Clemastine Fumarate in the Treatment of Neurodevelopmental Delays in Williams Syndrome

Child Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06315699
• Other study ID #: QL000001
• Secondary ID: MR-37-24-002019
• Status: Recruiting
• Phase: Phase 3
• Start date: March 20, 2024
• Est. completion date: December 30, 2025

Study information

• Verified date: March 2024
• Source: Qilu Hospital of Shandong University
• Contact: cao aihua, post-doctoral
• Phone: 18560086317
• Email: xinercah[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 an open-label study with 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 30, 2025
• Est. primary completion date: March 2, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 6 Years

Eligibility

Inclusion Criteria:

1. Age 3-6 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;

Related Conditions & MeSH terms

• Child
• Neurodevelopmental Delay
• Syndrome
• Williams Syndrome

Intervention

Drug:
• Clemastine Fumarate Tablets
The dose was administered 2mg once daily in a double-blind random crossover method

Dietary Supplement:
• fructose
The dose was administered 2mg once daily in a double-blind random crossover method

Locations

Country	Name	City	State
China	Qilu Hospital of Shandong University	Tainan	Shangdong

Sponsors (1)

Lead Sponsor	Collaborator
Qilu Hospital of Shandong University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anisotropy Score (FA)	Measuring by Magnetic resonance diffusion tensor imaging (DTI)	baseline follow-up;second month;fourth month
Primary	Radial diffusion rate (RD)	Measuring by Magnetic resonance diffusion tensor imaging (DTI)	baseline follow-up;second month;fourth month
Primary	Apparent dispersion coefficient(ADC)	Measuring by Magnetic resonance diffusion tensor imaging (DTI)	baseline follow-up;second month;fourth month
Primary	Magnetization transfer ratio(MTR)	Measuring by Magnetic resonance diffusion tensor imaging (DTI)	baseline follow-up;second month;fourth month
Primary	SRS Score 2(Social Response Scale2) score	Assessing social skills	baseline follow-up;second month;fourth month
Primary	Peabody(Motion Estimation Timewarp)score	Assessing motion skills	baseline follow-up;second month;fourth month
Primary	Gesell Development Scale	Assessing neurodevelopment	baseline follow-up;second month;fourth month
Secondary	Differential pressure across valves	Measuring by Cardiac color ultrasound	baseline follow-up;second month;fourth month
Secondary	Thyroid hormone value		baseline follow-up;second month;fourth month
Secondary	Conners Parent Symptoms Questionnaire Score	Assessing adaptability	baseline follow-up;second month;fourth month
Secondary	Vailand-3 scale	Assessing neurodevelopment	baseline follow-up;second month;fourth month
Secondary	CSHQ Children's Sleep Habits Questionnaire Score	Assessing sleeping	baseline follow-up;second month;fourth month