A Phase II Randomized, Double-blind, Placebo-controlled, Cross-over Study With Exploratory Outcomes of Fucose Supplementation in GLUT1 Deficiency Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- SARA (Scale for the Assessment and Rating of Ataxia) Score
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
L-fucose followed by placebo
L-fucose for 12 weeks, followed by placebo for 12 weeks.
干预措施: Placebo (Other)
Placebo followed by L-fucose
Placebo for 12 weeks, followed by L-fucose for 12 weeks.
干预措施: Placebo (Other)
L-fucose followed by placebo
L-fucose for 12 weeks, followed by placebo for 12 weeks.
干预措施: L-fucose (Drug)
Placebo followed by L-fucose
Placebo for 12 weeks, followed by L-fucose for 12 weeks.
干预措施: L-fucose (Drug)
结局指标
主要结局
SARA (Scale for the Assessment and Rating of Ataxia) Score
时间窗: 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
时间窗: 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
时间窗: 24 weeks
This scale score the severity of ataxia and other cerebellar findings from 0 (no compromise) to 100 (maximal impairment)
Safety labs: hemoglobin
时间窗: 24 weeks
Changes in levels of hemoglobin in g/dL
Safety labs: white blood cell count
时间窗: 24 weeks
Changes in white blood cell counts as measured in cells/mm3
Safety labs: platelet count
时间窗: 24 weeks
Changes in platelet counts measured as cells/mm3
Safety labs: lactate dehydrogenase
时间窗: 24 weeks
Changes in lactate dehydrogenase (LDH) levels measured as U/L
Safety labs: alanine-aminotransferase
时间窗: 24 weeks
Changes in alanine-aminotransferase (ALT) measured as U/L
Safety labs: aspartate-aminotransferase
时间窗: 24 weeks
Changes in aspartate-aminotransferase (AST) measured as U/L
Safety labs: gamma-glutamyltransferase
时间窗: 24 weeks
Changes in gamma-glutamyltransferase (GGT) measured as U/L
Safety labs: serum creatinine
时间窗: 24 weeks
Changes in serum creatinine measured as mg/dL
Safety labs: blood urea nitrogen
时间窗: 24 weeks
Changes in blood urea nitrogen (BUN) measured as mg/dL
Safety labs: serum sodium
时间窗: 24 weeks
Changes in serum sodium (Na) as measured in mmol/L
Safety labs: serum potassium
时间窗: 24 weeks
Changes in serum potassium (K) measured as mmol/L
Safety labs: serum chloride
时间窗: 24 weeks
Changes in serum chloride (Cl) measured as mmol/L
Safety labs: serum calcium
时间窗: 24 weeks
Changes in serum calcium (Ca) measured as mmol/L
Safety labs: serum bicarbonate
时间窗: 24 weeks
Changes in serum bicarbonate/carbonate measured as mmol/L
Subject-reported adverse events
时间窗: 24 weeks
Rate and character (including standardized severity) of adverse events as reported by the study subjects
次要结局
- Severity of dysarthria(24 weeks)
- Frequency and severity of migraines(24 weeks)
- Frequency of paroxysmal exercise-induced dystonia(24 weeks)
- Frequency of seizures(24 weeks)
- World Health Organization Quality of Life (WHO-QoL) scale(24 weeks)
- Patient-Reported Outcomes Measurement Information System (PROMIS) score(24 weeks)
研究者
Rodrigo Starosta
Assistant Professor
Oregon Health and Science University