Glut1 Deficiency, GLUT1DS1
Conditions
Keywords
GLUT1 Deficiency, GLUT1 Deficiency Syndrome, GLUT1DS, SLC2A1, Fucose, L-fucose
Brief summary
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
DRUGL-fucose
L-fucose will be administered as 500 mg/kg to a maximum of 10 g three times per day by mouth.
OTHERPlacebo
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.
Sponsors
Oregon Health and Science University
Glut1 Deficiency Foundation
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years 2. 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) 3. Presence of ataxia
Exclusion criteria
1. Inability to swallow liquids 2. Change in neurological medications (either medication itself or medication dosages) in the past 90 days 3. Use of fucose- or mannose-containing supplements within one year of enrollment 4. 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): 1. Any degree of hepatic impairment based on the Child-Pugh classification 2. eGFR (as measured by serum creatinine or cystatin C) \< 60 mg/min/1.73m2 3. Hemoglobin A1c \> 6.5% 4. Hemoglobin level below the lower limit of normal (LLN) for sex and age 5. Platelet counts below the LLN for sex and age 5. Subjects who are pregnant, breastfeeding, or planning to become pregnant within one year of enrollment 6. Enrollment in an investigational new drug trial for G1DS within one year of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety labs: serum calcium | 24 weeks | Changes in serum calcium (Ca) measured as mmol/L |
| Safety labs: serum bicarbonate | 24 weeks | Changes in serum bicarbonate/carbonate measured as mmol/L |
| Subject-reported adverse events | 24 weeks | Rate and character (including standardized severity) of adverse events as reported by the study subjects |
| SARA (Scale for the Assessment and Rating of Ataxia) Score | 24 weeks | Severity of ataxia and cerebellar involvement as measured by the SARA clinical scales. This score ranges from 0 (no ataxia) to 40 (most severe ataxia) |
| Modified SARA (Scale for the Assessment and Rating of Ataxia) score | 24 weeks | This modified score suggested by the FDA rates severity of ataxia from 0 (no ataxia) to 16 (most severe ataxia) |
| ICARS (International Cooperative Ataxia Rating Scale) Score | 24 weeks | This scale score the severity of ataxia and other cerebellar findings from 0 (no compromise) to 100 (maximal impairment) |
| Safety labs: hemoglobin | 24 weeks | Changes in levels of hemoglobin in g/dL |
| Safety labs: white blood cell count | 24 weeks | Changes in white blood cell counts as measured in cells/mm3 |
| Safety labs: platelet count | 24 weeks | Changes in platelet counts measured as cells/mm3 |
| Safety labs: lactate dehydrogenase | 24 weeks | Changes in lactate dehydrogenase (LDH) levels measured as U/L |
| Safety labs: alanine-aminotransferase | 24 weeks | Changes in alanine-aminotransferase (ALT) measured as U/L |
| Safety labs: aspartate-aminotransferase | 24 weeks | Changes in aspartate-aminotransferase (AST) measured as U/L |
| Safety labs: gamma-glutamyltransferase | 24 weeks | Changes in gamma-glutamyltransferase (GGT) measured as U/L |
| Safety labs: serum creatinine | 24 weeks | Changes in serum creatinine measured as mg/dL |
| Safety labs: blood urea nitrogen | 24 weeks | Changes in blood urea nitrogen (BUN) measured as mg/dL |
| Safety labs: serum sodium | 24 weeks | Changes in serum sodium (Na) as measured in mmol/L |
| Safety labs: serum potassium | 24 weeks | Changes in serum potassium (K) measured as mmol/L |
| Safety labs: serum chloride | 24 weeks | Changes in serum chloride (Cl) measured as mmol/L |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of paroxysmal exercise-induced dystonia | 24 weeks | Frequency of paroxysmal exercise-induced dystonic episodes, captured at a diary for 1 week, at the last week of each study arm. |
| Patient-Reported Outcomes Measurement Information System (PROMIS) score | 24 weeks | Objective and quantitative measurement of quality of life using the PROMIS Fatigue, Mobility, and Physical Function tool |
| Frequency of seizures | 24 weeks | Frequency and duration of seizures captured at a diary for 1 week, at the last week of each study arm. |
| Severity of dysarthria | 24 weeks | Number of "PA-TA" repetitions over 10 seconds ("PATA Rate Test") |
| Frequency and severity of migraines | 24 weeks | Frequency and severity of migraines captured at a diary for 1 week, at the last week of each study arm. |
| World Health Organization Quality of Life (WHO-QoL) scale | 24 weeks | Objective scoring of global and domain-specific quality of life with the World Health Organization Quality of Life (WHO-QoL) scale. |
Countries
United States
Contacts
CONTACTCelena Byerlee-Dixon
STUDY_DIRECTORRodrigo T. Starosta, MD, PhD
Oregon Health and Science University
Outcome results
None listed