Glycogen Storage Disease Type IB
Conditions
Brief summary
Empagliflozin Treatment of GSD-1b patients
Detailed description
Glycogen storage disease type Ib (GSD-Ib) is a type of genetic disease with a prevalence of approximately 1 in 500,000. In addition to phenotypes common to GSD-I such as hypoglycemia, hypoglycemia, lactatemia, hyperlipidemia, hyperuricemia, and hepatomegaly, GSD-Ib patients also experience neutropenia and dysfunction, causing infections and inflammatory bowel disease (IBD). At present, the only available treatment for neutropenia in GSD-Ib patients is subcutaneous injection of granulocyte-colony stimulating factor (G-CSF). G-CSF increases the number of neutrophils, but does not improve neutrophil dysfunction, and is also associated with the risk of concurrent splenomegaly and malignancy. The most recent research findings demonstrated that substantial accumulation of 1,5-anhydroglucitol-phosphate is the cause of neutropenia and neutrophil dysfunction in GSD Ib patients. Empagliflozin, an SGLT2 inhibitor, is an efficient and secure approach of treating neutropenia in these patients by inhibiting renal glucose and 1,5-anhydroglucitol reabsorption. Our study's objective is to assess the efficacy and safety of empagliflozin (Jardiance®) in patients with GSD Ib.
Interventions
DRUGEmpagliflozin
Oral administration of Empagliflozin: The starting dose was 0.3 mg/kg/day in 2 divided doses for 3 months. If the subject had an absolute neutrophil count \> 1.0 × 10\^9/L and clinical improvement (decreased number of infections and/or decreased IBD activity within 3 months), the maintenance dose was maintained. If the subject had an absolute neutrophil count \< 1.0 × 10\^9/L but clinical improvement (decreased number of infections and/or decreased IBD activity within 3 months), the maintenance dose was maintained and reassessed 1 month later. If the subject had an absolute neutrophil count \< 1.0 × 10\^9/L and no clinical improvement (no change in number of infections and/or no change in IBD activity within 3 months), the dose was increased by 0.1 mg/kg/day and reassessed 3 months later. Assessments were then performed every 3 months with the same dose modification criteria as above.
Sponsors
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with glycogen storage disease type Ib (genetically diagnosed) aged ≥ 1 year and ≤ 50 years; 2. Patients meet the diagnostic criteria for Crohn's disease (CD) based on Expert consensus on the diagnosis and treatment of inflammatory bowel disease in Chinese children (2019) or Consensus opinion on the diagnosis and treatment of inflammatory bowel disease in China (2018), or patients meet the diagnostic criteria for recurrent respiratory tract infection based on Clinical diagnosis and treatment for recurrent respiratory tract infection in Chinese children (2022); 3. Subjects and their guardians/clients (\< 18 years old) or subjects (≥ 18 years old) signed the informed consent form.
Exclusion criteria
1. Patients with chronic kidney disease (eGFR \< 60 ml/min/1.73 m\^2) or cirrhosis (Metavir F4); 2. Experiencing symptomatic or severe hypoglycemia within 1 month before the start of this trial; 3. Absolute neutrophil count continued ≥ 1.5 × 10\^9/L (≥ 3 tests, each interval ≥ 5 days); 4. Current active urinary tract infection (until urine routine twice negative); 5. Participating other clinical investigators in the past 1 month; 6. Pregnancy, breast-feeding and having a pregnancy plan; 7. Presence of contraindications to empagliflozin therapy (hypersensitivity to empagliflozin, current or history of gangrene, history of recurrent urinary or genital infections); 8. Patients who are not suitable for participating in the clinical investigator or with low compliance in the investigator 's opinion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Absolute neutrophil count at 1 year | 1 year | Efficacy of Empaglifozin measured by the change in absolute neutrophil count after 12 months of treatment compared to the period before study |
| Occurrence of hypoglycemia | 1 year | Safety and tolerability of Empaglifozin measured by hypoglycemia |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of infections | 1 year | Efficacy of Empaglifozin measured by the number of respiratory tract, skin, and urinary tract infections |
| Inflammatory bowel disease activity | 1 year | Measured as classical Crohn 's disease activity index (CDAI) for adults (range from 0 to 600; remission \<150; mildly active disease 150-219; moderately active disease 220- 450; severely active disease ≥ 450) or pediatric Crohn' s disease activity index (PCDAI) for children (range from 0 to 100; remission \<10; mildly active disease 10-27.5; moderately active disease 30-37.5; severely active disease 40-100) after 3, 6, 9, and 12 months of treatment compared to the period before study |
| Endoscopic scores of inflammatory bowel disease | 1 year | Measured as difference in Crohn 's Disease Simplified Endoscopic Score (SES-CD) (range from 0 to 17; remission 0-2; mild endoscopic activity 3-6; moderate endoscopic activity 7-15; severe endoscopic activity \>15) before and after 1 year of empagliflozin treatment |
| Change of triglycerides | 1 year | Measured as change of triglycerides (mmol/L) compared to the period before study |
| Change of total cholesterol | 1 year | Measured as change of total cholesterol (mmol/L) compared to the period before study |
| Change of lactate | 1 year | Measured as change of lactate (mmol/L) compared to the period before study |
| Change of uric acid | 1 year | Measured as change of uric acid (mmol/L) compared to the period before study |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORWenjuan Qiu, MD PhD
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Outcome results
None listed