L-fucose supplementation for adults with GLUT1 deficiency

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

This trial will test whether taking L-fucose supplements helps reduce ataxia and other symptoms in adults with GLUT1 deficiency.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Oregon Health and Science University (Academic / other)
• Locations: 1 site (Portland, Oregon)
• Trial ID: NCT07432490 on ClinicalTrials.gov

What this trial studies

This single-center, randomized, double-blind, placebo-controlled cross-over Phase II trial at Oregon Health & Science University tests oral L-fucose versus placebo in adults with confirmed GLUT1 deficiency and ataxia. Eligible participants are 18 years or older with molecular, CSF, or clinical confirmation of GLUT1DS and will receive both study drug and placebo in separate blinded treatment periods. The protocol requires stable neurological medications for at least 90 days and excludes recent use of fucose- or mannose-containing supplements, with safety and exploratory motor and neurological outcomes collected during each period. The cross-over design lets each participant serve as their own control to detect within-person changes in symptoms.

Who should consider this trial

Good fit: Adults (≥18) with confirmed GLUT1DS by genetic testing, low CSF glucose, or consistent clinical features who have ataxia, can swallow liquids, have stable neurological medications for ≥90 days, and have not used fucose- or mannose-containing supplements in the past year are ideal candidates.

Not a fit: Patients under 18, those without ataxia, people with significant liver, kidney, hematologic, or metabolic disorders, those unable to swallow liquids, or those with recent neurological medication changes or recent fucose/mannose supplement use may not receive benefit or are excluded.

Why it matters

Potential benefit: If successful, L-fucose could improve motor control and reduce ataxia in adults with GLUT1 deficiency, potentially improving daily function.

How similar studies have performed: This approach is largely novel for GLUT1DS with limited human data; there are some preclinical studies and anecdotal reports but no large controlled trials showing clear benefit to date.

Eligibility criteria

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

Where this trial is running

Portland, Oregon

• Oregon Health and Science University — Portland, Oregon, United States (Recruiting)

Study contacts

• Study coordinator: Celena Byerlee-Dixon

Conditions Glut1 Deficiency; GLUT1DS1; GLUT1 Deficiency; GLUT1 Deficiency Syndrome; GLUT1DS; SLC2A1; Fucose; L-fucose