Glucose Transporter Type 1 Deficiency SyndromeNCT04137692
Red Blood Cell Exchange Transfusion as a Novel Treatment for GLUT1 Deficiency Syndrome
A study testing Red Blood Cell Transfusion in people with Glucose Transporter Type 1 Deficiency Syndrome and GLUT1DS1, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
Pathogenic mutations of the brain glucose transporter type I lead to glucose transporter deficiency syndrome (G1D), which is most often associated with medication-refractory epilepsy and movement dysfunction. Read more about this study
- Who is it for?
- Ages 16 to 80 years
- Conditions the study is for
- Glucose Transporter Type 1 Deficiency Syndrome, GLUT1DS1
- What is being tested?
- Red Blood Cell Transfusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2027to Aug 2031
- Phase
- Interventional
- 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 16 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or Female
- Age 16 years to 80 years old.
- Diagnosed with genetically confirmed glucose transporter type 1 disorder
- Patients not currently receiving ketogenic dietary therapy, due to failure of this diet to achieve seizure remission or due to patient preference, including compliance or tolerance issues.
- Subjects must be able to provide informed consent for themselves or have a parent or legally authorized representative (LAR) provide permission if the subject is a minor or lacks capacity to consent.
- Spanish and English speakers will be eligible for participation. Spanish-speaking participants may be enrolled, and the study team is equipped to conduct the consent process in Spanish. The Principal Investigator (PI) is fluent in Spanish and will conduct the consent process in Spanish when applicable.
- IHD-RBCx is determined to be a safe and appropriate procedure for the subject by the transfusion medicine physician based on clinical and laboratory assessment.
Who cannot join
- Currently on the ketogenic diet or taking triheptanoin (C7) oil
- No genetic confirmation of G1D diagnosis
- Unable to return for follow up visits
- Weak peripheral veins, such that IV placement is contraindicated (required for transfusion)
- Serious chronic medical conditions, such as congestive heart failure, renal failure, liver failure, or any other medical conditions that preclude large volume transfusions.
- Patients currently pregnant or breast-feeding are excluded from participating in this research. Patients who plan on getting pregnant during this research or who are unwilling to use birth control, including abstinence, during the course of this research are also excluded due to safety concerns for the fetus.
- An evaluation by the transfusion physician as to whether IHD-RBCx is a safe option will be part of the screening assessment. If IHD-RBCx is deemed unsafe based on laboratory parameters such as a low red blood cell count, then the subject will not be eligible to participate in this study.
Trial locations and contacts
1 site in 1 country.
About this study
Pathogenic mutations of the brain glucose transporter type I lead to glucose transporter deficiency syndrome (G1D), which is most often associated with medication-refractory epilepsy and movement dysfunction. At present, G1D is only alleviated by interventions such as the ketogenic diet, which can be poorly tolerated and afford only an incomplete restoration of neural function. A better understanding of G1D can uncover new fundamental aspects of brain function while facilitating the development of new therapies aimed to restore brain metabolism and excitability. We will conduct a mechanistic trial that will utilize a mechanism-testing framework broadly applicable to metabolic interventions. The trial will investigate red blood cell exchange (i.e., the replacement of human G1D circulating red cells, which are deficient in GLUT1) with healthy donor cells as a novel means to augment blood-to-brain glucose transport. The hypothesis is that electroencephalography post treatment will display an increase in beta brain activity. Additional measures of brain activity will also be secondarily tested.
Read the detailed description
Glucose Transporter 1 (GLUT1) is a protein that helps move glucose (sugar) into cells. Most tissues in the body have only small amounts of this protein. Red blood cells, however, have very large amounts of GLUT1, far more than they need for their own energy use. Because of this, red blood cells can take in and carry glucose at extremely high rates, much higher than they can actually use themselves. Some scientists believe that red blood cells may serve as a temporary storage system for glucose, especially when blood sugar levels are low. If this idea can be proven, it would change how we understand an important part of human biology.
This study may also lead to new treatment options for people with Glucose Transporter Type 1 Deficiency (G1D). G1D is a condition where the brain does not get enough glucose because the GLUT1 protein does not work properly. Right now, the only treatment is the ketogenic diet. This diet helps some patients with seizures, but it does not work well for long-term brain development or overall health, so better treatments are needed. It is usually believed that G1D mainly affects the cells in the brain's blood vessels, which help control what gets into the brain. However, many G1D patients also have low levels of GLUT1 in their red blood cells, meaning their red blood cells may not carry enough glucose. This may also play a role in the disease. Animal models, like mice with GLUT1 deficiency, do not accurately mimic the human condition, so they cannot fully answer this question. Red blood cell exchange (RBCx) is already used safely and at reasonable cost for patients with sickle cell disease to prevent strokes and blood vessel problems. Because RBCx replaces a person's red blood cells with donor cells, it could be a promising new approach for treating G1D.
- Being tested
- Red Blood Cell Transfusion
- Keywords
- G1D, Glucose transporter
- Medical subject headings
- Glut1 Deficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Red Blood Cell TransfusionOther
The procedure will be performed as an outpatient according to protocols established for sickle cell anemia patients. Two IVs are placed for the purposes of transfusion, one for draw and one for return. Patients will undergo isovolemic hemodilution-red cell exchange (IHD- RBCx) with up to 10 units of red cell antigens (Rh group, Kell, Duffy, Kidd blood group antigens) matched normal donor red cells to replace a target of 70% of the patient's red cells with donor red cells.Total time of procedure: approximately 150 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Red Blood Cell Transfusion | Experimental | Patients will undergo isovolemic hemodilution-red cell exchange (IHD- RBCx) with up to 10 units of red cell antigens (Rh group, Kell, Duffy, Kidd blood group antigens) matched normal donor red cells to replace a target of 70% of the patient's red cells with donor red cells. Receives: Other: Red Blood Cell Transfusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in electroencephalography (EEG) measures during transfusion.
Electroencephalography measures number of seizures recorded during the transfusion. Number of seizures will be assessed using standard observation of the electroencephalogram (EEG).
Measured: Baseline: During Transfusion
Change from baseline in electroencephalography (EEG) measures 60 days after transfusion.
Electroencephalography measures number of seizures recorded 60 days after the transfusion. Number of seizures will be assessed using standard observation of the electroencephalogram (EEG).
Measured: Baseline - 60 Days After Transfusion
Secondary outcomes (9)
Change from baseline in Peabody Picture Vocabulary Test (PPVT) standard scores immediately after transfusion
The Peabody Picture Vocabulary Test (PPVT) measures receptive vocabulary skills. Total scores range from 20 to 160, with higher scores indicating stronger receptive language ability.
Measured: Baseline - Immediately after transfusion
Change from baseline in Peabody Picture Vocabulary Test (PPVT) standard scores 60 days after transfusion
The Peabody Picture Vocabulary Test (PPVT) measures receptive vocabulary skills. Total scores range from 20 to 160, with higher scores indicating stronger receptive language ability.
Measured: Baseline - 60 days after transfusion
Change from baseline in Expressive Vocabulary Test (EVT) standard scores immediately after transfusion
The Expressive Vocabulary Test (EVT) evaluates expressive vocabulary and word retrieval abilities. Total Standard scores typically range from 20 to 160, with higher scores indicating stronger expressive language skills.
Measured: Baseline - Immediately after transfusion
Change from baseline in Expressive Vocabulary Test (EVT) standard scores 60 days after transfusion
The Expressive Vocabulary Test (EVT) evaluates expressive vocabulary and word retrieval abilities. Total Standard scores typically range from 20 to 160, with higher scores indicating stronger expressive language skills.
Measured: Baseline - 60 days after transfusion
Change from Baseline in T-scores on the Connors Continuous Performance Test Immediately After Transfusion
T-scores will be obtained from the Connors Continuous Performance Test (CPT). Minimum T-score is <30 and maximum is 90. For the Hit Reaction Time domain, higher T-scores indicate slower reaction time. For detectability, omissions, commissions, and perseverations, higher T-scores indicate elevated performance.
Measured: Baseline - Immediately after transfusion
Change from Baseline in T-scores on the Connors Continuous Performance Test 60 Days After Transfusion
T-scores will be obtained from the Connors Continuous Performance Test (CPT). Minimum T-score is <30 and maximum is 90. For the Hit Reaction Time domain, higher T-scores indicate slower reaction time. For detectability, omissions, commissions, and perseverations, higher T-scores indicate elevated performance.
Measured: Baseline - 60 days after transfusion
Number of participants immediately after transfusion with erythrocyte Glut1 levels increased by over 40% from baseline
Baseline erythrocyte Glut1 levels are used as the reference point. This measure captures the number of participants whose Glut1 levels increase by more than 40% immediately after transfusion compared to their baseline value.
Measured: Immediately after transfusion
Number of participants 60 days after transfusion with erythrocyte Glut1 levels increased by over 40% from baseline
Baseline erythrocyte Glut1 levels are used as the reference point. This measure captures the number of participants whose Glut1 levels increase by more than 40% 60 days after transfusion compared to their baseline value.
Measured: 60 days after transfusion
Change from Baseline in General Medical & Neurological Examination 60 Days After Transfusion
This measure assesses change from baseline in the standardized clinical physical examination, which includes 12 domains scored as normal or abnormal. Minimum total score is 0. Maximum total score is 76. Higher total scores indicate a more normal examination and better outcomes, while lower scores indicate more abnormalities.
Measured: Baseline - 60 days after transfusion
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 startSep 2027 (estimated)
- Primary completionAug 2030 (estimated)
- Study completionAug 2031 (estimated)
Why it stopped: PI is transferring institutions.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Glucose Transporter Type 1 Deficiency SyndromeStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe 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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Juan Pascual, MD, PhD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04137692
- Sponsor's protocol ID
- 24-07027753
- Other IDs
- RM1NS133593
- Status last verified
- Dec 2025
- First submitted
- 8 Oct 2019
- Last updated
- 11 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Publications
Lee EE, Ma J, Sacharidou A, Mi W, Salato VK, Nguyen N, Jiang Y, Pascual JM, North PE, Shaul PW, Mettlen M, Wang RC. A Protein Kinase C Phosphorylation Motif in GLUT1 Affects Glucose Transport and is Mutated in GLUT1 Deficiency Syndrome. Mol Cell. 2015 Jun 4;58(5):845-53. doi: 10.1016/j.molcel.2015.04.015. Epub 2015 May 14.
PubMed 25982116Wang RC, Lee EE, De Simone N, Kathote G, Primeaux S, Avila A, Yu DM, Johnson M, Good LB, Jakkamsetti V, Sarode R, Holland AA, Pascual JM. Red blood cells as glucose carriers to the human brain: Modulation of cerebral activity by erythrocyte exchange transfusion in Glut1 deficiency (G1D). J Cereb Blood Flow Metab. 2023 Mar;43(3):357-368. doi: 10.1177/0271678X221146121. Epub 2022 Dec 15.
PubMed 36523131
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Red Blood Cell Exchange Transfusion as a Novel Treatment for GLUT1 Deficiency Syndrome
- ClinicalTrials.gov ID
- NCT04137692
- Acronym / sponsor ID
- 24-07027753
- Keywords
- G1D, Glucose transporter
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: PI is transferring institutions.
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Sep 2027 (estimated)
- Primary completion
- Aug 2030 (estimated)
- Study completion
- Aug 2031 (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.
Pathogenic mutations of the brain glucose transporter type I lead to glucose transporter deficiency syndrome (G1D), which is most often associated with medication-refractory epilepsy and movement dysfunction. At present, G1D is only alleviated by interventions such as the ketogenic diet, which can be poorly tolerated and afford only an incomplete restoration of neural function. A better understanding of G1D can uncover new fundamental aspects of brain function while facilitating the development of new therapies aimed to restore brain metabolism and excitability. We will conduct a mechanistic trial that will utilize a mechanism-testing framework broadly applicable to metabolic interventions. The trial will investigate red blood cell exchange (i.e., the replacement of human G1D circulating red cells, which are deficient in GLUT1) with healthy donor cells as a novel means to augment blood-to-brain glucose transport. The hypothesis is that electroencephalography post treatment will display an increase in beta brain activity. Additional measures of brain activity will also be secondarily tested.
Detailed description
Glucose Transporter 1 (GLUT1) is a protein that helps move glucose (sugar) into cells. Most tissues in the body have only small amounts of this protein. Red blood cells, however, have very large amounts of GLUT1, far more than they need for their own energy use. Because of this, red blood cells can take in and carry glucose at extremely high rates, much higher than they can actually use themselves. Some scientists believe that red blood cells may serve as a temporary storage system for glucose, especially when blood sugar levels are low. If this idea can be proven, it would change how we understand an important part of human biology.
This study may also lead to new treatment options for people with Glucose Transporter Type 1 Deficiency (G1D). G1D is a condition where the brain does not get enough glucose because the GLUT1 protein does not work properly. Right now, the only treatment is the ketogenic diet. This diet helps some patients with seizures, but it does not work well for long-term brain development or overall health, so better treatments are needed. It is usually believed that G1D mainly affects the cells in the brain's blood vessels, which help control what gets into the brain. However, many G1D patients also have low levels of GLUT1 in their red blood cells, meaning their red blood cells may not carry enough glucose. This may also play a role in the disease. Animal models, like mice with GLUT1 deficiency, do not accurately mimic the human condition, so they cannot fully answer this question. Red blood cell exchange (RBCx) is already used safely and at reasonable cost for patients with sickle cell disease to prevent strokes and blood vessel problems. Because RBCx replaces a person's red blood cells with donor cells, it could be a promising new approach for treating G1D.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Red Blood Cell Transfusion | Experimental | Other: Red Blood Cell TransfusionPatients will undergo isovolemic hemodilution-red cell exchange (IHD- RBCx) with up to 10 units of red cell antigens (Rh group, Kell, Duffy, Kidd blood group antigens) matched normal donor red cells to replace a target of 70% of the patient's red cells with donor red cells. |
Who may qualify
- Ages
- 16 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Male or Female
- Age 16 years to 80 years old.
- Diagnosed with genetically confirmed glucose transporter type 1 disorder
- Patients not currently receiving ketogenic dietary therapy, due to failure of this diet to achieve seizure remission or due to patient preference, including compliance or tolerance issues.
- Subjects must be able to provide informed consent for themselves or have a parent or legally authorized representative (LAR) provide permission if the subject is a minor or lacks capacity to consent.
Key exclusion criteria (7 listed)
- Currently on the ketogenic diet or taking triheptanoin (C7) oil
- No genetic confirmation of G1D diagnosis
- Unable to return for follow up visits
- Weak peripheral veins, such that IV placement is contraindicated (required for transfusion)
- Serious chronic medical conditions, such as congestive heart failure, renal failure, liver failure, or any other medical conditions that preclude large volume transfusions.
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 |
|---|---|---|
| Red Blood Cell TransfusionThe procedure will be performed as an outpatient according to protocols established for sickle cell anemia patients. Two IVs are placed for the purposes of transfusion, one for draw and one for return. Patients will undergo isovolemic hemodilution-red cell exchange (IHD- RBCx) with up to 10 units of red cell antigens (Rh group, Kell, Duffy, Kidd blood group antigens) matched normal donor red cells to replace a target of 70% of the patient's red cells with donor red cells.Total time of procedure: approximately 150 minutes. | Other | Red Blood Cell Transfusion |
Primary outcome
Change from baseline in electroencephalography (EEG) measures during transfusion.
Time frame: Baseline: During Transfusion
Electroencephalography measures number of seizures recorded during the transfusion. Number of seizures will be assessed using standard observation of the electroencephalogram (EEG).
Change from baseline in electroencephalography (EEG) measures 60 days after transfusion.
Time frame: Baseline - 60 Days After Transfusion
Electroencephalography measures number of seizures recorded 60 days after the transfusion. Number of seizures will be assessed using standard observation of the electroencephalogram (EEG).
9 secondary outcomes
Change from baseline in Peabody Picture Vocabulary Test (PPVT) standard scores immediately after transfusion
Time frame: Baseline - Immediately after transfusion
Change from baseline in Peabody Picture Vocabulary Test (PPVT) standard scores 60 days after transfusion
Time frame: Baseline - 60 days after transfusion
Change from baseline in Expressive Vocabulary Test (EVT) standard scores immediately after transfusion
Time frame: Baseline - Immediately after transfusion
Change from baseline in Expressive Vocabulary Test (EVT) standard scores 60 days after transfusion
Time frame: Baseline - 60 days after transfusion
Change from Baseline in T-scores on the Connors Continuous Performance Test Immediately After Transfusion
Time frame: Baseline - Immediately after transfusion
Change from Baseline in T-scores on the Connors Continuous Performance Test 60 Days After Transfusion
Time frame: Baseline - 60 days after transfusion
Number of participants immediately after transfusion with erythrocyte Glut1 levels increased by over 40% from baseline
Time frame: Immediately after transfusion
Number of participants 60 days after transfusion with erythrocyte Glut1 levels increased by over 40% from baseline
Time frame: 60 days after transfusion
Change from Baseline in General Medical & Neurological Examination 60 Days After Transfusion
Time frame: Baseline - 60 days after transfusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2025.
- Background: PubMed 25982116Lee EE, Ma J, Sacharidou A, Mi W, Salato VK, Nguyen N, Jiang Y, Pascual JM, North PE, Shaul PW, Mettlen M, Wang RC. A Protein Kinase C Phosphorylation Motif in GLUT1 Affects Glucose Transport and is Mutated in GLUT1 Deficiency Syndrome. Mol Cell. 2015 Jun 4;58(5):845-53. doi: 10.1016/j.molcel.2015.04.015. Epub 2015 May 14.
- Derived from this study: PubMed 36523131Wang RC, Lee EE, De Simone N, Kathote G, Primeaux S, Avila A, Yu DM, Johnson M, Good LB, Jakkamsetti V, Sarode R, Holland AA, Pascual JM. Red blood cells as glucose carriers to the human brain: Modulation of cerebral activity by erythrocyte exchange transfusion in Glut1 deficiency (G1D). J Cereb Blood Flow Metab. 2023 Mar;43(3):357-368. doi: 10.1177/0271678X221146121. Epub 2022 Dec 15.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
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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.
Juan Pascual, MD, PhD principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Red Blood Cell Transfusion in people with Glucose Transporter Type 1 Deficiency Syndrome and GLUT1DS1, run by Weill Medical College of Cornell University 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 7 inclusion and 7 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: paused, as of the sponsor's last update on 11 Dec 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.
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?
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?
Change from baseline in electroencephalography (EEG) measures during transfusion. (time frame: Baseline: During Transfusion). 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 NCT04137692, which also lists 2 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 11 Dec 2025; AzTrials last refreshed its copy on 7 Nov 2026.