Trial Outcomes & Findings for Senolytic Therapy to Modulate Progression of Alzheimer's Disease (NCT NCT04063124)

NCT ID: NCT04063124

Last Updated: 2023-03-06

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

5 participants

Primary outcome timeframe

Change from 0 to 12 weeks

Results posted on

2023-03-06

Participant Flow

Subjects that were consented and passed screening

Participant milestones

Participant milestones
Measure	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. Dasatinib + Quercetin: Intermittent D+Q administered for 2 days on/14 days off for 12 weeks (6 cycles)
Overall Study STARTED	5
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Senolytic Therapy to Modulate Progression of Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intermittent D+Q n=5 Participants 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. Dasatinib + Quercetin: Intermittent D+Q administered for 2 days on/14 days off for 12 weeks (6 cycles)
Age, Continuous	76 years STANDARD_DEVIATION 5 • n=99 Participants
Sex: Female, Male Female	2 Participants n=99 Participants
Sex: Female, Male Male	3 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants
Race (NIH/OMB) White	5 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Region of Enrollment United States	5 participants n=99 Participants
Educational level High school graduate	2 Participants n=99 Participants
Educational level Some college	1 Participants n=99 Participants
Educational level College degree or higher	2 Participants n=99 Participants

PRIMARY outcome

Timeframe: Change from 0 to 12 weeks

Population: tandem mass spectrometry

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)

Outcome measures

Outcome measures
Measure	Intermittent D+Q n=5 Participants 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. Dasatinib + Quercetin: Intermittent D+Q administered for 2 days on/14 days off for 12 weeks (6 cycles)
Brain Penetrance of Dasatinib (D)	0.27 ng/ml Standard Deviation 0.19

PRIMARY outcome

Timeframe: Change from 0 to 12 weeks

Population: tandem mass spectrometry

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

Outcome measures

Outcome measures
Measure	Intermittent D+Q n=5 Participants 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. Dasatinib + Quercetin: Intermittent D+Q administered for 2 days on/14 days off for 12 weeks (6 cycles)
Brain Penetrance of Quercetin (Q)	0 ng/ml Standard Deviation 0

SECONDARY outcome

Timeframe: Change from 0 to 12 weeks

Population: total tau assessed by Simoa HD-X analyzer

Cerebrospinal Fluid collected by lumbar puncture analyzed for level of tau proteins present in CSF

Outcome measures

Outcome measures
Measure	Intermittent D+Q n=5 Participants 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. Dasatinib + Quercetin: Intermittent D+Q administered for 2 days on/14 days off for 12 weeks (6 cycles)
Alzheimer's Disease Marker - CSF Tau	-21 pg/ml Standard Deviation 35

SECONDARY outcome

Timeframe: Change from 0 to 12 weeks

Population: Abeta 42 assessed using Simoa HD-X Analyzer

Cerebrospinal Fluid collected by lumbar puncture analyzed for level of amyloid beta proteins present in CSF

Outcome measures

Outcome measures
Measure	Intermittent D+Q n=5 Participants 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. Dasatinib + Quercetin: Intermittent D+Q administered for 2 days on/14 days off for 12 weeks (6 cycles)
Alzheimer's Disease Marker - CSF Amyloid Beta	78 pg/ml Standard Deviation 75

SECONDARY outcome

Timeframe: Change from 0 to 12 weeks

Population: Assessed using Meso-Scale Discovery platform

Laboratory measure of level of IL-6 found in CSF collected pre and post treatment

Outcome measures

Outcome measures
Measure	Intermittent D+Q n=5 Participants 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. Dasatinib + Quercetin: Intermittent D+Q administered for 2 days on/14 days off for 12 weeks (6 cycles)
Senescence Marker IL-6 in CSF	0.37 pg/ml Standard Deviation 0.20

SECONDARY outcome

Timeframe: Change from 0 to 12 weeks

Population: Data were not collected for this outcome measure

Laboratory measure of level of P16 found in CSF collected pre and post treatment

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Change from 0 to 12 weeks

Population: Data were not collected for this outcome measure

Participants walk on a pressure-sensitive walkway to capture data on gait speed

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Change from 0 to 12 weeks

Population: Change in points out of 30

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.

Outcome measures

Outcome measures
Measure	Intermittent D+Q n=5 Participants 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. Dasatinib + Quercetin: Intermittent D+Q administered for 2 days on/14 days off for 12 weeks (6 cycles)
Montreal Cognitive Assessment (MoCA)	-0.20 points Standard Deviation 2.28

Adverse Events

Intermittent D+Q

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Intermittent D+Q n=5 participants at risk 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. Dasatinib + Quercetin: Intermittent D+Q administered for 2 days on/14 days off for 12 weeks (6 cycles)
General disorders Fall	20.0% 1/5 • Number of events 1 • Baseline to 12 weeks
Gastrointestinal disorders Diarrhea	20.0% 1/5 • Number of events 1 • Baseline to 12 weeks
Renal and urinary disorders Urinary tract infection	40.0% 2/5 • Number of events 2 • Baseline to 12 weeks
Endocrine disorders Hypoglycemia	20.0% 1/5 • Number of events 1 • Baseline to 12 weeks
Renal and urinary disorders Hematuria	20.0% 1/5 • Number of events 1 • Baseline to 12 weeks
Gastrointestinal disorders Emesis	20.0% 1/5 • Number of events 1 • Baseline to 12 weeks

Additional Information

Mitzi Gonzales, PhD

UT Health San Antonio

Phone: 210-450-9047

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place