Clemastine Treatment in Individuals With Williams Syndrome

Clemastine Treatment in Individuals With Williams Syndrome- a Double-blind Placebo Control to Assess the Safety and Efficacy

This study explores the neurobiological etiology of Williams syndrome and potential therapeutic targets for associated social, motor, and cognitive abnormalities. The main translational objective will be to test the effectiveness of Clemasntine on neurocognitive and other associated abnormalities in individuals with Williams syndrome.

Study Overview

• Status: Active, not recruiting
• Conditions: Williams Syndrome
• Intervention / Treatment: Drug: Open Label Clemastine with a blinded randomize withdrawal

Detailed Description

The overarching aim of the research proposed is to examine the safty of Clemastine use for individuals with Williams syndrome. Further, we wish to examine the relationship between Clemastine treatment and cognitive, motor and behavioral deficits in individuals with Williams syndrome. This study is an open-label study with a blinded randomize withdrawal. Each participant will go through a baseline evaluation (see study outcomes) and will be treated with the FDA approved drug Clemastine, in an age dependent dose (dosage table below). After a substantial improvement will be noticed, the participants will be divided into 2 groups, in a randomized, double-blind, placebo-control study design.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Ramat Gan, Israel
    • Child and Adolescent Psychiatry Unit, Sheba Medical Center
  • Tel Aviv, Israel
    • Tel Aviv University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Individuals with Williams syndrome, which has been confirmed by genetic testing.
• Ages 6-30.
• Normal values in safety variables (e.g. Normal ECG 120-129/80-84).
• No change in psychotropic medications and dosage during the last 4 weeks.
• During the study, no pharmacological change that may impact the study (e.g. ADHD
• medications).

Exclusion Criteria:

• Individuals with another genetic disorder besides Williams syndrome.
• Individuals with Williams syndrome, younger than 6 or older than 30 years old.
• Significant change in normal values in safety variables (e.g. high or low ECG).
• Change in medications and dosage during the last 4 weeks prior the beginning and
• during the study.
• Pregnancy.
• Using addictive substances such as alcohol.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open Label	Drug: Open Label Clemastine with a blinded randomize withdrawal; Clemastine will be given in doses as the maximum dose recommended for allergy condition. Age 6-12 years 4.02 mg/day, age 12-30 years 8.04 mg/day.
Experimental: Blinded randomize withdrawal	Drug: Open Label Clemastine with a blinded randomize withdrawal; Clemastine will be given in doses as the maximum dose recommended for allergy condition. Age 6-12 years 4.02 mg/day, age 12-30 years 8.04 mg/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurocognitive measures	Wechsler Intelligence Scale: The standard age-appropriate Wechsler scale. Wechsler Intelligence Scale for Children, 4th edition(Wechsler 1991, Wechsler 2003) for subjects 17 years and younger and the Wechsler Adult Intelligence Scale, 3rd edition (WAIS III)(Wechsler 1997) for subjects older than 17 years. NIH ToolBox (NIHTB): the NIHTB is a computerized neurocognitive battery developed by NIH that was designed to include measures of cognitive flexibility and inhibitory control, as well as a measure of working memory. http://www.healthmeasures.net/explore-measurement-systems/nih-toolbox/	December 2024

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor and Neurological assessment. Motor and Neurological assessment. Motor and Neurological assessment. Motor and neurolocgial measures	The Beery-Buktenica Developmental Test of Visual-Motor Integration GAITRite walkway: GAITRite is a sensitive walkway measuring temporal and spatial parameters. Psychiatric evaluation: a semi-structured interview for neuropsychiatric diagnoses with the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. The Child Behavior Checklist: measures behavioral/emotional problems and competencies. Attention Deficit Hyperactivity Disorder Rating Scale. The Screen for Child Anxiety-Related Emotional Disorders. The Social Responsiveness Scale-Second Edition. Adaptive Behavior Assessment System-2nd Edition.	December 2024

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Collaborators: Tel Aviv University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: October 5, 2023
• First Submitted That Met QC Criteria: October 11, 2023
• First Posted (Actual): October 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cognition; Clemastine; Myelination abnormalities
• 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; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dermatologic Agents; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Clemastine
• Other Study ID Numbers: 9011-21-SMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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