Objective
The goal of this proposal is to conduct a phase 2 safety trial involving children and adolescents with T1D.
Background Rationale
Mounting evidence supports the strong influence of the intestinal environment in type 1 diabetes (T1D) development; however, few “microbiome-based” strategies are currently being tested for the prevention of T1D onset in humans. Thus, we propose a bacterial strain, Lactobacillus johnsonii N6.2, specifically selected because of its prevalence in diabetes-resistant rodents. In a rodent model of T1D, the administration of L. johnsonii N6.2 was found to prevent onset of T1D. Before this therapy can be translated into a genetically predisposed human population, several safety trials in healthy and T1D subjects are necessary. As a step in this direction, we conducted a phase 1 safety trial to examine the safety, tolerability and effects of L. johnsonii N6.2 in healthy adults. As a result of this trial, we demonstrated the safety of L. johnsonii N6.2 and identified several systemic biomarkers that can be utilized to follow the effects of L. johnsonii N6.2 consumption in healthy subjects. The results of the human study provide a solid foundation for an investigation into prevention of T1D onset with L. johnsonii N6.2 in an at-risk human population. However, before preventive studies can be performed in subjects genetically predisposed to develop T1D, a phase 2 safety trial involving children and adolescents with T1D is required.
Description of Project
Mounting evidence supports the strong influence of the intestinal environment in type 1 diabetes (T1D) development; however, few “microbiome-based” strategies are currently being tested for the prevention of T1D onset in humans. Thus, we propose a bacterial strain, Lactobacillus johnsonii N6.2, specifically selected because of its prevalence in diabetes-resistant rodents. In a rodent model of T1D, the administration of L. johnsonii N6.2 was found to prevent onset of T1D. Before this therapy can be translated into a genetically predisposed human population, several safety trials in healthy and T1D subjects are necessary. We conducted a phase 1 safety trial to examine the safety, tolerability and effects of L. johnsonii N6.2 in healthy adults. As a result of this trial, we demonstrated the safety of L. johnsonii N6.2 and identified several systemic biomarkers that can be utilized to follow the effects of L. johnsonii N6.2 consumption in healthy subjects. The goal of this proposal is to conduct a phase 2 safety trial involving children and adolescents with T1D. The results obtained will be instrumental for the design of future preventive studies in subjects genetically predisposed to develop T1D. The results of the proposed phase 2 human study will provide a solid foundation for an investigation into prevention of T1D onset by L. johnsonii N6.2 in an at-risk human population.
Anticipated Outcome
The resources invested in this phase 2 safety trial will be used to determine the safety and tolerability of Lactobacillus johnsonii N6.2 in children and adolescents with T1D.
Relevance to T1D
The results of the proposed phase 2 human study will provide a solid foundation for an investigation into prevention of T1D onset by L. johnsonii N6.2 in an at-risk human population.