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

Brief Title

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

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

Brief Summary

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

Detailed 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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Empaglifozin safety (blood test-glycemia): measured by absence of hypoglycaemia due to gliflozin treatment

Secondary Outcome

 Empaglifozin Clinical efficacy (questionnaire)

Condition

Glycogen Storage Disease Type I

Intervention

Empagliflozin

Study Arms / Comparison Groups

 Treatment
Description:  Oral empaglifozin 5 mg 1x/day, increase up to 10 mg 1x/day if no 25% decrease of blood1,5-anhydroglucitol level

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

5

Start Date

June 20, 2019

Completion Date

June 30, 2020

Primary Completion Date

June 30, 2020

Eligibility Criteria

        Inclusion Criteria:

          -  Glycogenosis type 1b confirmed by biochemical analyzes and / or genetic analysis.
             These patients with Glycogenosis must have had a liver transplant

          -  Alternatively, G6PC3 deficiency confirmed by genetic analysis

          -  Age 1 to 18 years old female or male

          -  Informed consent signed by the recipient and / or parents / assigns.

          -  Information and agreement of the referring medical team.

          -  A Negative Blood Pregnancy Test at the time of screening and a negative urinary
             pregnancy test at Day 1 of the protocol are required for female with child bearing
             potential.

          -  Sexually active patients should use an effective method of contraception throughout
             the duration of the study and up to 7 days after the last dose of Empaglifozine. (The
             combination of a hormonal method and a barrier method; Two barrier methods, the male
             condom being one of these two methods;Use intrauterine device or tubal ligation;-A
             total sex abstinence.)

        Exclusion Criteria:

          -  Presence of advanced fibrosis (Metavir F4) or cirrhosis.

          -  Impossibility of long-term and / or non-compliance monitoring.

          -  Other medical problems which, in the opinion of the physicians in charge of the
             patient, would constitute a contraindication to the procedure.

          -  Sexually active patients who do not consent to use effective contraception during the
             study.
      

Gender

All

Ages

1 Year - 18 Years

Accepts Healthy Volunteers

No

Contacts

Xavier Stephenne, MD, PhD, 32 2 7641377, [email protected]

Location Countries

Belgium

Location Countries

Belgium

Administrative Informations


NCT ID

NCT04138251

Organization ID

2018/26DEC/492


Responsible Party

Sponsor

Study Sponsor

Cliniques universitaires Saint-Luc- Université Catholique de Louvain


Study Sponsor

Xavier Stephenne, MD, PhD, Principal Investigator, Cliniques universitaires St Luc


Verification Date

October 2019