A Phase II Study With Exploratory Outcomes of Fucose Supplementation in GLUT1 Deficiency Syndrome

Official title

A Phase II Randomized, Double-blind, Placebo-controlled, Cross-over Study With Exploratory Outcomes of Fucose Supplementation in GLUT1 Deficiency Syndrome

Overview

This is a single-center, randomized, double-blind, placebo-controlled, cross-over study to evaluate the efficacy and safety of L-fucose supplementation in subjects with GLUT1 deficiency syndrome (GLUT1DS).

Interventions

• Drug L-fucose
  L-fucose will be administered as 500 mg/kg to a maximum of 10 g three times per day by mouth.
• Other Placebo
  Placebo will be composed of micro-cellulose powder with a small amount of Stevia for taste mimicking, to be taken at 500 mg/kg for a maximum of 10 g three times per day by mouth.

Primary outcome measures

• SARA (Scale for the Assessment and Rating of Ataxia) Score [Time frame: 24 weeks]
• Modified SARA (Scale for the Assessment and Rating of Ataxia) score [Time frame: 24 weeks]
• ICARS (International Cooperative Ataxia Rating Scale) Score [Time frame: 24 weeks]
• Safety labs: hemoglobin [Time frame: 24 weeks]
• Safety labs: white blood cell count [Time frame: 24 weeks]
• Safety labs: platelet count [Time frame: 24 weeks]
• Safety labs: lactate dehydrogenase [Time frame: 24 weeks]
• Safety labs: alanine-aminotransferase [Time frame: 24 weeks]
• Safety labs: aspartate-aminotransferase [Time frame: 24 weeks]
• Safety labs: gamma-glutamyltransferase [Time frame: 24 weeks]

Secondary outcome measures (6)

• Severity of dysarthria [Time frame: 24 weeks]
• Frequency and severity of migraines [Time frame: 24 weeks]
• Frequency of paroxysmal exercise-induced dystonia [Time frame: 24 weeks]
• Frequency of seizures [Time frame: 24 weeks]
• World Health Organization Quality of Life (WHO-QoL) scale [Time frame: 24 weeks]
• Patient-Reported Outcomes Measurement Information System (PROMIS) score [Time frame: 24 weeks]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Confirmed diagnosis of GLUT1DS, including at least 2 out of the following 3: molecular genetic testing showing a pathogenic or likely pathogenic variant in SLC2A1; documented hypoglycorrhachia with a CSF:blood glucose ratio ≤ 0.6; clinical features consistent with GLUT1DS (epilepsy, movement disorders, ataxia, intellectual disability, dysarthria)
• Presence of ataxia

Exclusion criteria

• Inability to swallow liquids
• Change in neurological medications (either medication itself or medication dosages) in the past 90 days
• Use of fucose- or mannose-containing supplements within one year of enrollment
• Presence of hepatic, renal, hematological, or concomitant metabolic disorders, as assessed by the presence of a previous diagnosis of such disorders (for instance, chronic kidney disease, liver cirrhosis, diabetes mellitus) or by the following laboratory values, which will be considered if obtained clinically up to 90 days before enrollment (if this is not available, laboratory tests will be obtained prior to first study visit):

• Any degree of hepatic impairment based on the Child-Pugh classification
• eGFR (as measured by serum creatinine or cystatin C) < 60 mg/min/1.73m2
• Hemoglobin A1c > 6.5%
• Hemoglobin level below the lower limit of normal (LLN) for sex and age
• Platelet counts below the LLN for sex and age
• Subjects who are pregnant, breastfeeding, or planning to become pregnant within one year of enrollment
• Enrollment in an investigational new drug trial for G1DS within one year of enrollment

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Oregon Health and Science University — Portland

Identifiers

NCT: NCT07432490 · 00028024

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗