Red Blood Cell Transfusion for Glut1 Deficiency Syndrome

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Juan Pascual

Must not be taking: Ketogenic diet, Triheptanoin

Disqualifiers: No G1D diagnosis, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 1 day

5 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on the ketogenic diet or taking triheptanoin (C7) oil.

Is red blood cell transfusion generally safe for humans?

Red blood cell transfusions can be safe, but there are risks, especially if the blood has certain deficiencies like glucose-6-phosphate dehydrogenase (G6PD) deficiency, which can cause red blood cells to break down. Adverse reactions can occur, such as hemolysis (destruction of red blood cells) and other complications, particularly in children and infants. ^{1 2 3 4 5}

How is Red Blood Cell Exchange Transfusion different from other treatments for Glut1 Deficiency Syndrome?

Red Blood Cell Exchange Transfusion is unique because it involves replacing a patient's red blood cells with donor cells, which can help manage conditions by reducing iron accumulation and controlling abnormal red blood cell populations. This method is different from simple transfusions and is often used in conditions like sickle cell disease, but its application in Glut1 Deficiency Syndrome is novel and not well-studied. ^{1 2 6 7 8}

What is the purpose of this trial?

This proposal is an investigator-initiated, single-site proof of concept trial. Five 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. The procedure will be performed as an outpatient according to protocols established for sickle cell anemia patients. One of the investigators is an expert on RBCx and will oversee the transfusion. Subjects will be assessed before and after transfusion, and at two months post transfusion. Outcome measures include neurological exam, electroencephalography (EEG), neuropsychological testing, and biochemical assays.

Research Team

Juan Pascual, MD, PhD

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

This trial is for individuals aged 16-64 with genetically confirmed GLUT1 Deficiency Syndrome who are not on dietary therapies like the ketogenic diet due to ineffectiveness or personal choice. They must be able to return for follow-ups and have good veins for IV placement. Pregnant or breastfeeding individuals, those planning pregnancy without birth control, and patients with serious chronic conditions are excluded.

Inclusion Criteria

I have been diagnosed with a genetic glucose transporter type 1 disorder.

I am between 16 and 64 years old.

I am either male or female.

Exclusion Criteria

I am currently following a ketogenic diet or taking C7 oil.

I do not have serious conditions like heart, kidney, or liver failure.

My condition has not been genetically confirmed as G1D.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo isovolemic hemodilution-red cell exchange (IHD-RBCx) with up to 10 units of matched donor red cells

1 day

1 visit (in-person)

Immediate Post-Treatment Assessment

Participants are assessed immediately after transfusion for changes in neuropsychological and biochemical measures

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neurological exams and EEG

8 weeks

1 visit (in-person) at 60 days post-transfusion

Treatment Details

Interventions

• Red Blood Cell Exchange Transfusion

Trial Overview The study tests if a red blood cell exchange transfusion can treat GLUT1 Deficiency Syndrome. Five patients will receive matched donor red cells aiming to replace 70% of their own red cells. The procedure follows protocols used in sickle cell anemia treatment and includes pre- and post-transfusion assessments plus two-month follow-up exams.

Participant Groups

Group I: Red Blood Cell Transfusion Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Juan Pascual

Lead Sponsor

Trials

5

Recruited

30+

Findings from Research

In a study analyzing 149,052 units of transfused red blood cells (RBCs) over 5.5 years, irradiated RBCs were found to significantly increase the frequency of non-allergic transfusion reactions, with an odds ratio of 1.89.

Prolonged storage of irradiated RBCs was specifically linked to a higher incidence of these non-allergic reactions, suggesting that both irradiation and storage duration may impact the safety of RBC transfusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irradiation and prolonged storage of red cells are associated with increased adverse events. Chen, J., Biller, E., Losos, M., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Glucose-6-phosphate dehydrogenase deficiency in transfusion medicine: the unknown risks. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Posttransfusional hemolysis in recipients of glucose-6-phosphate dehydrogenase-deficient erythrocytes. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Acquired hemoglobin variants and exposure to glucose-6-phosphate dehydrogenase deficient red blood cell units during exchange transfusion for sickle cell disease in a patient requiring antigen-matched blood. [2014]

4. England pubmed.ncbi.nlm.nih.gov

Irradiation and prolonged storage of red cells are associated with increased adverse events. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Adverse outcomes of blood transfusion in children: analysis of UK reports to the serious hazards of transfusion scheme 1996-2005. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Donor blood glucose 6-phosphate dehydrogenase deficiency reduces the efficacy of exchange transfusion in neonatal hyperbilirubinemia. [2013]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Red Blood Cells: Exchange, Transfuse, or Deplete. [2020]

8. Germany pubmed.ncbi.nlm.nih.gov

Acute intravascular haemolysis following exchange transfusion with G-6-PD deficient blood. [2019]