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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04063124
Recruitment Status : Active, not recruiting
First Posted : August 21, 2019
Last Update Posted : July 5, 2022
Sponsor:
Collaborator:
Mayo Clinic
Information provided by (Responsible Party):
The University of Texas Health Science Center at San Antonio

Tracking Information
First Submitted Date  ICMJE August 1, 2019
First Posted Date  ICMJE August 21, 2019
Last Update Posted Date July 5, 2022
Actual Study Start Date  ICMJE February 14, 2020
Actual Primary Completion Date December 10, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 16, 2019)
  • 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)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 10, 2019)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2019)
  • Complete blood count (CBC) [ Time Frame: Change from 0 to 12 weeks ]
    Laboratory assessment of CBC
  • Comprehensive Metabolic Panel (CMP) [ Time Frame: Change from 0 to 12 weeks ]
    Laboratory assessment of CMP
  • Plasma level of Quercetin [ Time Frame: Change from 0 to 12 weeks ]
    Laboratory measure of level of Quercetin in the plasma at baseline, 3, 6, 9 and 12 weeks
  • Plasma level of Dasatanib [ Time Frame: Change from 0 to 12 weeks ]
    Laboratory measure of level of Dasatanib in the plasma baseline, 3, 6, 9 and 12 weeks
  • Six Minute Walk Distance (6MWD) [ Time Frame: Change from 0 to 12 weeks ]
    A timed 6 minute walk test record total distance covered
  • Grip Strength [ Time Frame: Change from 0 to 12 weeks ]
    A measure of grip strength using a handgrip strength test
  • Short Physical Performance Battery [ Time Frame: Change from 0 to 12 weeks ]
    A battery of short physical tests which will be performed and scored. The points will be totaled with a higher score indicating a better outcome.
  • 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.
  • Wechsler lV Memory Scale [ Time Frame: Change from 0 to 12 weeks ]
    A test designed to measure memory function using a scale for scoring.
  • Benson Figure [ Time Frame: Change from 0 to 12 weeks ]
    A test to assess a subjects visuoconstructional and visual memory functions by memorizing and then drawing a figure. Scoring is out of 17 points with up to 2 points awarded for each element drawn accurately and placed correctly for 8 elements, with one potential bonus point. The total possible score is 17 with a higher score representing better memory.
  • California Verbal Learning Test II Short Form [ Time Frame: Change from 0 to 12 weeks ]
    A test of learning and memory where a list of 12 words is repeated at intervals to test recall. Each word recalled is scored 1 point and a total recall score for 3 trials used to give a total. The score obtained is compared to a normative table.
  • Clinical Global Impressions - Improvement Scale (CGI-I) [ Time Frame: 0 to 12 weeks ]
    A rating scale used to assess how much the subjects symptoms have improved or worsened using a 7 point scale:
    1. Very much improved
    2. Much improved
    3. Minimally improved
    4. No change
    5. Minimally worse
    6. Much worse
    7. Very much worse
  • Lawton's Instrumental Activities of Daily Living Scale [ Time Frame: Change from 0 to 12 weeks ]
    A questionnaire with 8 items that are rated with a summary score from 0 (low functioning) to 8 (high functioning)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Senolytic Therapy to Modulate Progression of Alzheimer's Disease
Official Title  ICMJE Pilot Study to Investigate the Safety and Feasibility of Senolytic Therapy to Modulate Progression of Alzheimer's Disease (SToMP-AD)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer Disease
Intervention  ICMJE Drug: Dasatinib + Quercetin
Intermittent D+Q administered for 2 days on/14 days off for 12 weeks (6 cycles)
Other Name: D+Q
Study Arms  ICMJE 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.
Intervention: Drug: Dasatinib + Quercetin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 16, 2019)
5
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Actual Primary Completion Date December 10, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 65 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04063124
Other Study ID Numbers  ICMJE HSC20190222H
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: All IPD that underlie results in a publication
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: At study completion
Access Criteria: Through journal publication
Current Responsible Party The University of Texas Health Science Center at San Antonio
Original Responsible Party Same as current
Current Study Sponsor  ICMJE The University of Texas Health Science Center at San Antonio
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Mayo Clinic
Investigators  ICMJE
Principal Investigator: Nicolas Musi, MD UT Health San Antonio
PRS Account The University of Texas Health Science Center at San Antonio
Verification Date June 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP