Clemastine Fumarate in the Treatment of Neurodevelopmental Delays in Williams Syndrome

Randomized, Double-blind, Controlled Study of Clomastine Fumarate in the Treatment of Williams Syndrome

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.

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.

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;