Epilepsy, GLUT1 Deficiency Syndrome, GLUT1DS1, GLUT1DS2, Ketogenic Dieting, Lactic Acid Blood Increased
Conditions
Keywords
GLUT1 deficiency syndrome, sodium lactate infusion, epilepsy
Brief summary
This study investigates the effect of lactate infusion on epileptic discharges on EEG and seizure frequency in glucose transporter 1 deficiency syndrome (GLUT1DS) patients.
Detailed description
In glucose transporter 1 deficiency syndrome (GLUT1DS) cerebral glucose uptake from the systemic blood circulation is limited, because of deficient transport of glucose across the blood-brain barrier by the transporter protein (GLUT1). Classically patients present with developmental problems, movement disorders and severe epilepsy. There is no curative treatment for GLUT1DS, and anti-epileptic drugs usually have little to no effect. The ketogenic diet, providing ketones as an alternative energy substrate for the brain is an effective treatment option for the epilepsy and movement disorders in many GLUT1DS patients. Unfortunately, not in all GLUT1DS patients the ketogenic diet has a positive effect and other treatment options for these patients are very limited. Traditionally, lactate is seen as a waste product of glycolysis during anaerobic conditions and a marker of ischemia. Interestingly, research has shown the beneficial side of lactate as an energy source for different organs. It seems that the brain can indeed use lactate as an alternative energy metabolite, besides glucose and ketones. The aim of this study is to investigate whether lactate can be an alternative energy metabolite in the GLUT1DS brain, and reduce epileptic discharges on EEG when intravenously administered in patients with GLUT1DS.
Interventions
OTHERsodiumlactate
intravenous sodiumlactate 600mmol/L
Sponsors
Radboud University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single center, interventional, explorative, open label, proof of principle study
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with GLUT1DS and known in our center. * Baseline characteristics include a high frequency of clinical seizures and epileptic discharges on EEG. * History of trying ketogenic diet with good compliance without beneficial effects. * Age \> 6 years. * Informed consent.
Exclusion criteria
* Additional medical condition or illness that impairs the patient's ability to participate in the study (for example actual treatment of a malignancy, active infection, poorly controlled diabetes mellitus, hypertension, organ failure, clinically significant haematological or biochemical abnormalities). * Elevated serum sodium (\> 145 mmol/L). * Participation in another interventional study at start of the study or during the study. * Presence of known panic disorders or a history of panic attacks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of changes in epileptic discharges on EEG during the infusion of lactate. | 1 day | All subjects have frequent epileptic discharges on EEG. We want to objectify the change in epileptic discharges on EEG during and after the infusion of sodium lactate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of lactate in blood during and after sodium lactate infusion | 1 day | — |
| Concentration of glucose in blood during and after sodium lactate infusion | 1 day | — |
| Concentration of sodium in blood during and after sodium lactate infusion | 1 day | — |
| Change in seizure frequency clinical visible by caregivers during and after infusion of sodium lactate. | 1 day | All subjects have frequent seizures, we want to see if these clinically visible seizures reduce during or after infusion with sodium lactate. |
| Concentration of bicarbonate in blood during and after sodium lactate infusion | 1 day | — |
| Concentration of chloride in blood during and after sodium lactate infusion | 1 day | — |
| pH in blood during and after sodium lactate infusion | 1 day | — |
| Concentration of potassium in blood during and after sodium lactate infusion | 1 day | — |
Countries
Netherlands
Outcome results
None listed