Glycogen Storage Disease Type IPhase 2GLYCO-1BNCT04138251
Safety, Efficacy Evaluation of Empagliflozin Administration for Neutropenia in Glycogenosis Type 1b and G6PC3 Deficiency
A Phase 2 study testing Empagliflozin in people with Glycogen Storage Disease Type I and Glucose 6 Phosphatase Deficiency, run by Cliniques universitaires Saint-Luc- Université Catholique de Louvain at 1 site in Belgium.
Trial summary
Treatment of neutropenia of G6PC3 and Glycogenosis type 1b patients with empagliflozin Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Glycogen Storage Disease Type I, Glucose 6 Phosphatase Deficiency
- What is being tested?
- Empagliflozin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteBelgium
- Study dates
- 20 Jun 2019to 30 Jun 2020
- Phase
- Phase 2
- 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 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Glycogenosis type 1b confirmed by biochemical analyzes and / or genetic analysis. These patients with Glycogenosis must have had a liver transplant
- Alternatively, G6PC3 deficiency confirmed by genetic analysis
- Age 1 to 18 years old female or male
- Informed consent signed by the recipient and / or parents / assigns.
- Information and agreement of the referring medical team.
- A Negative Blood Pregnancy Test at the time of screening and a negative urinary pregnancy test at Day 1 of the protocol are required for female with child bearing potential.
- Sexually active patients should use an effective method of contraception throughout the duration of the study and up to 7 days after the last dose of Empaglifozine. (The combination of a hormonal method and a barrier method; Two barrier methods, the male condom being one of these two methods;Use intrauterine device or tubal ligation;-A total sex abstinence.)
Who cannot join
- Presence of advanced fibrosis (Metavir F4) or cirrhosis.
- Impossibility of long-term and / or non-compliance monitoring.
- Other medical problems which, in the opinion of the physicians in charge of the patient, would constitute a contraindication to the procedure.
- Sexually active patients who do not consent to use effective contraception during the study.
Trial locations and contacts
1 site in 1 country.
Julia Versavau contact
Belgium1 site, 1 recruiting
- Recruiting
Cliniques universitaires Saint-Luc
Brussels, 1200
Xavier Stephenne, MD, PhD, 32 2 7641377, xavier.stephenne@uclouvain.be
Xavier Stephenne, MD, PhD
About this study
Official title: Evaluation of the Safety and Efficacy of Empagliflozin Administration as a Treatment for Neutropenia in Patients With Glycogenosis Type 1b and G6PC3 Deficiency
Treatment of neutropenia of G6PC3 and Glycogenosis type 1b patients with empagliflozin
Read the detailed description
Ubiquitous glucose-6-phosphatase deficiency (G6PC3) and glucose-6-phosphate transporter deficiency (G6PT/SLC37A4) both cause neutropenia. Studies on a G6PC3 deficient mouse model by Dr Veiga-da-Cunha and Prof. Van Schaftingen and colleagues have shown that these two proteins collaborate to hydrolyze a metabolite that exerts toxic effects on neutrophils. This metabolite is 1,5-anhydroglucitol-6-phosphate. It is formed by phosphorylation of a glucose analogue, 1,5-anhydroglucitol, which is present in the blood of all humans, mice and other mammals.
This discovery of the function of G6PC3 and G6PT opens up therapeutic prospects, in that lowering the concentration of 1,5-anhydroglucitol in the blood should reduce the concentration of 1,5-anhydroglucitol-6-phosphate in the cells and thus reduce its toxic effects. Veiga-da-Cunha, Van Schaftingen and colleagues have already shown that this is the case for a model of mice deficient in G6PC3 treated with empagliflozin .
Following these discoveries, the aim of the investigator's experiment is to test the effect of the efficacy of empagliflozin on urinary excretion and elimination of blood 1,5-anhydroglucitol in patients with glucose-6-phosphate transporter deficiency (type Ib glycogenosis) and patients with G6PC3 deficiency. This should allow patients to significantly lower the level of 1,5-anhydroglucitol-6-phosphate found in their neutrophils and thus cure their neutropenia.
Empagliflozin (marketed in Belgium under the name of Jardiance®) belongs to the class of drugs called oral hypoglycemic agents. It works on the kidney by inhibiting the glucose transporter in the proximal tubules, SGLT2, which leads to glucosuria that results in the elimination of 1,5-anhydroglucitol in the urine. At present, Empagliflozin alone or in combination with other drugs is commonly used in people with type 2 diabetes to control their blood sugar levels.
- Being tested
- Empagliflozin
- Keywords
- Empaglifozin
- Medical subject headings
- Glycogen Storage Disease Type I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmpagliflozinDrug
Also called Jardiance
oral administration of Empagliflozin
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Oral empaglifozin 5 mg 1x/day, increase up to 10 mg 1x/day if no 25% decrease of blood1,5-anhydroglucitol level Receives: Drug: Empagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Empaglifozin safety (blood test-glycemia): measured by absence of hypoglycaemia due to gliflozin treatment
Empaglifozin safety is measured by absence of hypoglycaemia due to gliflozin treatment (continuous monitoring during the first 2 days of treatment and glycemia punctual monitoring every 7 days for 2 months) (mg/dl)
Measured: from start of treatment to 2 months post treatment
Empaglifozin Efficacy (blood test-hemogram)
Efficacy of drug is measured by an Increased neutrophil count as compared to pre-treatment (10exp3/µl)
Measured: from start of treatment to 2 months post treatment
Secondary outcomes (5)
Empaglifozin Clinical efficacy (questionnaire)
Empaglifozin Clinical efficacy is measured as a Decrease in the number of infections
-Decrease in the number of episodes of oral aphtosis (stomatitis) We will use numerical scale: higher scores mean worse outcome
Measured: from start of treatment to 2 months post treatment
Empaglifozin Biological efficacy on blood 1,5-anhydroglucitol level (blood test-LCMS)
Empaglifozin Biological efficacy is measured as a Decrease of blood 1,5-anhydroglucitol (µM)
Measured: from start of treatment to 2 months post treatment
Empaglifozin Biological efficacy on 1,5-anhydroglucitol-6-phosphate levels in neutrophils (blood test-LCMS)
Empaglifozin Biological efficacy is measured as decrease in the level of 1,5-anhydroglucitol-6-phosphate in neutrophils (µM)
Measured: from start of treatment to 2 months post treatment
Empaglifozin Clinical efficacy on urinary 1,5-anhydroglucitol excretion increase (urine test-LCMS)
Empaglifozin Biological efficacy is measured as increased excretion of urinary 1,5-anhydroglucitol (µM)
Measured: from start of treatment to 2 months post treatment
Empaglifozin Clinical efficacy on neutrophil function (blood test)
Empaglifozin Biological efficacy is measured as improved neutrophilic function (glycosylation analysis, Western Blot)
Measured: from start of treatment to 2 months post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2019
- Study start20 Jun 2019
- Primary completion30 Jun 2020 (estimated)
- Study completion30 Jun 2020 (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 IStudies of the same condition, open and under way.
- More trials run by Cliniques universitaires Saint-Luc- Université Catholique de LouvainThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Xavier Stephenne, MD, PhD, Principal investigator, Cliniques universitaires St Luc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04138251
- Sponsor's protocol ID
- 2018/26DEC/492
- Acronym
- GLYCO-1B
- Status last verified
- Oct 2019
- First submitted
- 20 Jun 2019
- Last updated
- 28 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- 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 28 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Safety and Efficacy of Empagliflozin Administration as a Treatment for Neutropenia in Patients With Glycogenosis Type 1b and G6PC3 Deficiency
- ClinicalTrials.gov ID
- NCT04138251
- Acronym / sponsor ID
- GLYCO-1B / 2018/26DEC/492
- Keywords
- Empaglifozin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- Cliniques universitaires Saint-Luc- Université Catholique de LouvainUniversity, hospital or other
- Study start
- 20 Jun 2019 (actual)
- Primary completion
- 30 Jun 2020 (estimated)
- Study completion
- 30 Jun 2020 (estimated)
- First posted
- 24 Oct 2019 (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.
Treatment of neutropenia of G6PC3 and Glycogenosis type 1b patients with empagliflozin
Detailed description
Ubiquitous glucose-6-phosphatase deficiency (G6PC3) and glucose-6-phosphate transporter deficiency (G6PT/SLC37A4) both cause neutropenia. Studies on a G6PC3 deficient mouse model by Dr Veiga-da-Cunha and Prof. Van Schaftingen and colleagues have shown that these two proteins collaborate to hydrolyze a metabolite that exerts toxic effects on neutrophils. This metabolite is 1,5-anhydroglucitol-6-phosphate. It is formed by phosphorylation of a glucose analogue, 1,5-anhydroglucitol, which is present in the blood of all humans, mice and other mammals.
This discovery of the function of G6PC3 and G6PT opens up therapeutic prospects, in that lowering the concentration of 1,5-anhydroglucitol in the blood should reduce the concentration of 1,5-anhydroglucitol-6-phosphate in the cells and thus reduce its toxic effects. Veiga-da-Cunha, Van Schaftingen and colleagues have already shown that this is the case for a model of mice deficient in G6PC3 treated with empagliflozin .
Following these discoveries, the aim of the investigator's experiment is to test the effect of the efficacy of empagliflozin on urinary excretion and elimination of blood 1,5-anhydroglucitol in patients with glucose-6-phosphate transporter deficiency (type Ib glycogenosis) and patients with G6PC3 deficiency. This should allow patients to significantly lower the level of 1,5-anhydroglucitol-6-phosphate found in their neutrophils and thus cure their neutropenia.
Empagliflozin (marketed in Belgium under the name of Jardiance®) belongs to the class of drugs called oral hypoglycemic agents. It works on the kidney by inhibiting the glucose transporter in the proximal tubules, SGLT2, which leads to glucosuria that results in the elimination of 1,5-anhydroglucitol in the urine. At present, Empagliflozin alone or in combination with other drugs is commonly used in people with type 2 diabetes to control their blood sugar levels.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: EmpagliflozinOral empaglifozin 5 mg 1x/day, increase up to 10 mg 1x/day if no 25% decrease of blood1,5-anhydroglucitol level |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Glycogenosis type 1b confirmed by biochemical analyzes and / or genetic analysis. These patients with Glycogenosis must have had a liver transplant
- Alternatively, G6PC3 deficiency confirmed by genetic analysis
- Age 1 to 18 years old female or male
- Informed consent signed by the recipient and / or parents / assigns.
- Information and agreement of the referring medical team.
Key exclusion criteria (4 listed)
- Presence of advanced fibrosis (Metavir F4) or cirrhosis.
- Impossibility of long-term and / or non-compliance monitoring.
- Other medical problems which, in the opinion of the physicians in charge of the patient, would constitute a contraindication to the procedure.
- Sexually active patients who do not consent to use effective contraception during the study.
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: Jardianceoral administration of Empagliflozin | Drug | Treatment |
Primary outcome
Empaglifozin safety (blood test-glycemia): measured by absence of hypoglycaemia due to gliflozin treatment
Time frame: from start of treatment to 2 months post treatment
Empaglifozin safety is measured by absence of hypoglycaemia due to gliflozin treatment (continuous monitoring during the first 2 days of treatment and glycemia punctual monitoring every 7 days for 2 months) (mg/dl)
Empaglifozin Efficacy (blood test-hemogram)
Time frame: from start of treatment to 2 months post treatment
Efficacy of drug is measured by an Increased neutrophil count as compared to pre-treatment (10exp3/µl)
5 secondary outcomes
Empaglifozin Clinical efficacy (questionnaire)
Time frame: from start of treatment to 2 months post treatment
Empaglifozin Biological efficacy on blood 1,5-anhydroglucitol level (blood test-LCMS)
Time frame: from start of treatment to 2 months post treatment
Empaglifozin Biological efficacy on 1,5-anhydroglucitol-6-phosphate levels in neutrophils (blood test-LCMS)
Time frame: from start of treatment to 2 months post treatment
Empaglifozin Clinical efficacy on urinary 1,5-anhydroglucitol excretion increase (urine test-LCMS)
Time frame: from start of treatment to 2 months post treatment
Empaglifozin Clinical efficacy on neutrophil function (blood test)
Time frame: from start of treatment to 2 months post treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2019.
- Proc Natl Acad Sci U S A. 2019 Jan 22;116(4):1241-1250. doi: 10.1073/pnas.1816143116. Epub 2019 Jan 9.Link provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Glycogen Storage Disease Type I
RecruitingObservational study
Accuracy of Home Lactate Meter and Accu-chek Glucometer in Patients With Glycogen Storage Disease
Glycogen Storage Disease Type IA, Glycogen Storage Disease Type I
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Not yet recruitingObservational study
MENA/Levant Epidemiological, Registry of Immunological & Clinical Traits (MERIT)
Antiphospholipid (aPL)-Positive, Rheumatic Arthritis
Not yet recruitingObservational study
Effects of the Carbohydrate Counting Method on Blood Glucose Regulation, Quality of Life, Urinary Glc4 and Other Biomarkers in Children With GSD1
Glycogen Storage Disease Type I, Glycogen Storage Disease Type IB
RecruitingObservational study
Glycogen Storage Disease Type Ia (GSDIa) Disease Monitoring Program
Glycogen Storage Disease Type Ia
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.
Julia Versavau contact
Xavier Stephenne, MD, PhD principal investigator
Cliniques universitaires St Luc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Empagliflozin in people with Glycogen Storage Disease Type I and Glucose 6 Phosphatase Deficiency, run by Cliniques universitaires Saint-Luc- Université Catholique de Louvain at 1 site in Belgium.
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 7 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 28 Oct 2019. 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 Belgium. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Xavier Stephenne, MD, PhD (32 2 7641377, xavier.stephenne@uclouvain.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Empaglifozin safety (blood test-glycemia): measured by absence of hypoglycaemia due to gliflozin treatment (time frame: from start of treatment to 2 months post treatment). The study lists 2 primary outcomes in all. 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 28 Oct 2019.