Purpose

The purpose of this pilot study is to evaluate whether a combination of two drugs, dasatinib (D) and quercetin (Q) [D+Q], penetrate the brain using cerebrospinal fluid (CSF) in older adults with early Alzheimer's disease (AD). This combination of drug therapy has been shown to affect dying cells in humans with other chronic illnesses and in Alzheimer's mice models. The study team want to know if this combination of medications will reach the brain in order to evaluate if this intervention may be effective for treating AD symptoms in future studies. This is also known as a "proof of concept" study.

Category

IRB Number
20190222HU
NCT Number
NCT04063124
Open to Enrollment
Yes
Sponsor
The University of Texas Health Science Center at San Antonio -



Study Contact

Local Recruitment Point of Contact
Floyd Jones
+1 (210) 450-3158
jonesfa@uthscsa.edu

Local Recruitment Point of Contact
Amy Saklad
(210) 567-8229
saklada@uthscsa.edu

Principal Investigator
Mitzi Gonzales

Regulatory Point of Contact
Mitzi Gonzales
(210) 450-9047
gonzalesm20@uthscsa.edu

Regulatory Point of Contact
Diana Jarbeau-may
(210) 617-5390
jarbeaumay@uthscsa.edu

Regulatory Point of Contact
Floyd Jones
+1 (210) 450-3158
jonesfa@uthscsa.edu

Regulatory Point of Contact
Amy Saklad
(210) 567-8229
saklada@uthscsa.edu



Eligibility

Eligible Ages
Over 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

    1. Age 65 years or above.
    2. Clinical diagnosis of AD (MoCA 10-18 and Clinical Dementia Rating Scale/CDR = 1) on a stable dose of cholinesterase inhibitors for at least three months
    3. Body Mass Index (BMI) within range of 19 - 35 kg/ m2
    4. Labs: Normal blood cell counts without clinically significant excursions (WBCs: 4,500-10,500 cells/mcL; absolute neutrophil count: 1,800-8,700 cells/mcL; platelets: 140-450 K/uL; hemoglobin 12.0-17.5 grams/dL); liver and renal function (AST 10-40 IU/L, total bilirubin 0.1-1.4 mg/dl); cholesterol (<240 mg/dl), triglycerides (<300 mg/dl), and glucose control (HbA1c < 7%). PT/PTT/INR within normal limits
    5. Participants must be accompanied by a Legally Authorized Representative designated to sign informed consent and to provide study partner reported outcomes at all remaining visits
    6. Participants must have no plans to travel over the next 4-5 months that interfere with study visits following consent

Exclusion Criteria

    1. Hearing, vision, or motor deficits despite corrective devices;
    2. Alcohol or drug abuse;
    3. MRI contraindications;
    4. Myocardial infarction, angina, stroke or transient ischemic attack in the past 6 months; QT interval >440 on ECG will not be enrolled. Chronic heart failure will be exclusionary;
    5. Participants with coagulation disorders;
    6. Neurologic, musculoskeletal, or other condition that limits subject's ability to complete study physical assessments;
    7. Uncontrolled diabetes (HbA1c > 7% or the current use of insulin);
    8. Current or chronic history of liver disease, or known hepatic or biliary abnormalities;
    9. Use of anti-arrhythmic medications known to cause QTc prolongation, anti-platelet or anti-coagulant medication;
    10. Current use of quinolone antibiotics.
    11. Poorly controlled blood pressure (systolic BP>160, diastolic BP>90 mmHg).
    12. Active inflammatory, autoimmune, infectious, hepatic, gastrointestinal, malignant, and psychiatric disease.
    13. History of or MRI-positive for any space occupying lesion, including mass effect or abnormal intracranial pressure, which would indicate contraindication to lumbar puncture

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Intervention Model Description
This study is an open-label pilot study of intermittent D+Q to measure its target engagement in CSF and blood, and to establish the feasibility and safety of D+Q treatment in older adults with early stage AD as initial proof-of-concept for a larger Phase 2 clinical trial.
Primary Purpose
Treatment
Masking
None (Open Label)
Condition
  • Alzheimer Disease
  • Arm Groups

    ArmDescriptionIntervention
    Experimental

    Intermittent D+Q

    Senolytic treatment in 5 individuals with early AD to determine levels of drug that reach the central nervous system (CNS) by collecting cerebral spinal fluid (CSF), and begin collecting initial data on target engagement of senescent cells, AD-related markers, and AD-relevant outcomes for future trials.
  • Drug: Dasatinib + Quercetin

    Intermittent D+Q administered for 2 days on/14 days off for 12 weeks (6 cycles)

    Other names:

    • D+Q