Clemastine Fumarate in the Treatment of Neurodevelopmental Delays in Williams Syndrome

NCT06315699 | Completed Phase 2 FDA Drug

• 2 other identifiers: QL000001MR-37-24-002019
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Williams Syndrome; Child; Neurodevelopmental Delay

Keywords

clemastine fumarate; Williams syndrome; MRI

Outcome Measures

Primary Outcomes (7)

• Anisotropy Score (FA)

  Measuring by Magnetic resonance diffusion tensor imaging (DTI)

  baseline follow-up；D90; D194

• Radial diffusion rate (RD)

  Measuring by Magnetic resonance diffusion tensor imaging (DTI)

  baseline follow-up；second month；fourth month

• 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

• 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

• quotients (IQs) of the WISC-IV

  quantify intelligence quotients (IQs)

  baseline; D90 ; D194

Secondary Outcomes (7)

• Differential pressure across valves

  baseline follow-up；second month；fourth month

• Thyroid hormone value

  baseline follow-up；second month；fourth month

• Conners Parent Symptoms Questionnaire Score

  baseline follow-up；second month；fourth month

• Vailand-3 scale

  baseline follow-up；second month；fourth month

• CSHQ Children's Sleep Habits Questionnaire Score

  baseline follow-up；second month；fourth month

Study Arms (2)

Clemastine

EXPERIMENTAL

Phase1: Clemastine，tablet，0.178 mg/kg/day，three months; Phase2 placebo (corn starch tablets) three months

Drug: Clemastine Fumarate Tablets

corn starch tablets

PLACEBO COMPARATOR

Phase1: placebo (corn starch tablets) three months; Phase2: Clemastine，tablet，0.178 mg/kg/day，three months

Dietary Supplement: corn starch tablets

Interventions

Clemastine Fumarate Tablets DRUG

clemastine fumarate (0.178 mg/kg/day), three months

Clemastine

corn starch tablets DIETARY_SUPPLEMENT

The dose was administered 2mg once daily in a double-blind random crossover method

corn starch tablets

Eligibility Criteria

• Age: 3 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 3-12 years old;
• Positive fluorescence in situ hybridization (FISH) test confirmed Williams syndrome;
• GTF2I gene mutation was detected by whole exon;
• Heart safety variables are normal (e.g. normal ECG, blood pressure 120-129/80-84)

You may not qualify if:

• WS patients with other gene mutations;
• 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;
• Patients with narrow-angle glaucoma, narrow peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic hypertrophy and bladder neck obstruction; Accompanied by severe immunodeficiency disease;
• Allergic to Clomastine fumarate or other arylalkylamine antihistamines or any receptor;
• According to the recent interpretation of MRI and neuroradiology experts or WS, there are obvious brain lesions that are not related to WS disease;
• 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;

Sponsors & Collaborators

• Qilu Hospital of Shandong University: lead

Study Sites (1)

Qilu Hospital of Shandong University

Tainan, Shangdong, 250012, China

Location

MeSH Terms

Conditions

Williams Syndrome

Interventions

Clemastine; Starch

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Aortic Stenosis, Supravalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Polysaccharides

Study Officials

• cao aihua, post-doctoral

  Qilu Hospital of Shandong University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2024
• First Posted: March 18, 2024
• Study Start: March 20, 2024
• Primary Completion: March 2, 2025
• Study Completion: December 30, 2025
• Last Updated: March 19, 2026

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)