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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04138251
Recruitment Status : Unknown
Verified October 2019 by Cliniques universitaires Saint-Luc- Université Catholique de Louvain.
Recruitment status was:  Recruiting
First Posted : October 24, 2019
Last Update Posted : October 28, 2019
Sponsor:
Information provided by (Responsible Party):
Cliniques universitaires Saint-Luc- Université Catholique de Louvain

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

Condition or disease Intervention/treatment Phase
Glycogen Storage Disease Type I Glucose 6 Phosphatase Deficiency Drug: Empagliflozin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 20, 2019
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2020


Arm Intervention/treatment
Experimental: Treatment
Oral empaglifozin 5 mg 1x/day, increase up to 10 mg 1x/day if no 25% decrease of blood1,5-anhydroglucitol level
Drug: Empagliflozin
oral administration of Empagliflozin
Other Name: Jardiance




Primary Outcome Measures :
  1. Empaglifozin safety (blood test-glycemia): measured by absence of hypoglycaemia due to gliflozin treatment [ Time Frame: from start of treatment to 2 months post treatment ]
    Empaglifozin safety is measured by absence of hypoglycaemia due to gliflozin treatment (continuous monitoring during the first 2 days of treatment and glycemia punctual monitoring every 7 days for 2 months) (mg/dl)

  2. Empaglifozin Efficacy (blood test-hemogram) [ Time Frame: from start of treatment to 2 months post treatment ]
    Efficacy of drug is measured by an Increased neutrophil count as compared to pre-treatment (10exp3/µl)


Secondary Outcome Measures :
  1. Empaglifozin Clinical efficacy (questionnaire) [ Time Frame: from start of treatment to 2 months post treatment ]

    Empaglifozin Clinical efficacy is measured as a Decrease in the number of infections

    -Decrease in the number of episodes of oral aphtosis (stomatitis) We will use numerical scale: higher scores mean worse outcome


  2. Empaglifozin Biological efficacy on blood 1,5-anhydroglucitol level (blood test-LCMS) [ Time Frame: from start of treatment to 2 months post treatment ]
    Empaglifozin Biological efficacy is measured as a Decrease of blood 1,5-anhydroglucitol (µM)

  3. Empaglifozin Biological efficacy on 1,5-anhydroglucitol-6-phosphate levels in neutrophils (blood test-LCMS) [ Time Frame: from start of treatment to 2 months post treatment ]
    Empaglifozin Biological efficacy is measured as decrease in the level of 1,5-anhydroglucitol-6-phosphate in neutrophils (µM)

  4. Empaglifozin Clinical efficacy on urinary 1,5-anhydroglucitol excretion increase (urine test-LCMS) [ Time Frame: from start of treatment to 2 months post treatment ]
    Empaglifozin Biological efficacy is measured as increased excretion of urinary 1,5-anhydroglucitol (µM)

  5. Empaglifozin Clinical efficacy on neutrophil function (blood test) [ Time Frame: from start of treatment to 2 months post treatment ]
    Empaglifozin Biological efficacy is measured as improved neutrophilic function (glycosylation analysis, Western Blot)



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Ages Eligible for Study:   1 Year to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04138251


Contacts
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Contact: Xavier Stephenne, MD, PhD 32 2 7641377 xavier.stephenne@uclouvain.be
Contact: Julia Versavau 32 2 7641933

Locations
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Belgium
Cliniques universitaires Saint-Luc Recruiting
Brussels, Belgium, 1200
Contact: Xavier Stephenne, MD, PhD    32 2 7641377    xavier.stephenne@uclouvain.be   
Principal Investigator: Xavier Stephenne, MD, PhD         
Sponsors and Collaborators
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Investigators
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Principal Investigator: Xavier Stephenne, MD, PhD Cliniques universitaires St Luc
Additional Information:
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Responsible Party: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
ClinicalTrials.gov Identifier: NCT04138251    
Other Study ID Numbers: 2018/26DEC/492
First Posted: October 24, 2019    Key Record Dates
Last Update Posted: October 28, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:
Empaglifozin
Additional relevant MeSH terms:
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Neutropenia
Glycogen Storage Disease
Glycogen Storage Disease Type I
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Empagliflozin
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs