Safety, Efficacy Evaluation of Empagliflozin Administration for Neutropenia in Glycogenosis Type 1b and G6PC3 Deficiency — GLYCO-1B  

Glycogen Storage Disease Type I Clinical Trial

Official title: Evaluation of the Safety and Efficacy of Empagliflozin Administration as a Treatment for Neutropenia in Patients With Glycogenosis Type 1b and G6PC3 Deficiency

Status Recruiting

Clinical Trial Summary

Treatment of neutropenia of G6PC3 and Glycogenosis type 1b patients with empagliflozin

Clinical Trial Description

Ubiquitous glucose-6-phosphatase deficiency (G6PC3) and glucose-6-phosphate transporter deficiency (G6PT/SLC37A4) both cause neutropenia. Studies on a G6PC3 deficient mouse model by Dr Veiga-da-Cunha and Prof. Van Schaftingen and colleagues have shown that these two proteins collaborate to hydrolyze a metabolite that exerts toxic effects on neutrophils. This metabolite is 1,5-anhydroglucitol-6-phosphate. It is formed by phosphorylation of a glucose analogue, 1,5-anhydroglucitol, which is present in the blood of all humans, mice and other mammals.

This discovery of the function of G6PC3 and G6PT opens up therapeutic prospects, in that lowering the concentration of 1,5-anhydroglucitol in the blood should reduce the concentration of 1,5-anhydroglucitol-6-phosphate in the cells and thus reduce its toxic effects. Veiga-da-Cunha, Van Schaftingen and colleagues have already shown that this is the case for a model of mice deficient in G6PC3 treated with empagliflozin .

Following these discoveries, the aim of the investigator's experiment is to test the effect of the efficacy of empagliflozin on urinary excretion and elimination of blood 1,5-anhydroglucitol in patients with glucose-6-phosphate transporter deficiency (type Ib glycogenosis) and patients with G6PC3 deficiency. This should allow patients to significantly lower the level of 1,5-anhydroglucitol-6-phosphate found in their neutrophils and thus cure their neutropenia.

Empagliflozin (marketed in Belgium under the name of Jardiance®) belongs to the class of drugs called oral hypoglycemic agents. It works on the kidney by inhibiting the glucose transporter in the proximal tubules, SGLT2, which leads to glucosuria that results in the elimination of 1,5-anhydroglucitol in the urine. At present, Empagliflozin alone or in combination with other drugs is commonly used in people with type 2 diabetes to control their blood sugar levels. ;

Related Conditions & MeSH terms

• Glucose 6 Phosphatase Deficiency
• Glycogen Storage Disease
• Glycogen Storage Disease Type I
• Neutropenia

• NCT number: NCT04138251
• Study type: Interventional
• Source: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Contact: Xavier Stephenne, MD, PhD
• Phone: 32 2 7641377
• Email: xavier.stephenne@uclouvain.be
• Status: Recruiting
• Phase: Phase 2
• Start date: June 20, 2019
• Completion date: June 30, 2020