Vanishing White Matter (VWM) Childhood ataxia with central nervous system hypomyelination (CACH)
Conditions
Interventions
Guanabenz
[(2,6-dichlorobenzylidene)amino] guanidine monoacetate
Sponsors
Amsterdam University Medical Centers, location VUmc, De Boelelaan 1117, 1081HV Amsterdam
Eligibility
Inclusion criteria
Inclusion criteria: 1. Each patient’s parents/legal guardians must sign an informed consent form (ICF) indicating that they understand the purpose of and procedures required for this study, are willing for their child to participate in the study and attend all scheduled assessments (on site or by video consultation as indicated per protocol), and are willing and able to comply with all study-related procedures, including maintaining contact with the site for at least 1 year, and adhere to the prohibitions and restrictions as specified in the protocol. Note: For each patient, both parents/legal guardians must give written consent. 2. Male or female who has a maximum disease duration of 8 years. 3. Genetically proven VWM with 2 clinically relevant mutations in one of the EIF2B1-5 genes and a brain MRI compatible with the diagnosis. 4. Disease onset before the age of 6 years. 5. Able to stand up and walk at least 10 steps with or without light support of one hand. 6. Lives within reasonable travel distance from Amsterdam.
Exclusion criteria
Exclusion criteria: 1. Clinically asymptomatic. 2. Comorbidity with another genetic defect. 3. Presence of an unrelated serious condition (eg, developmental anomaly, cardiac, liver or kidney disease). 4. Participation in another clinical study with therapeutic intervention. 5. Unable or unwilling to come to the study site as required by the protocol. 6. Unable to undergo MRI due to metal-containing implants, such as cochlea implant, neurostimulator or pacemaker. 7. Family situation in which adherence to the study medication or follow-up procedures cannot be guaranteed. 8. Known allergy or hypersensitivity to guanabenz or to any of the other components of the formulation used in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| •All adverse events and serious adverse events collected from the start of study treatment until the end of the study, applying the most recent version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, version 5.0, 27-Nov-2017), as well as applying: -Scales to specifically monitor the 2 most important adverse events in children (daytime drowsiness and headache): the PDSS and the Faces Pain Scale to grade headache. -A scale to grade the impact of adverse events on daily life. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Guanabenz PK parameters in plasma, such as maximum plasma concentration (Cmax), area under the plasma concentration-time curve (AUC), half-life, and predicted trough concentration (Ctrough) at steady state • Quantitative brain MRI parameters: Diffusion Tensor Imaging (DTI), Chemical Shift Imaging (CSI), Neurite Orientation Dispersion and Density Imaging (NODDI), Myelin Water Fraction Imaging (MWFI) • Clinical parameters: Health Utility Index (HUI), Euro-Quality of Life Instrument 5D, 5 levels (EQ-5D-5L), Euro-Quality of Life Instrument 5D, 5 levels (EQ-5D-Y), Vineland Adaptive Behavior Scales, 3rd edition (Vineland-3), Gross Motor Function Measure (GMFM), Leiter International Performance Scale (LIPS), Gross Motor Function Classification for Metachromatic Leukodystrophy (GMFC-MLD), Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), Expressive Language Function Classification for Metachromatic Leukodystrophy (ELFC-MLD), Communication Function Classification System (CFCS) and Eating and Drinking Ability Classification System (EDACS) • Overall survival | — |
Contacts
Public ContactMarjo S. van der Knaap
Amsterdam University Medical Centers, location VU University Medical Center
Outcome results
None listed