Efficacy and Safety of Empagliflozin in GSD-Ib Patients

NCT ID: NCT05960617

Last Updated: 2023-07-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-15
• Study Completion Date: 2024-12-31

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.

Conditions

Glycogen Storage Disease Type IB

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oral administration of Empagliflozin

All subjects will have a baseline assessment and be prospectively followed up for 12 months to examine their outcome after receiving empagliflozin.

Group Type: EXPERIMENTAL

Empagliflozin

Intervention Type: DRUG

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.

Interventions

Empagliflozin

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.

Intervention Type: DRUG

Other Intervention Names

Jardiance

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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wenjuan Qiu, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Locations

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wenjuan Qiu, MD PhD

Role: CONTACT

qiuwenjuan@xinhuamed.com.cn

+86-21-25076466

Facility Contacts

Wenjuan Qiu, MD PhD

Role: primary

qiuwenjuan@xinhuamed.com.cn

+86-21-25076466

Other Identifiers

XHEC-C-2023-051-2

Identifier Type: -

Identifier Source: org_study_id