Safety and Efficacy of Empagliflozin in GSD1b Patients With Neutropenia

Study Overview
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Brief Summary
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Treatment of neutropenia of Glycogenosis type 1b patients with empagliflozin

Detailed Description
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Symptoms of glycogen storage disease type Ib (GSD Ib) include - among others - hypoglycemia, hepatomegaly and neutropenia with concomitant neutrophil dysfunction, which results in recurrent bacterial and fungal infections, and inflammatory bowel disease. At present filgrastim is the only available drug to treat neutropenia in GSD Ib patients; it stimulates neutrophil production, but doesn't restore their function. Part of GSD Ib patients doesn't respond to filgrastim treatment. The latest research results showed, that neutropenia and neutrophil dysfunction in GSD Ib patients are results of extensive accumulation of 1,5-anhydroglucitol-phosphate. Empagliflozin, a SGLT2 inhibitor, inhibits renal glucose and 1,5-anhydroglucitol reabsorption and is an effective and safe method of treatment of neutropenia in this group of patients. Empagliflozin (Jardiance®) is a drug, which is registered in Poland to treat type II diabetes in adults. The aim of our study is to evaluate the efficacy and safety of neutropenia in patients with GSD Ib with empagliflozin (Jardiance®).

Official Title
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Evaluation of Efficacy and Safety of Empagliflozin in Treatment of Neutropenia in Patients With Glycogenosis Ib

Conditions
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Glucose 6 Phosphatase Deficiency

Intervention / Treatment
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* Drug: Empagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Minimum age 4 weeks old female Or Male GSD1b confirmed by genetic analysis with neutropenia and/or reduced respiratory burst Informed consent signed by the parents/assigns, and the recipient (>13 years old) Exclusion Criteria: Risk of non-compliance Chronic renal diseases (eGFR < 60 ml/min/1,73 m2) Active urinary tract infection (temporal criterion, up to recovery) Participation in another clinical trial (minimum 6 months from the end of participation until the date of signing the Informed Consent Form) Participation in therapeutic experiment, in addition to the experimental treatment with empagliflozin (minimum 12 months from the end of participation until the date of signing the Informed Consent Form) Pregnancy, breastfeeding Allergy to Empagliflozin Lack of informed consent

Ages Eligible for Study
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Minimum Age: 4 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oral administration of Empagliflozin<br> | Drug: Empagliflozin<br>* dosis depending on body weight: <20 kg 5 mg 1x/day; 20-40 kg 2 x 5 mg; >40 kg 2 x 10 mg<br>* Other names: Jardiance;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Empaglifozin safety and tolerability measured by occurrence of adverse reactions | Empaglifozin saftey and tolerability measured by occurrence of adverse reactions | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of neutropenia treatment measured as percentage of the patients | who achieved >500 neutrophils/ml for at least 6 months with normalization of oxidative burst with decrease of bacterial and fungal infections compared to the period before study with decrease of hospitalization number with decrease of the number of defecation, gingival sores, and calprotectin average concentration in stool | 2 years | 
| Dosis change/withdrawal of filgrastrim | Dosis change/withdrawal of filgrastrim | 2 years | 
| Degree of metabolic compensation | measured as change of triglycerides (mg/dL), lactate (mg/dL), and uric acid (mg/dL) compared to the period before study | 2 years |