Prospective Cohort Study of Children With GSD1b Receiving Empagliflozin

Sponsor
Hong Kong Children's Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT04986735
Collaborator
(none)
11
1
28.7
0.4

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase

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.

Study Design

Study Type:
Observational
Anticipated Enrollment :
11 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Evaluation of Safety and Efficacy of Empagliflozin for Neutropenia and Neutrophil Dysfunction in Children With Glycogen Storage Disease Type 1b (GSD1b)
Actual Study Start Date :
Aug 8, 2021
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Dec 31, 2023

Outcome Measures

Primary Outcome Measures

  1. Efficacy of empagliflozin - usage of granulocyte colony stimulating factor (GCSF) [from the start to the 52nd week of empagliflozin treatment]

    Dosage and frequency of administration of GCSF

Secondary Outcome Measures

  1. Efficacy of empagliflozin - neutrophil number and function [from the start to the 52nd week of empagliflozin treatment]

    Average neutrophil count and neutrophil oxidative burst

  2. Efficacy of empagliflozin - bowel manifestations [from the start to the 52nd week of empagliflozin treatment]

    Severity of bowel inflammation, diarrhea, and aphthous ulcers

  3. Efficacy of empagliflozin - frequency of infections [from the start to the 52nd week of empagliflozin treatment]

    Number of infections requiring hospitalization and antibiotics/surgical intervention

  4. Efficacy of empagliflozin - biochemical improvement [from the start to the 52nd week of empagliflozin treatment]

    Blood 1,5-anhydroglucitol level and urine glucose excretion

  5. General metabolic control - GSD1b metabolic & imaging profile, concomitant interventions [from the start to the 52nd week of empagliflozin treatment]

    Metabolic profile and concomitant interventions that reflects metabolic control of GSD1b

  6. General well being - Quality of life [from the start to the 52nd week of empagliflozin treatment]

    Pediatric Quality of Life Inventory™ (PedsQL™) - English or Cantonese/Chinese versions

  7. Safety of empagliflozin - presence or absence of hypoglycemia [from the start to the 52nd week of empagliflozin treatment]

    Frequency of symptomatic or severe hypoglycemia, average glucose levels

  8. Safety of empagliflozin - prescence of absence of empagliflozin-related side effects [from the start to the 52nd week of empagliflozin treatment]

    number of empagliflozin-related adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:
6 Months to 18 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Hong Kong Children's Hospital Hong Kong Hong Kong

Sponsors and Collaborators

  • Hong Kong Children's Hospital

Investigators

  • Principal Investigator: Mei Kwun Kwok, Hong Kong Children's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Kwok Mei-kwun, Associate Consultant, Hong Kong Children's Hospital
ClinicalTrials.gov Identifier:
NCT04986735
Other Study ID Numbers:
  • KWOK-HKCH-GSD1-EMPA
First Posted:
Aug 3, 2021
Last Update Posted:
Aug 16, 2021
Last Verified:
Aug 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 16, 2021