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Senolytic Therapy to Modulate Progression of Alzheimer's Disease (SToMP-AD)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04063124
Recruitment Status : Not yet recruiting
First Posted : August 21, 2019
Last Update Posted : October 15, 2019
Sponsor:
Collaborator:
Mayo Clinic
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: Dasatinib + Quercetin Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study to Investigate the Safety and Feasibility of Senolytic Therapy to Modulate Progression of Alzheimer's Disease (SToMP-AD)
Estimated Study Start Date : December 2019
Estimated Primary Completion Date : August 31, 2020
Estimated Study Completion Date : December 31, 2020


Arm Intervention/treatment
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 Name: D+Q




Primary Outcome Measures :
  1. Brain penetrance of Dasatinib (D) [ Time Frame: Change from 0 to 12 weeks ]
    Cerebrospinal Fluid (CSF) collected by lumbar puncture before and after 12 weeks of treatment to determine levels of drug that reach the central nervous system will be measured by high performance liquid chromatography/mass spectrometry (HPLC/MS)

  2. Brain penetrance of Quercetin (Q) [ Time Frame: Change from 0 to 12 weeks ]
    CSF collected by lumbar puncture before and after 12 weeks of treatment to determine levels of drug that reach the central nervous system using HPLC/MS


Secondary Outcome Measures :
  1. Alzheimer's Disease marker - CSF tau [ Time Frame: Change from 0 to 12 weeks ]
    Cerebrospinal Fluid collected by lumbar puncture analyzed for level of tau proteins present in CSF

  2. Alzheimer's Disease marker - CSF amyloid beta [ Time Frame: Change from 0 to 12 weeks ]
    Cerebrospinal Fluid collected by lumbar puncture analyzed for level of amyloid beta proteins present in CSF

  3. Senescence marker IL-6 in CSF [ Time Frame: Change from 0 to 12 weeks ]
    Laboratory measure of level of IL-6 found in CSF collected pre and post treatment

  4. Senescence marker P16 in CSF [ Time Frame: Change from 0 to 12 weeks ]
    Laboratory measure of level of P16 found in CSF collected pre and post treatment

  5. Electronic gait mapping under single and dual-task conditions [ Time Frame: Change from 0 to 12 weeks ]
    Participants walk on a pressure-sensitive walkway to capture data on gait speed

  6. Montreal Cognitive Assessment (MoCA) [ Time Frame: Change from 0 to 12 weeks ]
    A test which scores the participant with score ranges between 0 and 30. A score of 26 or over is considered normal. Individuals with mild cognitive impairment score lower and individuals with Alzheimer's disease score even lower.



Information from the National Library of Medicine

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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT04063124


Contacts
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Contact: Nicolas Musi, MD 210-617-5197 musi@uthscsa.edu
Contact: LAURI CHE KELLY, BSN 2108827117 lc_kelly@sbcglobal.net

Locations
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United States, Texas
Audie L. Murphy VA Hospital, STVHCS
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
Mayo Clinic
Investigators
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Principal Investigator: Nicolas Musi, MD UT Health San Antonio

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Responsible Party: The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT04063124     History of Changes
Other Study ID Numbers: HSC20190222H
First Posted: August 21, 2019    Key Record Dates
Last Update Posted: October 15, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The University of Texas Health Science Center at San Antonio:
Dementia
Alzheimer
Cognitive decline
dasatinib
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Dasatinib
Quercetin
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antioxidants
Protective Agents
Physiological Effects of Drugs