Clinical trial NCT04986735: Prospective Cohort Study of Children With GSD1b Receiving Empagliflozin
Official title: Evaluation of Safety and Efficacy of Empagliflozin for Neutropenia and Neutrophil Dysfunction in Children With Glycogen Storage Disease Type 1b (GSD1b)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Glycogen Storage Disease Type IB
Lead sponsor: Hong Kong Children's Hospital
Sponsor class: OTHER
First posted: 2021-08-03
Enrollment: 11
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: GSD 1b patients (aged 6 months to 18 years) with diagnosis confirmed by enzymatic and/or genetic analysis, and has been on regular GCSF treatment for \>= 1 month

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy of empagliflozin - usage of granulocyte colony stimulating factor (GCSF)
timeFrame: from the start to the 52nd week of empagliflozin treatment
Secondary outcomes:
measure: Efficacy of empagliflozin - neutrophil number and function
timeFrame: from the start to the 52nd week of empagliflozin treatment
measure: Efficacy of empagliflozin - bowel manifestations
timeFrame: from the start to the 52nd week of empagliflozin treatment
measure: Efficacy of empagliflozin - frequency of infections
timeFrame: from the start to the 52nd week of empagliflozin treatment
measure: Efficacy of empagliflozin - biochemical improvement
timeFrame: from the start to the 52nd week of empagliflozin treatment
measure: General metabolic control - GSD1b metabolic & imaging profile, concomitant interventions
timeFrame: from the start to the 52nd week of empagliflozin treatment
measure: General well being - Quality of life
timeFrame: from the start to the 52nd week of empagliflozin treatment
measure: Safety of empagliflozin - presence or absence of hypoglycemia
timeFrame: from the start to the 52nd week of empagliflozin treatment
measure: Safety of empagliflozin - prescence of absence of empagliflozin-related side effects
timeFrame: from the start to the 52nd week of empagliflozin treatment
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Hong Kong Children's Hospital
Study officials:
affiliation: Hong Kong Children's Hospital
name: Mei Kwun Kwok
role: PRINCIPAL_INVESTIGATOR
References: