data will be available by request within 1 year of the final data collection.
• IPD Sharing Access Criteria: Contact study PI
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No