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.

Study Overview

• Status: Completed
• Conditions: Child; Williams Syndrome; Neurodevelopmental Delay
• Intervention / Treatment: Drug: Clemastine Fumarate Tablets; Dietary supplement: corn starch tablets

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shangdong
    • Tainan, Shangdong, China, 250012
      • Qilu Hospital of Shandong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clemastine; Phase1: Clemastine，tablet，0.178 mg/kg/day，three months; Phase2 placebo (corn starch tablets) three months	Drug: Clemastine Fumarate Tablets; clemastine fumarate (0.178 mg/kg/day), three months
Placebo Comparator: corn starch tablets; Phase1: placebo (corn starch tablets) three months; Phase2: Clemastine，tablet，0.178 mg/kg/day，three months	Dietary supplement: corn starch tablets; The dose was administered 2mg once daily in a double-blind random crossover method

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radial diffusion rate (RD)	Measuring by Magnetic resonance diffusion tensor imaging (DTI)	baseline follow-up；second month；fourth month
Peabody（Motion Estimation Timewarp）score	Assessing motion skills	baseline follow-up；second month；fourth month
Gesell Development Scale	Assessing neurodevelopment	baseline follow-up；second month；fourth month
Anisotropy Score (FA)	Measuring by Magnetic resonance diffusion tensor imaging (DTI)	baseline follow-up；D90; D194
axial diffusivity (AD)	Measuring by Magnetic resonance diffusion tensor imaging (DTI)	baseline follow-up；D90；D194
mean diffusivity (MD)	Measuring by Magnetic resonance diffusion tensor imaging (DTI)	baseline follow-up；D90; D194
quotients (IQs) of the WISC-IV	quantify intelligence quotients (IQs)	baseline; D90 ; D194

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differential pressure across valves	Measuring by Cardiac color ultrasound	baseline follow-up；second month；fourth month
Thyroid hormone value		baseline follow-up；second month；fourth month
Conners Parent Symptoms Questionnaire Score	Assessing adaptability	baseline follow-up；second month；fourth month
Vailand-3 scale	Assessing neurodevelopment	baseline follow-up；second month；fourth month
CSHQ Children's Sleep Habits Questionnaire Score	Assessing sleeping	baseline follow-up；second month；fourth month
SRS Score 2(Social Response Scale2) score	Assessing social skills	baseline follow-up；D90; D194
Score of the Chinese Communicative Development Inventories		baseline; D90; D194

Collaborators and Investigators

• Sponsor: Qilu Hospital of Shandong University
• Investigators: Principal Investigator: cao aihua, post-doctoral, Qilu Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2024
• Primary Completion (Actual): March 2, 2025
• Study Completion (Actual): December 30, 2025

Study Registration Dates

• First Submitted: March 4, 2024
• First Submitted That Met QC Criteria: March 11, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: MRI; Williams syndrome; clemastine fumarate
• Additional Relevant MeSH Terms: Aortic Valve Disease; Neurologic Manifestations; Nervous System Diseases; Cardiovascular Diseases; Heart Diseases; Genetic Diseases, Inborn; Neurobehavioral Manifestations; Heart Valve Diseases; Congenital Abnormalities; Intellectual Disability; Aortic Valve Stenosis; Chromosome Disorders; Aortic Stenosis, Supravalvular; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Williams Syndrome; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dietary Carbohydrates; Carbohydrates; Polymers; Macromolecular Substances; Polysaccharides; Pyrrolidines; Glucans; Biopolymers; Clemastine; Starch
• Other Study ID Numbers: QL000001; MR-37-24-002019 (Registry Identifier: Chinese Clinical Trial Registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes