Senolytic Therapy to Modulate Progression of Alzheimer's Disease

Pilot Study to Investigate the Safety and Feasibility of Senolytic Therapy to Modulate Progression of Alzheimer's Disease (SToMP-AD)

Sponsors

Lead Sponsor: The University of Texas Health Science Center at San Antonio

Collaborator: Mayo Clinic

Source The University of Texas Health Science Center at San Antonio
Brief Summary

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.

Detailed Description

Up to 40 potential candidates will be pre-screened to identify eligible men and women ages 65 years and over with a clinical diagnosis of early AD on a stable dose of cholinesterase inhibitors for at least 3 months (for example, Aricept). Eligible participants will undergo laboratory assessments of blood and urine, receive study medications over a twelve week period, and complete pre- and post-treatment testing including: an MRI for digital imaging of the brain; lumbar puncture to obtain cerebrospinal fluid; memory and thinking assessments; quality of life questionnaires; and tests of walking, balance and strength, all of which will be done for research purposes only. Participants must be accompanied by a Legally Authorized Representative and have no travel plans for 4-5 months that would interfere with study visits.

Overall Status Recruiting
Start Date 2020-02-14
Completion Date 2023-08-01
Primary Completion Date 2022-08-01
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Brain penetrance of Dasatinib (D) Change from 0 to 12 weeks
Brain penetrance of Quercetin (Q) Change from 0 to 12 weeks
Secondary Outcome
Measure Time Frame
Alzheimer's Disease marker - CSF tau Change from 0 to 12 weeks
Alzheimer's Disease marker - CSF amyloid beta Change from 0 to 12 weeks
Senescence marker IL-6 in CSF Change from 0 to 12 weeks
Senescence marker P16 in CSF Change from 0 to 12 weeks
Electronic gait mapping under single and dual-task conditions Change from 0 to 12 weeks
Montreal Cognitive Assessment (MoCA) Change from 0 to 12 weeks
Enrollment 5
Condition
Intervention

Intervention Type: Drug

Intervention Name: Dasatinib + Quercetin

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

Arm Group Label: Intermittent D+Q

Other Name: D+Q

Eligibility

Criteria:

Inclusion Criteria: 1. Age 65 years or above. 2. Clinical diagnosis of AD (MoCA 10-20 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

Gender:

All

Minimum Age:

65 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Nicolas Musi, MD Principal Investigator UT Health San Antonio
Overall Contact

Last Name: Nicolas Musi, MD

Phone: 210-617-5197

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: Investigator: Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases Nicolas Musi, MD. 210-617-5300 15197 [email protected] Nicolas Musi, MD Principal Investigator
Location Countries

United States

Verification Date

2021-06-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Intermittent D+Q

Type: Experimental

Description: 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.

Acronym SToMP-AD
Patient Data Yes
Study Design Info

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)

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