Glycogen Storage Disease Type IBNCT04986735
Prospective Cohort Study of Children With GSD1b Receiving Empagliflozin
An observational study of Glycogen Storage Disease Type IB, run by Hong Kong Children's Hospital at 1 site in Hong Kong.
Trial summary
This is a prospective cohort study of children with GSD1b to evaluate their outcome after using empagliflozin for neutrophil defects. Read more about this study
- Who is it for?
- Ages 6 months to 18 years
- Conditions the study is for
- Glycogen Storage Disease Type IB
- What is being tested?
- Empagliflozin
- How many people
- 11 participants
- Where
- 1 siteHong Kong
- Study dates
- 8 Aug 2021to 31 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
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
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site, 1 recruiting
- Recruiting
Hong Kong Children's Hospital
Hong Kong
MEI KWUN KWOK, MB,BS, 852-57413216, kwokmk@ha.org.hk
About this study
Official title: Evaluation of Safety and Efficacy of Empagliflozin for Neutropenia and Neutrophil Dysfunction in Children With Glycogen Storage Disease Type 1b (GSD1b)
This is a prospective cohort study of children with GSD1b to evaluate their outcome after using empagliflozin for neutrophil defects.
Read the 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.
- Conditions
- Glycogen Storage Disease Type IB
- Being tested
- Empagliflozin
- Medical subject headings
- Glycogen Storage Disease IB
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmpagliflozinDrug
Also called Jardiance
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of empagliflozin - usage of granulocyte colony stimulating factor (GCSF)
Dosage and frequency of administration of GCSF
Measured: from the start to the 52nd week of empagliflozin treatment
Secondary outcomes (8)
Efficacy of empagliflozin - neutrophil number and function
Average neutrophil count and neutrophil oxidative burst
Measured: from the start to the 52nd week of empagliflozin treatment
Efficacy of empagliflozin - bowel manifestations
Severity of bowel inflammation, diarrhea, and aphthous ulcers
Measured: from the start to the 52nd week of empagliflozin treatment
Efficacy of empagliflozin - frequency of infections
Number of infections requiring hospitalization and antibiotics/surgical intervention
Measured: from the start to the 52nd week of empagliflozin treatment
Efficacy of empagliflozin - biochemical improvement
Blood 1,5-anhydroglucitol level and urine glucose excretion
Measured: from the start to the 52nd week of empagliflozin treatment
General metabolic control - GSD1b metabolic & imaging profile, concomitant interventions
Metabolic profile and concomitant interventions that reflects metabolic control of GSD1b
Measured: from the start to the 52nd week of empagliflozin treatment
General well being - Quality of life
Pediatric Quality of Life Inventory™ (PedsQL™) - English or Cantonese/Chinese versions
Measured: from the start to the 52nd week of empagliflozin treatment
Safety of empagliflozin - presence or absence of hypoglycemia
Frequency of symptomatic or severe hypoglycemia, average glucose levels
Measured: from the start to the 52nd week of empagliflozin treatment
Safety of empagliflozin - prescence of absence of empagliflozin-related side effects
number of empagliflozin-related adverse events
Measured: from the start to the 52nd week of empagliflozin treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2021
- Study start8 Aug 2021
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glycogen Storage Disease Type IBStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 11 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hong Kong Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kwok Mei-kwun, Hong Kong Children's Hospital
- Investigators
- Mei Kwun Kwok, Principal investigator, Hong Kong Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04986735
- Sponsor's protocol ID
- KWOK-HKCH-GSD1-EMPA
- Status last verified
- Aug 2021
- First submitted
- 27 Jul 2021
- Last updated
- 16 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Safety and Efficacy of Empagliflozin for Neutropenia and Neutrophil Dysfunction in Children With Glycogen Storage Disease Type 1b (GSD1b)
- ClinicalTrials.gov ID
- NCT04986735
- Acronym / sponsor ID
- KWOK-HKCH-GSD1-EMPA
- Conditions
- Glycogen Storage Disease Type IB
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 11 participants (estimated)
- Lead sponsor
- Hong Kong Children's HospitalUniversity, hospital or other
- Study start
- 8 Aug 2021 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 3 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 6 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- 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
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EmpagliflozinAlso: JardianceAll 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. | Drug | – |
Primary outcome
Efficacy of empagliflozin - usage of granulocyte colony stimulating factor (GCSF)
Time frame: from the start to the 52nd week of empagliflozin treatment
Dosage and frequency of administration of GCSF
8 secondary outcomes
Efficacy of empagliflozin - neutrophil number and function
Time frame: from the start to the 52nd week of empagliflozin treatment
Efficacy of empagliflozin - bowel manifestations
Time frame: from the start to the 52nd week of empagliflozin treatment
Efficacy of empagliflozin - frequency of infections
Time frame: from the start to the 52nd week of empagliflozin treatment
Efficacy of empagliflozin - biochemical improvement
Time frame: from the start to the 52nd week of empagliflozin treatment
General metabolic control - GSD1b metabolic & imaging profile, concomitant interventions
Time frame: from the start to the 52nd week of empagliflozin treatment
General well being - Quality of life
Time frame: from the start to the 52nd week of empagliflozin treatment
Safety of empagliflozin - presence or absence of hypoglycemia
Time frame: from the start to the 52nd week of empagliflozin treatment
Safety of empagliflozin - prescence of absence of empagliflozin-related side effects
Time frame: from the start to the 52nd week of empagliflozin treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mei Kwun Kwok principal investigator
Hong Kong Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Glycogen Storage Disease Type IB, run by Hong Kong Children's Hospital at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact MEI KWUN KWOK, MB,BS (852-57413216, kwokmk@ha.org.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of empagliflozin - usage of granulocyte colony stimulating factor (GCSF) (time frame: from the start to the 52nd week of empagliflozin treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2021.