Wharton’s jelly derived allogeneic mesenchymal stromal cells for treatment of type 1 diabetes: Study protocol for a double-blinded, randomized, parallel, placebo-controlled trial

Abstract

Background and objectives: The Wharton’s jelly of the umbilical cord tissue contains a high density of mesenchymal stromal cells (MSCs). Wharton’s jelly derived mesenchymal stromal cells have immunosuppressive potential that can be utilized for treatment of autoimmune diseases such as type 1 diabetes (T1D). The objectives of this study are to assess the safety and efficacy of allogeneic Wharton’s Jelly derived MSCs (WJMSCs) in the treatment of T1D from the viewpoints of changes in beta-cell function, metabolic control, and diabetes treatment satisfaction during one year study period. Design: A two stage design. An open, non-randomized, dose-escalation scheme will be used in the first stage of the study, and a randomized, double-blinded, parallel, placebo-controlled scheme in the second stage of the study. Methods: The study population will consist of adult patients with T1D for Outcome measures: The primary outcome measure of this study will be safety. The secondary outcome measure will be efficacy of treatment, i.e., preservation of endogenous insulin production. This will be evaluated as delta change in C-peptide concentration in response to a mixed meal tolerance test, compared with before treatment. Discussion: By combining the first part (dose-escalation scheme) with the second part (double-blinded, parallel, placebo-controlled scheme), this study will provide both safety and efficacy data for the use of WJMSCs in the treatment of T1D. Obtained findings will guide on how to pursue this concept and indicate what dose of cells will be optimal for future trials. Ethics and dissemination: This study protocol was approved by the Ethics Committee Stockholm (approval number: 2017/1533-31/2) and the Swedish Medicinal Product Agency (EudraCT number: 2017-002766-50), and will be performed in accordance with the Declaration of Helsinki. Dissemination plans include presentations at scientific conferences and scientific publications. Patient recruitment was initiated in January 2018, and the first stage of the trial, the dose escalation, is expected to be completed for 1-month follow-up safety data, in the fourth quarter of 2018. Primary outcome measure will be estimated in 2020. Trial registration: ClinicalTrials.gov identifier: NCT03406585.