Phase I clinical trial to evaluate TOTUM-63, a botanical complex for managing prediabetes

The IDF estimates that the number of individuals with diabetes will rise by almost 55% to 640 million by 2040. According to the ADA, 86 million Americans aged 20 years and over are prediabetic. We have developed an innovative botanical complex (BC) that aims to reverse prediabetes and to prevent each dysfunction and/or its consequences independently. The ability of the BC to control fasting glycemia, HbA1c, insulin sensitivity, serum and hepatic triglycerides, and weight gain through a specific effect on fat mass has been demonstrated in different animal models (db/db, C57BL/6 high fat diet, C57BL/6NR and Syrian hamster normal diet). Following these results, a first Phase I open trial was initiated on slightly overweight male volunteers (NCT02790489). The study included an initial period of supplementation with 2.5g/ day of the BC for 4 weeks (V1; V2:V1+4weeks) followed by an intermediary analysis and a wash-out period of 2 weeks, then 4 weeks of supplementation with 5.0g/day (V3, V2+2weeks; V4:V3+4weeks). Different safety parameters, in particular hepatic, urinary, renal and hemodynamic, were assessed at all visits. Glycemia and insulinemia were also monitored from catheter samples after taking a standardized breakfast (Breakfast Tolerance Test: BTT) at V3 and V4. Fourteen volunteers completed the trial; 1 volunteer left the study after V2 due to a persistent health problem identified on inclusion that was independent of the BC. The results do not show any clinically significant increase in the various safety parameters, objectifying the very good tolerance of the BC for the two doses tested. In addition, BC did not induce an increase in insulin secretion during the BTT. Conversely, we observed a decrease in the insulinemia AUC (V4:3286±624 versus V3:5445±1240mUI.min/L,-40%, p=0.02), and a downward trend for the glycemia AUC (V4:118±28 versus V3:168±28mmol.min/L,-30%, p=0.08). The candidate BC is currently undergoing a Phase 2a trial on 80 prediabetic subjects with abdominal obesity (NCT02868177).