Red Blood Cell Exchange Transfusion as a Novel Treatment for GLUT1 Deficiency Syndrome

NCT04137692 | Suspended DMC

• 2 other identifiers: 24-07027753RM1NS133593
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Glucose Transporter Type 1 Deficiency Syndrome; GLUT1DS1

Keywords

G1D; Glucose transporter

Outcome Measures

Primary Outcomes (2)

• 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).

  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).

  Baseline - 60 Days After Transfusion

Secondary Outcomes (9)

• Change from baseline in Peabody Picture Vocabulary Test (PPVT) standard scores immediately after transfusion

  Baseline - Immediately after transfusion

• Change from baseline in Peabody Picture Vocabulary Test (PPVT) standard scores 60 days after transfusion

  Baseline - 60 days after transfusion

• Change from baseline in Expressive Vocabulary Test (EVT) standard scores immediately after transfusion

  Baseline - Immediately after transfusion

• Change from baseline in Expressive Vocabulary Test (EVT) standard scores 60 days after transfusion

  Baseline - 60 days after transfusion

• Change from Baseline in T-scores on the Connors Continuous Performance Test Immediately After Transfusion

  Baseline - Immediately after transfusion

Study Arms (1)

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.

Other: Red Blood Cell Transfusion

Interventions

Red Blood Cell Transfusion OTHER

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.

Red Blood Cell Transfusion

Eligibility Criteria

• Age: 16 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Related Publications (2)

• 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.

  PMID: 25982116 BACKGROUND

• Wang 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.

  PMID: 36523131 DERIVED

MeSH Terms

Conditions

Glut1 Deficiency Syndrome

Interventions

Erythrocyte Transfusion

Intervention Hierarchy (Ancestors)

Blood Component Transfusion; Blood Transfusion; Biological Therapy; Therapeutics

Study Officials

• Juan Pascual, MD, PhD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2019
• First Posted: October 24, 2019
• Study Start (Estimated): September 1, 2027
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2031
• Last Updated: December 11, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose.

Locations

US (1)