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NCT04313634

Targeting Cellular Senescence With Senolytics to Improve Skeletal Health in Older Humans

Completed Phase 2 Results posted Last updated 22 July 2024
What this trial tests

Phase 2 trial testing Dasatinib in Healthy in 74 participants. Completed in 6 June 2023.

Timeline
9 June 2020
Primary endpoint
6 June 2023
6 June 2023

Quick facts

Lead sponsorSundeep Khosla, M.D.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposesupportive care
Enrollment74
Start date9 June 2020
Primary completion6 June 2023
Estimated completion6 June 2023
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Sundeep Khosla, M.D.

Who can join

60 and older, female only, with Healthy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in C-terminal Telopeptide of Type I Collagen [CTX] Primary · Baseline, 20 weeks

Percent change in serum bone turnover markers C-terminal telopeptide of type I collagen \[CTX\]. The C-terminal telopeptide (CTX), also known as carboxy-terminal collagen crosslinks, is a biomarker used to measure the rate of bone turnover. It provides valuable information for assessing bone health and evaluating treatment responses.

GroupValue95% CI
Dasatinib Plus Quercetin Treatment Goup-4.1-28.1 – 114.6
Fisetin Treatment Group13.7-42.7 – 61.0
Untreated Control Group-7.7-42.4 – 22.5
Change in Bone Turnover Markers Secondary · Baseline, 2 weeks

Percent change in amino-terminal propeptide of type I collagen (P1NP). The P1NP assay measures the serum concentration of the amino-terminal propeptide of type I procollagen (P1NP). As the concentration of this extension propeptide is directly proportional to the amount of new collagen laid down in bone, it can be used to assess bone formation.

GroupValue95% CI
Dasatinib Plus Quercetin Treatment Goup0.8-39.6 – 113.5
Fisetin Treatment Group-31.9-74.0 – 23.3
Untreated Control Group-15.2-55.0 – 59.8
Change in Bone Turnover Markers Secondary · Baseline, 4 weeks

Percent change in amino-terminal propeptide of type I collagen (P1NP). The P1NP assay measures the serum concentration of the amino-terminal propeptide of type I procollagen (P1NP). As the concentration of this extension propeptide is directly proportional to the amount of new collagen laid down in bone, it can be used to assess bone formation.

GroupValue95% CI
Dasatinib Plus Quercetin Treatment Goup4.2-61.4 – 1480
Untreated Control Group-12.1-58.0 – 95.9
Change in Bone Turnover Markers Secondary · Baseline, 20 weeks

Percent change in amino-terminal propeptide of type I collagen (P1NP). The P1NP assay measures the serum concentration of the amino-terminal propeptide of type I procollagen (P1NP). As the concentration of this extension propeptide is directly proportional to the amount of new collagen laid down in bone, it can be used to assess bone formation.

GroupValue95% CI
Dasatinib Plus Quercetin Treatment Goup-8.6-48.1 – 130.9
Fisetin Treatment Group4.5-34.8 – 29.7
Untreated Control Group0.1-49.2 – 95.2
Change in Bone Mineral Density (BMD) Secondary · Baseline, 20 weeks

Percent change in BMD by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, hip ((total and femoral neck (FN), and radius (total and ultra-distal)).

Lumbar Spine
GroupValue95% CI
Dasatinib Plus Quercetin Treatment Goup-0.2-3.1 – 6.2
Fisetin Treatment Group0-1.5 – 8.9
Untreated Control Group0.5-10.4 – 6.8
Hip (Femoral neck )
GroupValue95% CI
Dasatinib Plus Quercetin Treatment Goup-0.3-4.8 – 4.0
Fisetin Treatment Group-0.9-3.7 – 2.0
Untreated Control Group-0.5-6.0 – 19.2
Radius
GroupValue95% CI
Dasatinib Plus Quercetin Treatment Goup0.4-3.0 – 6.9
Fisetin Treatment Group0.7-12.1 – 5.7
Untreated Control Group0.2-4.7 – 12.9
Change in Plasma Senescence-associated Secretory Phenotype (SASP) Secondary · Baseline, 2 weeks

Percent change in SASP cells (representing the total senescence cell burden) present. Assessment of senescence markers in bone at baseline and 2 weeks.

GroupValue95% CI
Dasatinib Plus Quercetin Treatment Goup-2.6-187.7 – 16.4
Fisetin Treatment Group-0.9-41.8 – 3.7
Untreated Control Group-2.5-110.4 – 91.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events were collected from baseline to end of study, approximately 20 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dasatinib Plus Quercetin Treatment Goup
Serious: 0/30 (0%)
Deaths: 0/30
Fisetin Treatment Group
Serious: 1/14 (7%)
Deaths: 0/14
Untreated Control Group
Serious: 0/30 (0%)
Deaths: 0/30

Serious adverse events (1 terms)

ReactionSystemDasatinib Plus Quercetin T…Fisetin Treatment GroupUntreated Control Group
Gastric hemorrhageGastrointestinal disorders
Other adverse events (42 terms — click to expand)

ReactionSystemDasatinib Plus Quercetin T…Fisetin Treatment GroupUntreated Control Group
HeadacheNervous system disorders
DiarrheaGastrointestinal disorders
NauseaGeneral disorders
Pain in extremityMusculoskeletal and connective tissue disorders
FatigueGeneral disorders
ConstipationGastrointestinal disorders
PainGeneral disorders
Gastroesophageal reflux diseaseGastrointestinal disorders
CovidRespiratory, thoracic and mediastinal disorders
VertigoEar and labyrinth disorders
Abdominal distentionGastrointestinal disorders
Abdominal painGastrointestinal disorders
Dry MouthGastrointestinal disorders
Allergic rhinitisRespiratory, thoracic and mediastinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - otherRespiratory, thoracic and mediastinal disorders
AnorexiaMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
Metabolism and nutrition disorders - otherMetabolism and nutrition disorders
ArthritisMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
Neck painMusculoskeletal and connective tissue disorders
Cardiac disorders - otherCardiac disorders
DepressionPsychiatric disorders
InsomniaPsychiatric disorders
DizzinessNervous system disorders
Extrapyramidal disorderNervous system disorders
Muscle weaknessNervous system disorders
NeuralgiaNervous system disorders
Dry SkinSkin and subcutaneous tissue disorders
HyperhidrosisSkin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - otherSkin and subcutaneous tissue disorders
Facial painGeneral disorders
Flu like symptomsGeneral disorders
FlushingVascular disorders
Hot flashesReproductive system and breast disorders
MenorrhagiaReproductive system and breast disorders
Renal and urinary disorders - otherRenal and urinary disorders
Urinary frequencyRenal and urinary disorders
Skin infectionSkin and subcutaneous tissue disorders

Most-reported serious reactions: Gastric hemorrhage.

Data from ClinicalTrials.gov NCT04313634 adverse events section.

Sponsor's own description

To determine if senolytic drugs reduce senescent cell burden and reduce bone resorption markers/increase bone formation markers in elderly women.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Cellular senescence in ageing: from mechanisms to therapeutic opportunities.
    Di Micco R, Krizhanovsky V, Baker D, d'Adda di Fagagna F. · · 2021 · cited 1687× · PMID 33328614 · DOI 10.1038/s41580-020-00314-w
  2. Cellular senescence and senolytics: the path to the clinic.
    Chaib S, Tchkonia T, Kirkland JL. · · 2022 · cited 818× · PMID 35953721 · DOI 10.1038/s41591-022-01923-y
  3. Epigenetic regulation of aging: implications for interventions of aging and diseases.
    Wang K, Liu H, Hu Q, Wang L, et al · · 2022 · cited 406× · PMID 36336680 · DOI 10.1038/s41392-022-01211-8
  4. Therapy-Induced Senescence: Opportunities to Improve Anticancer Therapy.
    Prasanna PG, Citrin DE, Hildesheim J, Ahmed MM, et al · · 2021 · cited 264× · PMID 33792717 · DOI 10.1093/jnci/djab064
  5. Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span.
    Robbins PD, Jurk D, Khosla S, Kirkland JL, et al · · 2021 · cited 231× · PMID 32997601 · DOI 10.1146/annurev-pharmtox-050120-105018
  6. Skeletal Aging and Osteoporosis: Mechanisms and Therapeutics.
    Chandra A, Rajawat J. · · 2021 · cited 175× · PMID 33805567 · DOI 10.3390/ijms22073553
  7. Endothelial senescence in vascular diseases: current understanding and future opportunities in senotherapeutics.
    Han Y, Kim SY. · · 2023 · cited 138× · PMID 36599934 · DOI 10.1038/s12276-022-00906-w
  8. Bone Aging, Cellular Senescence, and Osteoporosis.
    Pignolo RJ, Law SF, Chandra A. · · 2021 · cited 130× · PMID 33869998 · DOI 10.1002/jbm4.10488

Verify or expand the search:

Other trials of Dasatinib

Trials testing the same drug.

Other recruiting trials for Healthy

Currently open trials in the same condition.

Other Sundeep Khosla, M.D. trials

Trials by the same sponsor.

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