Prospective Cohort Study of Children With GSD1b Receiving Empagliflozin

Glycogen Storage Disease Type IB Clinical Trial

Official title:

Evaluation of Safety and Efficacy of Empagliflozin for Neutropenia and Neutrophil Dysfunction in Children With Glycogen Storage Disease Type 1b (GSD1b)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04986735
• Other study ID #: KWOK-HKCH-GSD1-EMPA
• Status: Recruiting
• Start date: August 8, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: August 2021
• Source: Hong Kong Children's Hospital
• Contact: MEI KWUN KWOK, MB,BS
• Phone: 852-57413216
• Email: kwokmk[@]ha.org.hk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a prospective cohort study of children with GSD1b to evaluate their outcome after using empagliflozin for neutrophil defects.

Description:

Glycogen Storage Disease Type 1b (GSD1b) is an ultra-rare inborn error of carbohydrate metabolism, characterized by low neutrophil count, neutrophil dysfunction, and the associated recurrent infections and inflammatory bowel conditions.

The current standard treatment with granulocyte colony-stimulating factor (GCSF) only increases neutrophil count but does not improve neutrophil function. It achieves only partial clinical response. Fever, recurrent infections, and gastrointestinal upset remain significant problems. Long-term regular GCSF injection is needed to sustain the clinical effect, but is also associated with development of serious complications including massive spleen enlargement, acute myeloid leukemia and myelodysplastic syndrome.

Accumulation of a toxic metabolite called 1,5-anhydroglucitol-6-phosphate (1,5AG6P) is recently discovered as the cause of neutrophil problems in GSD1b. Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor widely used as anti-diabetic drug, is known to promote excretion of 1,5-anhydroglucitol (1,5AG) in kidney. Since 1,5AG is the precursor of 1,5AG6P, empagliflozin also reduces the accumulation of 1,5AG6P. This is confirmed by animal studies that empagliflozin is shown to improve neutrophil count and function in GSD1b mouse model. Similar benefits are also recently reported in human cases (3 adults and 2 children with GSD1b), that GCSF dose could be significantly reduced or even stopped.

This is a prospective cohort study of children with GSD1b to examine their outcome after receiving empagliflozin treatment. The objective is to evaluate the short to medium term safety and efficacy of empagliflozin. The ultimate goal is to assess if SGLT2 inhibitor could be an effective alternative of GCSF with less side effects and risks, and to improve the clinical outcomes and quality of life for patients and families with GSD1b.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 11
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 18 Years

Eligibility

Inclusion Criteria:

• Subject (aged 6 months to 18 years) is enzymatically/genetically confirmed to have GSD 1b and has been on regular GCSF treatment for >= 1 month

Exclusion Criteria:

• Subject fails to provide relevant background medical information, or comply with all requirements of the clinical trial, or sign the informed consent

• Subject has any co-morbidity or condition that could increase the risk of empagliflozin treatment (e.g. renal failure with eGFR <30 mL/min/1.73m2 or requiring dialysis, diabetes requiring insulin &/or oral hypoglycemic agents, dyslipidemia requiring pharmacological intervention)

• Subject is pregnant, or a sexually active female who does not consent to use effective contraception during the study

• History of liver transplantation is NOT an exclusion criterium

Related Conditions & MeSH terms

• Glycogen Storage Disease
• Glycogen Storage Disease Type IB

Intervention

Drug:
• Empagliflozin
All subjects will have a baseline assessment and be prospectively followed up for 52 weeks to examine their outcome after receiving empagliflozin for neutropenia and neutrophil dysfunction.

Locations

Country	Name	City	State
Hong Kong	Hong Kong Children's Hospital	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
Hong Kong Children's Hospital

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of empagliflozin - usage of granulocyte colony stimulating factor (GCSF)	Dosage and frequency of administration of GCSF	from the start to the 52nd week of empagliflozin treatment
Secondary	Efficacy of empagliflozin - neutrophil number and function	Average neutrophil count and neutrophil oxidative burst	from the start to the 52nd week of empagliflozin treatment
Secondary	Efficacy of empagliflozin - bowel manifestations	Severity of bowel inflammation, diarrhea, and aphthous ulcers	from the start to the 52nd week of empagliflozin treatment
Secondary	Efficacy of empagliflozin - frequency of infections	Number of infections requiring hospitalization and antibiotics/surgical intervention	from the start to the 52nd week of empagliflozin treatment
Secondary	Efficacy of empagliflozin - biochemical improvement	Blood 1,5-anhydroglucitol level and urine glucose excretion	from the start to the 52nd week of empagliflozin treatment
Secondary	General metabolic control - GSD1b metabolic & imaging profile, concomitant interventions	Metabolic profile and concomitant interventions that reflects metabolic control of GSD1b	from the start to the 52nd week of empagliflozin treatment
Secondary	General well being - Quality of life	Pediatric Quality of Life Inventory™ (PedsQL™) - English or Cantonese/Chinese versions	from the start to the 52nd week of empagliflozin treatment
Secondary	Safety of empagliflozin - presence or absence of hypoglycemia	Frequency of symptomatic or severe hypoglycemia, average glucose levels	from the start to the 52nd week of empagliflozin treatment
Secondary	Safety of empagliflozin - prescence of absence of empagliflozin-related side effects	number of empagliflozin-related adverse events	from the start to the 52nd week of empagliflozin treatment