Crohn's DiseasePhase 1NCT05078879
Empagliflozin as a Treatment for Severe Congenital Neutropenia Due to G6PC3 Deficiency
A Phase 1 study testing Empagliflozin in people with Crohn's Disease and Glycogen Metabolism, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: Severe congenital neutropenia (SCN) is an immune system disease. People with SCN do not have enough of a kind of white blood cell called neutrophils. This means they get sick easily from infections. Some drugs to treat SCN have lots of side effects. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Crohn's Disease, Glycogen Metabolism, Inflammatory Bowel Disease (IBD)
- What is being tested?
- Empagliflozin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Nov 2021to 21 May 2025
- Phase
- Phase 1
- 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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged >=18 years.
- Documented SCN due to G6PC3 deficiency defined by genetic testing.
- History of ANC consistently <1000 cells/microL when not treated with G-CSF.
- Current ANC<1000 cells/microL when not treated with G-CSF.
- Participants must agree not to become pregnant for the duration of the study. Study participants must use 2 methods of birth control when engaging in sexual activities that can result in pregnancy, beginning 30 days before the first dose of empagliflozin through one month after treatment ends. One method must be a male or female condom. The other method may be any of the following:
- Hormonal contraception.
Show all 9Show fewer
- Diaphragm or cervical cap with a spermicide.
- Intrauterine device.
- Able to provide informed consent.
Who cannot join
- Individuals meeting any of the following criteria will be excluded from study participation:
- Renal failure or eGFR<45 mL/min/1.73 m^2.
- Type 1 diabetes mellitus.
- Fasting hypoglycemia (<60 mg/dL).
- Known hypersensitivity or allergy to any component of empagliflozin.
- Pregnant.
- Breastfeeding.
- Any condition that, in the opinion of the investigator, contraindicates participation in this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Phase 1 Study of Empagliflozin as Treatment for Severe Congenital Neutropenia Due to G6PC3 Deficiency
Background:
Severe congenital neutropenia (SCN) is an immune system disease. People with SCN do not have enough of a kind of white blood cell called neutrophils. This means they get sick easily from infections. Some drugs to treat SCN have lots of side effects. Researchers want to see if a the drug empagliflozin can help increase the number of neutrophils in a person with SCN.
Read more
Objective:
To see if a drug called empagliflozin can help people with SCN.
Eligibility:
Adults aged 18 and older with SCN.
Design:
Participants will be screened with a physical exam, medical history, and blood tests. They may have a pregnancy test.
Participants will have study visits and local lab visits. They will repeat the screening tests. They will have heart and lung function tests. They will have an ultrasound of the liver and spleen. Their skin symptoms will be photographed. They may have consultations with specialists. They may give a stool sample. They may have an optional colonoscopy with tissue sample collection. They may have an optional bone marrow biopsy and aspirate. They may have an optional magnetic resonance imaging scan of their heart.
Participants will be admitted to NIH for 5 7 days. They will start taking the study drug as a pill once daily. They will be monitored for side effects.
Participants will take the study drug at home for 12 months. They will use a fingerstick blood glucose meter to measure blood sugar at home.
Participants may be able to take the study drug through their local doctor after the study ends.
Participation will last for 15 months.
Read the detailed description
One symptom of G6PC3 deficiency is recurrent infections resulting from severe congenital neutropenia (SCN). Data suggest that SCN is the result of accumulation of the toxic dietary metabolite 1,5 anhydroglucitol 6 phosphate (1,5-AG6P) in leukocytes. This buildup inhibits glycolytic metabolism, thus impairing their function. Increasing urinary glucose excretion results in the urinary excretion of the precursor to 1,5-AG6P, and will likely reduce levels of 1,5-AG6P in leukocytes.
In this phase 1 open-label study, we will evaluate the safety, tolerability, and efficacy of the sodium glucose co transporter 2 inhibitor empagliflozin in patients with G6PC3 deficiency. Empagliflozin is FDA approved in doses of 10 or 25 mg daily for treatment of type 2 diabetes in adults. Eligible participants (n=5) aged >=18 years will be on a 2-month daily regimen of 10 mg of oral empagliflozin (phase A). Participants may then be increased to 25 mg daily (phase B) if the participant fails to achieve an adequate improvement in neutropenia during phase A and is able to tolerate the higher dose, or alternatively may continue on the 10-mg dose. Participants will temporarily discontinue any current granulocyte colony-stimulating factor (G-CSF) regimen starting at least 7 days before the empagliflozin regimen begins, to remove or reduce the effects of concomitant G-CSF so the baseline ANC can be evaluated without confounding factors.
During phase A, participants will have blood drawn locally every two weeks for clinical lab evaluations (including ANC). A member of the study team will also contact the participant for remote AE assessment at each blood draw. During phase B, blood draws and remote AE assessments will be monthly for the first 4 months, and bimonthly for the last 6 months. Participants will have outpatient study visits at the NIH Clinical Center at the end of phase A (month 2), and at months 6 and 12 during phase B.
- Being tested
- Empagliflozin
- Keywords
- Glycogen metabolism, Jardiance, Inflammatory Bowe Disease (IBD), G6PT deficiency, 1,5-AG
- Medical subject headings
- Crohn Disease, Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmpagliflozinDrug
This is an open-label pilot study to evaluate the efficacy, safety, and tolerability of empagliflozin as a treatment for severe congenital neutropenia (SCN) in patients with glucose-6-phosphatase 3 (G6PC3) deficiency. Participants will be on a 12-month daily regimen of empagliflozin at a starting dose of 10 mg (phase A), which may be increased after 2 months to 25 mg (phase B). Evaluate the safety and efficacy of the biomarker response (the change in absolute neutrophil count [ANC] after one year of empagliflozin treatment relative to baseline ANC prior to drug treatment) in patients with G6PC3 deficiency.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Patients with GCPC3 will receive daily Empagliflozin for 12 months. Receives: Drug: Empagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute Neutrophil Count
ANC increase by >500 cells/uL over baseline (measured at least 3x over 2 days)
Measured: End of Treatment at 12 months
Safety
No Grade 3/4 toxicities that require pause of the study drug.
Measured: End of Treatment at 12 months
Secondary outcomes (1)
Neutrophil Function
Improved in vitro NADPH oxidase function, Staphylococcus aureus killing assay, and chemotaxis assay.
Measured: End of Treatment at 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2021
- Study start16 Nov 2021
- Primary completion2 May 2025
- Study completion21 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- David H McDermott, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05078879
- Sponsor's protocol ID
- 10000236
- Other IDs
- 000236-I
- Status last verified
- Jun 2025
- First submitted
- 14 Oct 2021
- Last updated
- 26 Jun 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Banka S, Newman WG. A clinical and molecular review of ubiquitous glucose-6-phosphatase deficiency caused by G6PC3 mutations. Orphanet J Rare Dis. 2013 Jun 13;8:84. doi: 10.1186/1750-1172-8-84.
PubMed 23758768Dale DC, Bolyard AA, Marrero T, Kelley ML, Makaryan V, Tran E, Leung J, Boxer LA, Kishnani PS, Austin S, Wanner C, Ferrecchia IA, Khalaf D, Maze D, Kurtzberg J, Zeidler C, Welte K, Weinstein DA. Neutropenia in glycogen storage disease Ib: outcomes for patients treated with granulocyte colony-stimulating factor. Curr Opin Hematol. 2019 Jan;26(1):16-21. doi: 10.1097/MOH.0000000000000474.
PubMed 30451720Boztug K, Appaswamy G, Ashikov A, Schaffer AA, Salzer U, Diestelhorst J, Germeshausen M, Brandes G, Lee-Gossler J, Noyan F, Gatzke AK, Minkov M, Greil J, Kratz C, Petropoulou T, Pellier I, Bellanne-Chantelot C, Rezaei N, Monkemoller K, Irani-Hakimeh N, Bakker H, Gerardy-Schahn R, Zeidler C, Grimbacher B, Welte K, Klein C. A syndrome with congenital neutropenia and mutations in G6PC3. N Engl J Med. 2009 Jan 1;360(1):32-43. doi: 10.1056/NEJMoa0805051.
PubMed 19118303
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Empagliflozin as Treatment for Severe Congenital Neutropenia Due to G6PC3 Deficiency
- ClinicalTrials.gov ID
- NCT05078879
- Acronym / sponsor ID
- 10000236
- Keywords
- Glycogen metabolism, Jardiance, Inflammatory Bowe Disease (IBD), G6PT deficiency, 1,5-AG
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 16 Nov 2021 (actual)
- Primary completion
- 2 May 2025 (actual)
- Study completion
- 21 May 2025 (actual)
- First posted
- 15 Oct 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.
Background:
Severe congenital neutropenia (SCN) is an immune system disease. People with SCN do not have enough of a kind of white blood cell called neutrophils. This means they get sick easily from infections. Some drugs to treat SCN have lots of side effects. Researchers want to see if a the drug empagliflozin can help increase the number of neutrophils in a person with SCN.
Objective:
To see if a drug called empagliflozin can help people with SCN.
Eligibility:
Adults aged 18 and older with SCN.
Design:
Participants will be screened with a physical exam, medical history, and blood tests. They may have a pregnancy test.
Participants will have study visits and local lab visits. They will repeat the screening tests. They will have heart and lung function tests. They will have an ultrasound of the liver and spleen. Their skin symptoms will be photographed. They may have consultations with specialists. They may give a stool sample. They may have an optional colonoscopy with tissue sample collection. They may have an optional bone marrow biopsy and aspirate. They may have an optional magnetic resonance imaging scan of their heart.
Participants will be admitted to NIH for 5 7 days. They will start taking the study drug as a pill once daily. They will be monitored for side effects.
Participants will take the study drug at home for 12 months. They will use a fingerstick blood glucose meter to measure blood sugar at home.
Participants may be able to take the study drug through their local doctor after the study ends.
Participation will last for 15 months.
Detailed description
One symptom of G6PC3 deficiency is recurrent infections resulting from severe congenital neutropenia (SCN). Data suggest that SCN is the result of accumulation of the toxic dietary metabolite 1,5 anhydroglucitol 6 phosphate (1,5-AG6P) in leukocytes. This buildup inhibits glycolytic metabolism, thus impairing their function. Increasing urinary glucose excretion results in the urinary excretion of the precursor to 1,5-AG6P, and will likely reduce levels of 1,5-AG6P in leukocytes.
In this phase 1 open-label study, we will evaluate the safety, tolerability, and efficacy of the sodium glucose co transporter 2 inhibitor empagliflozin in patients with G6PC3 deficiency. Empagliflozin is FDA approved in doses of 10 or 25 mg daily for treatment of type 2 diabetes in adults. Eligible participants (n=5) aged >=18 years will be on a 2-month daily regimen of 10 mg of oral empagliflozin (phase A). Participants may then be increased to 25 mg daily (phase B) if the participant fails to achieve an adequate improvement in neutropenia during phase A and is able to tolerate the higher dose, or alternatively may continue on the 10-mg dose. Participants will temporarily discontinue any current granulocyte colony-stimulating factor (G-CSF) regimen starting at least 7 days before the empagliflozin regimen begins, to remove or reduce the effects of concomitant G-CSF so the baseline ANC can be evaluated without confounding factors.
During phase A, participants will have blood drawn locally every two weeks for clinical lab evaluations (including ANC). A member of the study team will also contact the participant for remote AE assessment at each blood draw. During phase B, blood draws and remote AE assessments will be monthly for the first 4 months, and bimonthly for the last 6 months. Participants will have outpatient study visits at the NIH Clinical Center at the end of phase A (month 2), and at months 6 and 12 during phase B.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: EmpagliflozinPatients with GCPC3 will receive daily Empagliflozin for 12 months. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
Key exclusion criteria (8 listed)
- Individuals meeting any of the following criteria will be excluded from study participation:
- Renal failure or eGFR<45 mL/min/1.73 m^2.
- Type 1 diabetes mellitus.
- Fasting hypoglycemia (<60 mg/dL).
- Known hypersensitivity or allergy to any component of empagliflozin.
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 |
|---|---|---|
| EmpagliflozinThis is an open-label pilot study to evaluate the efficacy, safety, and tolerability of empagliflozin as a treatment for severe congenital neutropenia (SCN) in patients with glucose-6-phosphatase 3 (G6PC3) deficiency. Participants will be on a 12-month daily regimen of empagliflozin at a starting dose of 10 mg (phase A), which may be increased after 2 months to 25 mg (phase B). Evaluate the safety and efficacy of the biomarker response (the change in absolute neutrophil count [ANC] after one year of empagliflozin treatment relative to baseline ANC prior to drug treatment) in patients with G6PC3 deficiency. | Drug | Treatment Arm |
Primary outcome
Absolute Neutrophil Count
Time frame: End of Treatment at 12 months
ANC increase by >500 cells/uL over baseline (measured at least 3x over 2 days)
Safety
Time frame: End of Treatment at 12 months
No Grade 3/4 toxicities that require pause of the study drug.
1 secondary outcome
Neutrophil Function
Time frame: End of Treatment at 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2025.
- Background: PubMed 23758768Banka S, Newman WG. A clinical and molecular review of ubiquitous glucose-6-phosphatase deficiency caused by G6PC3 mutations. Orphanet J Rare Dis. 2013 Jun 13;8:84. doi: 10.1186/1750-1172-8-84.
- Background: PubMed 30451720Dale DC, Bolyard AA, Marrero T, Kelley ML, Makaryan V, Tran E, Leung J, Boxer LA, Kishnani PS, Austin S, Wanner C, Ferrecchia IA, Khalaf D, Maze D, Kurtzberg J, Zeidler C, Welte K, Weinstein DA. Neutropenia in glycogen storage disease Ib: outcomes for patients treated with granulocyte colony-stimulating factor. Curr Opin Hematol. 2019 Jan;26(1):16-21. doi: 10.1097/MOH.0000000000000474.
- Background: PubMed 19118303Boztug K, Appaswamy G, Ashikov A, Schaffer AA, Salzer U, Diestelhorst J, Germeshausen M, Brandes G, Lee-Gossler J, Noyan F, Gatzke AK, Minkov M, Greil J, Kratz C, Petropoulou T, Pellier I, Bellanne-Chantelot C, Rezaei N, Monkemoller K, Irani-Hakimeh N, Bakker H, Gerardy-Schahn R, Zeidler C, Grimbacher B, Welte K, Klein C. A syndrome with congenital neutropenia and mutations in G6PC3. N Engl J Med. 2009 Jan 1;360(1):32-43. doi: 10.1056/NEJMoa0805051.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- 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.
David H McDermott, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Empagliflozin in people with Crohn's Disease and Glycogen Metabolism, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
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 9 inclusion and 8 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: finished, as of the sponsor's last update on 26 Jun 2025. 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 United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute Neutrophil Count (time frame: End of Treatment at 12 months). 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?
On the ClinicalTrials.gov record for NCT05078879, which also lists 3 linked publications.
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 26 Jun 2025.