Background and Objectives: Potential participants in clinical research must receive understandable and readable information in order to exercise their free will. The information letter (standard IL) imposed by French Health research authorities provide information that is difficult to understand and not adapted to participants with low health literacy (HL) level. We aimed to adapt the standard IL to participants with low HL level while respecting the regulatory requirements of clinical research. Methods: A group of experts comprising researchers, members of institutional review boards (IRB), lawyers and patients were invited to participate in a “Delphi” consensus methodology. Three rounds were planned. We proposed to the experts to rate on understandability and conformity to regulatory requirement the standard IL and 2 simplified IL developed based on adapted communication guidelines: (1) Haute Autorité de Santé, (2) Santé Publique France and (3) “Facile à Lire et à Comprendre”. The level of readability of each proposed letter has been evaluated by two readability analyzers (Scolarius and Translated Labs). In each rounds the IL were evaluated by the experts in an iterative process via an online questionnaire. Results: A total of 22 experts participated in the Delphi study group and a consensus was reached at the 3rd round on a simplified version of the IL. According to Scolarius, the standard IL had a university readability level and the final IL had a secondary readability level. The main adaptations concerned: the length of sentences, the creation of a glossary of research actors, the use of pictograms, the simplification of regulatory parts. Conclusions: This new model of the IL will enable low HL participants to better understand information and could be generalized to every patient in clinical study. The final IL will be validated during a focus group with low HL patients and then presented to regulatory authorities.