Senolytics dasatinib and quercetin in metabolic dysfunction-associated steatohepatitis: a proof-of-principle randomized, controlled trial

Koning M, Meijnikman AS

1. 01

   Primary endpoint (>=1-stage fibrosis improvement without worsening): 8/17 (47%) D+Q vs 1/14 (7%) placebo, P=0.021; RR 6.59 (95% CI 0.93-46.5)

2. 02

   MASH resolution 53% vs 7% (P=0.02); sensitivity analysis counting missing biopsies unfavourably P=0.068

3. 03

   snRNA-seq: lower SenMayo senescence and fibrosis gene sets on D+Q (pooled samples; senescent cells not directly counted)

4. 04

   FIB-4, NFS, ProC3, ELF and ultrasound stiffness showed no significant difference

5. 05

   Adverse events 82% vs 43% (P=0.03); lower platelets on D+Q

Study Design

Clinical Trial

Sample Size

31 subjects

Study Duration

21 weeks

Methodology

Double-blind, placebo-controlled phase 2 RCT; 21 weeks, 3 days/week x 3 weeks on / 4 weeks off, repeated 3 times; Amsterdam UMC

Limitations

Small single-centre trial (n=31, 27 completed); baseline imbalance (T2D 13/17 vs 5/14; stage 3 11/17 vs 4/14); few responders; biopsy-only surrogate endpoint; RR CI crosses 1; no hard outcomes. Some authors hold senolytic patent interests (Mayo Clinic).