Back to resultsEfficacy and Safety of Empagliflozin in GSD-Ib Patients
Primary Purpose
Glycogen Storage Disease Type IB
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Empagliflozin
Sponsored by
About this trial
This is an interventional treatment trial for Glycogen Storage Disease Type IB
Eligibility Criteria
Inclusion Criteria: Patients with glycogen storage disease type Ib (genetically diagnosed) aged ≥ 1 year and ≤ 50 years; 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); Subjects and their guardians/clients (< 18 years old) or subjects (≥ 18 years old) signed the informed consent form. Exclusion Criteria: Patients with chronic kidney disease (eGFR < 60 ml/min/1.73 m^2) or cirrhosis (Metavir F4); Experiencing symptomatic or severe hypoglycemia within 1 month before the start of this trial; Absolute neutrophil count continued ≥ 1.5 × 10^9/L (≥ 3 tests, each interval ≥ 5 days); Current active urinary tract infection (until urine routine twice negative); Participating other clinical investigators in the past 1 month; Pregnancy, breast-feeding and having a pregnancy plan; Presence of contraindications to empagliflozin therapy (hypersensitivity to empagliflozin, current or history of gangrene, history of recurrent urinary or genital infections); Patients who are not suitable for participating in the clinical investigator or with low compliance in the investigator 's opinion.
Sites / Locations
- Xinhua Hospital, Shanghai Jiao Tong University School of MedicineRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Oral administration of Empagliflozin
Arm Description
All subjects will have a baseline assessment and be prospectively followed up for 12 months to examine their outcome after receiving empagliflozin.
Outcomes
Primary Outcome Measures
Change from Baseline in Absolute neutrophil count at 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
Safety and tolerability of Empaglifozin measured by hypoglycemia
Secondary Outcome Measures
Number of infections
Efficacy of Empaglifozin measured by the number of respiratory tract, skin, and urinary tract infections
Inflammatory bowel disease activity
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
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
Measured as change of triglycerides (mmol/L) compared to the period before study
Change of total cholesterol
Measured as change of total cholesterol (mmol/L) compared to the period before study
Change of lactate
Measured as change of lactate (mmol/L) compared to the period before study
Change of uric acid
Measured as change of uric acid (mmol/L) compared to the period before study
Full Information
NCT ID
NCT05960617
First Posted
July 5, 2023
Last Updated
July 17, 2023
Sponsor
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT05960617
Brief Title
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
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 15, 2023 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glycogen Storage Disease Type IB
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Oral administration of Empagliflozin
Arm Type
Experimental
Arm Description
All subjects will have a baseline assessment and be prospectively followed up for 12 months to examine their outcome after receiving empagliflozin.
Intervention Type
Drug
Intervention Name(s)
Empagliflozin
Other Intervention Name(s)
Jardiance
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change from Baseline in Absolute neutrophil count at 1 year
Description
Efficacy of Empaglifozin measured by the change in absolute neutrophil count after 12 months of treatment compared to the period before study
Time Frame
1 year
Title
Occurrence of hypoglycemia
Description
Safety and tolerability of Empaglifozin measured by hypoglycemia
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Number of infections
Description
Efficacy of Empaglifozin measured by the number of respiratory tract, skin, and urinary tract infections
Time Frame
1 year
Title
Inflammatory bowel disease activity
Description
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
Time Frame
1 year
Title
Endoscopic scores of inflammatory bowel disease
Description
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
Time Frame
1 year
Title
Change of triglycerides
Description
Measured as change of triglycerides (mmol/L) compared to the period before study
Time Frame
1 year
Title
Change of total cholesterol
Description
Measured as change of total cholesterol (mmol/L) compared to the period before study
Time Frame
1 year
Title
Change of lactate
Description
Measured as change of lactate (mmol/L) compared to the period before study
Time Frame
1 year
Title
Change of uric acid
Description
Measured as change of uric acid (mmol/L) compared to the period before study
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with glycogen storage disease type Ib (genetically diagnosed) aged ≥ 1 year and ≤ 50 years;
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);
Subjects and their guardians/clients (< 18 years old) or subjects (≥ 18 years old) signed the informed consent form.
Exclusion Criteria:
Patients with chronic kidney disease (eGFR < 60 ml/min/1.73 m^2) or cirrhosis (Metavir F4);
Experiencing symptomatic or severe hypoglycemia within 1 month before the start of this trial;
Absolute neutrophil count continued ≥ 1.5 × 10^9/L (≥ 3 tests, each interval ≥ 5 days);
Current active urinary tract infection (until urine routine twice negative);
Participating other clinical investigators in the past 1 month;
Pregnancy, breast-feeding and having a pregnancy plan;
Presence of contraindications to empagliflozin therapy (hypersensitivity to empagliflozin, current or history of gangrene, history of recurrent urinary or genital infections);
Patients who are not suitable for participating in the clinical investigator or with low compliance in the investigator 's opinion.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wenjuan Qiu, MD PhD
Phone
+86-21-25076466
Email
qiuwenjuan@xinhuamed.com.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wenjuan Qiu, MD PhD
Organizational Affiliation
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200092
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenjuan Qiu, MD PhD
Phone
+86-21-25076466
Email
qiuwenjuan@xinhuamed.com.cn
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Efficacy and Safety of Empagliflozin in GSD-Ib Patients
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