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ALSENLITE: Senolytics for Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04785300
Recruitment Status : Enrolling by invitation
First Posted : March 5, 2021
Last Update Posted : October 6, 2021
Sponsor:
Information provided by (Responsible Party):
James L. Kirkland, MD, PhD, Mayo Clinic

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
Mild Cognitive Impairment Alzheimer Disease Drug: Dasatinib Drug: Quercetin 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Study Start Date : October 2021
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Safety and Tolerability of 11 week of intermittent D+Q treatment [ Time Frame: 11 weeks ]
    Number of participants to experience adverse events/serious adverse events and hypersensitivity reactions.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04785300


Locations
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United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
James L. Kirkland, MD, PhD
Investigators
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Principal Investigator: Ronald C Petersen, MD, PhD Mayo Clinic
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: James L. Kirkland, MD, PhD, Regulatory Sponsor, Mayo Clinic
ClinicalTrials.gov Identifier: NCT04785300    
Other Study ID Numbers: 19-003394
First Posted: March 5, 2021    Key Record Dates
Last Update Posted: October 6, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Alzheimer Disease
Cognitive Dysfunction
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Dasatinib
Quercetin
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antioxidants
Protective Agents
Physiological Effects of Drugs