ALSENLITE: Senolytics for Alzheimer's Disease

Overview

About this study

The purpose of this study is to measure target engagement in cerebrospinal fluid (CSF) and blood, and to establish the feasibility and safety of Dasatinib plus Quercetin treatment in adults with early stage but symptomatic Alzheimer's Disease (AD) to inform and select the best blood, CSF, urine, and other analyses to conduct in banked samples from a larger Phase 2b clinical trial.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

1. Men and women of age 55 years and older at the time of enrollment

2. Clinical diagnosis of symptomatic probable AD (MMSE 26 to 15 or Short Test of Mental
Status 31 to 15 inclusive and/or Clinical Dementia Rating Scale/CDR = 0.5 to 2,
inclusive)

3. Not on cholinesterase inhibitors or memantine; or if on cholinesterase inhibitors
and/or memantine, on a stable dose for at least three months

4. Body Mass Index (BMI) within range of 19 - 50 kg/ m2

5. Participants must be accompanied by a LAR designated to sign informed consent and to
provide study partner reported outcomes at all visits

6. Participants must have no plans to travel over the ~3 months between Visits 3 and 14
that interfere with study visits

7. Tau positivity by brain PET imaging

8. Adequate blood counts i.e. platelets > 50,000 per microliter; HB > 9/dL, and ANC >
1000 per microliter

9. Availability and consent from a LAR.

Exclusion Criteria:

1. Unwilling or unable to give informed consent

2. Pregnancy

3. QTc > 450 msec on baseline ECG

4. MRI contraindications

5. Presence of uncontrolled psychiatric disorder (as per clinical judgment)

6. Presence of uncontrolled systemic lupus erythematosus (as per clinical judgment)

7. Substance or alcohol abuse (current alcohol use > 3 alcoholic beverage/day or > 21 per
week and as per clinical judgment)

8. Hearing, vision, or motor deficits despite corrective devices (as per clinical
judgment)

9. Myocardial infarction, angina, stroke, or transient ischemic attack in the past 6
months

10. Chronic heart failure (as per clinical judgment)

11. Neurologic, musculoskeletal, or other condition that limits subject's ability to
complete study physical assessments (as per clinical judgment)

12. Positive SARS-CoV-2 test within 30 days prior to enrollment

13. AST/ALT > 2.5x upper limit normal

14. Presence of significant liver disease with total bilirubin > 2X upper limit or as per
clinical judgment

15. Inability to tolerate oral medication (as per clinical judgment)

16. Abnormality in any of the screening laboratory studies (see section 6.21.2) or as per
clinical judgment

17. Malabsorption (as per clinical judgment)

18. Known human immunodeficiency virus infection (as per clinical judgment)

19. Known active hepatitis B or C infection

20. Invasive fungal or viral infection (as per clinical judgment)

21. Known hypersensitivity or allergy to D or Q

22. Uncontrolled pleural/pericardial effusions or ascites (as per clinical judgment)

23. New/active invasive cancer except non-melanoma skin cancers

24. Inability to tolerate oral medications (as per clinical judgment)

25. Currently taking AND unable to safely hold any of the medications listed in Appendix 1
during the days IP is administered and for 36 hours after IP administration.

26. Uncontrolled diabetes (defined as HbA1c > 7% or as per clinical judgment).

27. Gastric bypass/reduction

28. Crohn's disease

29. Myopathies (increased or low calcium, vitamin D deficiency, elevated creatine kinase
or ESR) (as per clinical judgment)

30. eGFR < 10 ml/ min/ 1.73 m2

31. Creatinine clearance < 60 mL/min/1.73 m2

32. Subjects on therapeutic doses of anticoagulants (e.g., warfarin, heparin, low
molecular weight heparin, factor Xa inhibitors, etc.)

33. On antiplatelet agents (e.g., full dose Aspirin, Clopidogrel etc.). Baby aspirin (81
mg), if absolutely necessary from cardiac perspective, will be allowed

34. Presence of any condition that the Investigator believes would put the subject at risk
or would preclude the patient from successfully completing all aspects of the trial

Involvement of special vulnerable populations: We will not involve special vulnerable
populations, such as fetuses, neonates, pregnant women, children, prisoners,
institutionalized individuals, or others who may be considered vulnerable populations
except for patients with dementia. Therefore, availability and consent from a LAR is an
inclusion criterion.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 9/20/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Vijay Ramanan, M.D., Ph.D.

Open for enrollment

Contact information:

Department of Medicine - Clinical Trials Unit

(507) 266-1944

RSTDOMCTU@mayo.edu

More information

Publications

Publications are currently not available
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CLS-20533443

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