Clinical trial NCT05960617: Efficacy and Safety of Empagliflozin in GSD-Ib Patients
Official title: Efficacy and Safety of Empagliflozin in Patients With Glycogen Storage Disease Type Ib
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Glycogen Storage Disease Type IB
Lead sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2023-07-27
Enrollment: 10
Sex: ALL
Minimum age (years): 1
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from Baseline in Absolute neutrophil count at 1 year
timeFrame: 1 year
measure: Occurrence of hypoglycemia
timeFrame: 1 year
Secondary outcomes:
measure: Number of infections
timeFrame: 1 year
measure: Inflammatory bowel disease activity
timeFrame: 1 year
measure: Endoscopic scores of inflammatory bowel disease
timeFrame: 1 year
measure: Change of triglycerides
timeFrame: 1 year
measure: Change of total cholesterol
timeFrame: 1 year
measure: Change of lactate
timeFrame: 1 year
measure: Change of uric acid
timeFrame: 1 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Wenjuan Qiu, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: