ALSENLITE: Senolytics for Alzheimer's Disease

Sponsor
James L. Kirkland, MD, PhD (Other)
Overall Status
Enrolling by invitation
CT.gov ID
NCT04785300
Collaborator
(none)
20
1
1
17
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Study Details

Study Description

Brief Summary

This study is being done to evaluate the safety and feasibility of using Dasatinib and Quercetin together in subjects with Mild Cognitive Impairment (MCI) or Alzheimer's disease.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

The underlying processes driving chronic neurodegeneration in Alzheimer's disease (AD) and related neurodegenerative disorders are largely unknown. Aging is the major risk factor for AD. Moreover, individuals with AD suffer from significantly more co-morbid conditions than demographically matched older adults. This study is an open-label pilot study of intermittent administration of the senolytic drug regimen Dasatinib (D) + Quercetin (Q) in symptomatic adults over 55 with clinical diagnosis of probable Alzheimer's Disease and Alzheimer's biomarker positivity by tau-PET.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
20 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
ALSENLITE: An Open-Label Pilot Study of Senolytics for Alzheimer's Disease
Anticipated Study Start Date :
Jul 1, 2022
Anticipated Primary Completion Date :
Dec 1, 2023
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dasatinib plus Quercetin Treatment Goup

Subjects with MCI or Alzheimer's disease will take Dasatinib and Quercetin by mouth at the same times for 2 days out of every 15 days for 6 cycles lasting for a total of 77 days (12 concurrent doses of each agent).

Drug: Dasatinib
100 mg capsule daily for 2 consecutive days administered orally every 15 days (2 days on drug, 13 days off) for 6 cycles

Drug: Quercetin
Four 250 capsules once daily (total daily dosage 1000 mg) administered orally for 2 consecutive days every 15 days (2 days on drug, 13 days off) for 6 cycles

Outcome Measures

Primary Outcome Measures

  1. Safety and Tolerability of 11 week of intermittent D+Q treatment [11 weeks]

    Number of participants to experience adverse events/serious adverse events and hypersensitivity reactions.

Eligibility Criteria

Criteria

Ages Eligible for Study:
55 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Mayo Clinic in Rochester Rochester Minnesota United States 55905

Sponsors and Collaborators

  • James L. Kirkland, MD, PhD

Investigators

  • Principal Investigator: Ronald C Petersen, MD, PhD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
James L. Kirkland, MD, PhD, Regulatory Sponsor, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT04785300
Other Study ID Numbers:
  • 19-003394
First Posted:
Mar 5, 2021
Last Update Posted:
Jul 6, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 6, 2022