Efficacy and Safety of Empagliflozin in GSD-Ib Patients

Phase 2

Recruiting

• Conditions: Glycogen Storage Disease Type IB
• Interventions: Drug: Empagliflozin

• Registration Number: NCT05960617
• Lead Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

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.

Study Timeline

• Status Verified: 2023-06
• Study First Submitted: 2023-07-05
• Study Start: 2023-07-15
• Study First Submitted QC: 2023-07-17
• Last Update Submitted: 2023-07-17
• Study First Posted: 2023-07-27
• Last Update Posted: 2023-07-27
• Primary Completion: 2024-06-30
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Oral administration of Empagliflozin	Empagliflozin	All subjects will have a baseline assessment and be prospectively followed up for 12 months to examine their outcome after receiving empagliflozin.

Primary Outcome Measures

Name	Time	Method
Occurrence of hypoglycemia	1 year	Safety and tolerability of Empaglifozin measured by hypoglycemia
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

Secondary Outcome Measures

Name	Time	Method
Change of total cholesterol	1 year	Measured as change of total cholesterol (mmol/L) compared to the period before study
Number of infections	1 year	Efficacy of Empaglifozin measured by the number of respiratory tract, skin, and urinary tract infections
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
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
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

Trial Locations

Locations (1)

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China