Sodium Lactate Infusion in GLUT1DS Patients

Effects of Sodium Lactate Infusion in Patients With Glucose Transporter 1 Deficiency Syndrome (GLUT1DS)

This study investigates the effect of lactate infusion on epileptic discharges on EEG and seizure frequency in glucose transporter 1 deficiency syndrome (GLUT1DS) patients.

Study Overview

• Status: Completed
• Conditions: Epilepsy; Ketogenic Dieting; Lactic Acid Blood Increased; GLUT1DS1; GLUT1 Deficiency Syndrome; GLUT1DS2
• Intervention / Treatment: Other: sodiumlactate

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500GA
      • Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; three GLUT1DS patients with drug resistant epilepsy who tried the ketogenic diet without any benefits.	Other: sodiumlactate; intravenous sodiumlactate 600mmol/L

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of changes in epileptic discharges on EEG during the infusion of lactate.	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.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in seizure frequency clinical visible by caregivers during and after infusion of sodium lactate.	All subjects have frequent seizures, we want to see if these clinically visible seizures reduce during or after infusion with sodium lactate.	1 day
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
Concentration of potassium in blood during and after sodium lactate infusion		1 day
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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2022
• Primary Completion (Actual): November 18, 2022
• Study Completion (Actual): November 18, 2022

Study Registration Dates

• First Submitted: September 18, 2019
• First Submitted That Met QC Criteria: September 30, 2019
• First Posted (Actual): October 2, 2019

Study Record Updates

• Last Update Posted (Actual): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 22, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: epilepsy; GLUT1 deficiency syndrome; sodium lactate infusion
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease; Epilepsy; Syndrome; Hyperlactatemia
• Other Study ID Numbers: 109147

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: We want to include three patients, who all are there own control. If one of their EEGs shows interesting changes during or after lactate infusion, we plan to describe that in our article.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No