E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
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E.1.1.1 | Medical condition in easily understood language |
GLUT1DS is a genetic syndrome characterized by developmental problems, movement disorders and severe epilepsy. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of this explorative study is to investigate whether treatment with lactate has a positive effect on the drug-resistant epilepsy and EEG of patients with GLUT1DS.
The primary objective is to assess changes in EEG during and shortly after infusion of lacate. |
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E.2.2 | Secondary objectives of the trial |
To assess any changes in seizure frequency during and shortly after infusion of lactate.
To assess any change in laboratory parameters during infusion and shortly after: lactate, pH, sodium, bicarbonate, chloride, potassium, glucose
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be eligible to participate in this study, a subject must meet all of the following 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 but without beneficial effects.
- Age > 6 years.
- Informed consent. |
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E.4 | Principal exclusion criteria |
A potential subject who meets any of the following criteria will be excluded from participation in this study:
- 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in frequency or form of epileptic discharges on EEG during of shortly after infusion of sodiumlactate.
The change in EEG will be measured by a neurologist experienced in reading EEG’s
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
EEG will be continuously registered during the experiment. |
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E.5.2 | Secondary end point(s) |
Seizure frequency: Subjects will be recorded on video camera and seizures will be monitored and counted by researchers and parents/caregivers.
Laboratory measures: All measurements will be performed in blood samples, and all samples will be analysed in laboratories of the Radboudumc.
- lactate concentration
- pH
- glucose
- sodium
- potassium
- chloride
- bicarbonate
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Seizure frequency: Subjects will be monitored continuously during the experiment.
Laboratory measures: T-60, T10, T20, T40, T60, T100, T120, T140, T200 and T240 minutes. Blood samples will be stopped earlier if all values have returned to baseline before the end of the experiment. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Single center, interventional, explorative, open label, proof of principle study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Each subject baseline characteristics are control of the subject. |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | 1 |