Red Blood Cell Exchange Transfusion as a Novel Treatment for GLUT1 Deficiency Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 暂停
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Change from baseline in electroencephalography (EEG) measures during transfusion.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Change from baseline in electroencephalography (EEG) measures during transfusion.
时间窗: 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.
时间窗: 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).
次要结局
- 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)
- Change from Baseline in T-scores on the Connors Continuous Performance Test 60 Days After Transfusion(Baseline - 60 days after transfusion)
- Number of participants immediately after transfusion with erythrocyte Glut1 levels increased by over 40% from baseline(Immediately after transfusion)
- Number of participants 60 days after transfusion with erythrocyte Glut1 levels increased by over 40% from baseline(60 days after transfusion)
- Change from Baseline in General Medical & Neurological Examination 60 Days After Transfusion(Baseline - 60 days after transfusion)