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Introduction JTR-161 is a novel allogeneic human cell product consisting of dental pulp stem cells isolated from the extracted teeth of healthy adults. It is currently under development as a cell-based therapy for ischaemic stroke. The aim of this study is to evaluate the safety and efficacy of JTR-161 in patients with acute ischaemic stroke when given as a single intravenous administration within 48 hours of symptom onset.Methods and analysis This is a first-in-human, randomised, double-blind, placebo-controlled, multicentre, phase 1/2 clinical trial to be conducted in Japan (from January 2019 to July 2021). Patients with a clinical diagnosis of anterior circulation ischaemic stroke with a National Institutes of Health Stroke Scale (NIHSS）score of 5–20 at baseline were enrolled. Patients previously treated with recombinant tissue-type plasminogen activator and/or endovascular thrombectomy were allowed to be enrolled. The study consists of three cohorts: cohorts 1 and 2 (each eight patients) and cohort 3 (60 patients). Subjects were randomly assigned to receive either JTR-161 or placebo in a 3:1 ratio in cohorts 1 and 2, and in a 1:1 ratio in cohort 3. The number of cells administered was increased sequentially from 1×108 (cohort 1) to 3 x 108 (cohort 2). In cohort 3, the higher tolerated dose among the two cohorts was administered. The primary endpoint is the proportion of patients who achieve an excellent outcome as defined by all of the following criteria at day 91 in cohort 3: modified Rankin Scale ≤1, NIHSS ≤1 and Barthel Index ≥95.Ethics and dissemination The protocol and informed consent form were approved by the institutional review board at each participating study site. A manuscript with the results of the primary study will be published in a peer-reviewed journal.Trial registration number NCT04608838; JapicCTI-194570 and Clinical Trials. gov.

BACKGROUND: Clinical-diffusion mismatch (CDM) between stroke severity and volume of diffusion-weighted imaging (DWI) lesions seems to predict penumbra. The Alberta Stroke Program Early CT Score on DWI (DWI ASPECTS) is a simple score for identifying ischaemic lesions. The authors examined whether CDM using DWI ASPECTS can predict neurological improvement in patients with acute stroke treated with intravenous tissue plasminogen activator (t-PA). METHODS: The authors enrolled consecutive patients with anterior circulation stroke treated with intravenous t-PA. The authors calculated a cut-off value for CDM using DWI ASPECTS. After excluding a group of patients with mild symptoms (National Institutes of Health Stroke Scale (NIHSS) score <8), the authors divided the patients into two groups by presence or not of CDM (a positive group (P-CDM) and a negative group (N-CDM)). The authors then compared clinical characteristics including NIHSS score and modified Rankin Scale at 90 days after intravenous t-PA. RESULTS: Seventy-one patients (male 41, mean age 74 years) were enrolled. DWI ASPECTS was linearly related to DWI lesion volume. The authors defined CDM as NIHSS scores ≥8 and DWI ASPECTS ≥7. The P-CDM group had 35 patients (61%) and the N-CDM group 22 patients (39%). NIHSS scores on admission were 15 (median) in P-CDM and 20 in N-CDM (p=0.004). NIHSS scores after intravenous t-PA improved in P-CDM but were unchanged in N-CDM (7 vs 20 at 7 days, p=0.033 on ANOVA). A favourable outcome at 90 days, defined as modified Rankin scale 0–3, was found in 46% of P-CDM patients and 14% of N-CDM patients (p=0.020). CONCLUSION: CDM determined using DWI ASPECTS may be associated with neurological improvement in patients treated with intravenous t-PA. [ABSTRACT FROM AUTHOR]