Child, Neurodevelopmental Delay, Williams Syndrome
Conditions
Keywords
clemastine fumarate, Williams syndrome, MRI
Brief summary
This study focuses on therapeutic targets for cognitive, motor, and social impairments in Williams syndrome by reversing brain myelin defects caused by GTF2I. The primary objective of the study was to test and evaluate the initial efficacy and safety of Clomastine fumarate in the treatment of Williams syndrome.
Detailed description
The primary objective of this study was to evaluate the initial efficacy and safety of Clomastine fumarate in the treatment of Williams syndrome. The secondary objective is to study Clomastine fumarate in relation to mechanisms of action, safety, and/or pathological mechanisms. This study was a randomized, cross-over, placebo-controlled design. Each participant will be randomly assigned to two groups through baseline assessment (see study results), with Group A receiving the FDA-approved drug Clemastine at a weight-dependent dose (see dosing table below) for the first cycle and placebo for the second cycle. Group B will be treated with placebo for the first cycle and the FDA-approved drug Clemastine for the second cycle.
Interventions
DRUGClemastine Fumarate Tablets
clemastine fumarate (0.178 mg/kg/day), three months
DIETARY_SUPPLEMENTcorn starch tablets
The dose was administered 2mg once daily in a double-blind random crossover method
Sponsors
Qilu Hospital of Shandong University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
3 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
1. Age 3-12 years old; 2. Positive fluorescence in situ hybridization (FISH) test confirmed Williams syndrome; 3. GTF2I gene mutation was detected by whole exon; 4. Heart safety variables are normal (e.g. normal ECG, blood pressure 120-129/80-84)
Exclusion criteria
1. WS patients with other gene mutations; 2. Used antihistamines, monoamine oxidase inhibitors, barbiturates and sedatives, as well as drugs affecting cognitive behavior, limb movement, white matter myelin, and MRI within 2 months before enrollment; 3. Patients with narrow-angle glaucoma, narrow peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic hypertrophy and bladder neck obstruction; Accompanied by severe immunodeficiency disease; 4. Allergic to Clomastine fumarate or other arylalkylamine antihistamines or any receptor; 5. According to the recent interpretation of MRI and neuroradiology experts or WS, there are obvious brain lesions that are not related to WS disease; 6. Clinically significant metabolic, hematological, liver, immune, urinary, endocrine, neurological, pulmonary, psychiatric, skin, allergic, renal, or other major diseases that may affect the interpretation of study findings or patient safety in WS's judgment;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anisotropy Score (FA) | baseline follow-up；D90; D194 | Measuring by Magnetic resonance diffusion tensor imaging (DTI) |
| Radial diffusion rate (RD) | baseline follow-up；second month；fourth month | Measuring by Magnetic resonance diffusion tensor imaging (DTI) |
| axial diffusivity (AD) | baseline follow-up；D90；D194 | Measuring by Magnetic resonance diffusion tensor imaging (DTI) |
| mean diffusivity (MD) | baseline follow-up；D90; D194 | Measuring by Magnetic resonance diffusion tensor imaging (DTI) |
| Peabody（Motion Estimation Timewarp）score | baseline follow-up；second month；fourth month | Assessing motion skills |
| Gesell Development Scale | baseline follow-up；second month；fourth month | Assessing neurodevelopment |
| quotients (IQs) of the WISC-IV | baseline; D90 ; D194 | quantify intelligence quotients (IQs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Differential pressure across valves | baseline follow-up；second month；fourth month | Measuring by Cardiac color ultrasound |
| Thyroid hormone value | baseline follow-up；second month；fourth month | — |
| Conners Parent Symptoms Questionnaire Score | baseline follow-up；second month；fourth month | Assessing adaptability |
| Vailand-3 scale | baseline follow-up；second month；fourth month | Assessing neurodevelopment |
| CSHQ Children's Sleep Habits Questionnaire Score | baseline follow-up；second month；fourth month | Assessing sleeping |
| SRS Score 2(Social Response Scale2) score | baseline follow-up；D90; D194 | Assessing social skills |
| Score of the Chinese Communicative Development Inventories | baseline; D90; D194 | — |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORcao aihua, post-doctoral
Qilu Hospital of Shandong University
Outcome results
None listed