Cornelia De Lange Syndrome: Assessing Positive Effects of Lithium Treatment

NCT06789783 | Recruiting Phase 2

• 2 other identifiers: 210-18042023patients association
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The study "Cornelia de Lange Syndrome: assessing positive effects of Lithium treatment - CLoSER" aims to evaluate the effectiveness on behavioral modifications of lithium carbonate therapy in patients with Cornelia de Lange syndrome (CdLS). CdLS is a rare genetic disease caused by autosomal mutations dominant or X-linked. The prevalence of CdLS is estimated to be between 1:10,000-30,000 newborns, but it is probably underestimated because the most cases mild ones may go undiagnosed. This syndrome is characterized by slow growth before and after birth with intellectual disability and short stature, from major malformations such as facial anomalies, neurological disorders, gastrointestinal and musculoskeletal malformations. To date, for these patients only targeted medical and surgical therapeutic interventions are recommended for improving the quality of life. No drug therapy is validated for the cognitive/behavioral disorders. It has been shown that lihium-dependent activation of the WNT pathway is able to recover the Abnormal phenotype in many CdLS models. Lithium is already widely used in psychiatry and has a long history of clinical efficacy. Recently some studies are evaluating the effect of lithium in patients with characteristics common to CdLS showing promising results . This trial intends to transfer the preliminary data obtained from in vitro and in vivo studies on patients with CdLS. Given the currently untreatable nature of the syndrome, this treatment could represent a possible therapeutic strategy aimed at improving the behavioral and intellectual disabilities typical of CdLS.

Conditions

Cornelia De Lange Syndrome

Keywords

Lithium treatment

Outcome Measures

Primary Outcomes (1)

• Behaviour

  Behaviour assessed through the Aberrant Behaviour checklist (ABC1 scale) which mesaure psychiatric symptomatology and behavioral disorders also in patients with intellectual disabilities. minimum total score: 0; maximum total score:174. Higher scores mean worse outcome

  Change at 12 months from baseline of supplementation

Secondary Outcomes (7)

• Communication

  Change at 12 months from baseline of supplementation

• Behaviour

  Change at 12 months from baseline of supplementation

• Sleep disturbances

  Change at 12 months from baseline of supplementation

• Clinical features

  Change at 12 months from baseline of supplementation

• Cognitive Performance

  Change at 12 months from baseline of supplementation

Study Arms (1)

CdLS patients with NIPBL mutation

EXPERIMENTAL

Patients will be given 10mg/Kg twice a day, 150mg or 300mg Lithium Carbonate

Drug: Lithium Carbonate Capsule

Interventions

Lithium Carbonate Capsule DRUG

10mg/Kg twice a day, 150mg or 300mg Lithium Carbonate

CdLS patients with NIPBL mutation

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 4 years
• Body weight within the normal range in the reference range for CdLS, based on age and height
• Diagnosis of CdLS based on consensus clinical criteria and a confirmed mutation in the NIPBL gene
• Stable drug regimen for 4 weeks prior to starting the study
• Written consent signed by parent/legal guardian/representative prior to the screening visit
• Ability to take the study drug provided in capsules or drops (for younger patients and those with swallowing difficulties) or combined with food/drinks
• Caregiver must be able to understand the instructions and participate knowingly in the study

You may not qualify if:

• The patient is participating in another clinical trial
• QT interval prolongation, thyroid dysfunction, renal insufficiency, hepatic insufficiency, leukopenia, or other currently clinically significant medical disorders (as determined by the investigator), other than those directly related to CdLS
• QTcF interval on ECG greater than 450 msec
• Severe diabetes mellitus or inherited metabolic disorder

Sponsors & Collaborators

• University of Milan: lead

Study Sites (1)

University of Milan

Milan, MI, Italy

RECRUITING

Related Publications (1)

• Grazioli P, Parodi C, Mariani M, Bottai D, Di Fede E, Zulueta A, Avagliano L, Cereda A, Tenconi R, Wierzba J, Adami R, Iascone M, Ajmone PF, Vaccari T, Gervasini C, Selicorni A, Massa V. Lithium as a possible therapeutic strategy for Cornelia de Lange syndrome. Cell Death Discov. 2021 Feb 17;7(1):34. doi: 10.1038/s41420-021-00414-2.

  PMID: 33597506 BACKGROUND

MeSH Terms

Conditions

De Lange Syndrome

Interventions

Lithium Carbonate

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds

Study Officials

• Aglaia Vignoli, Professor, MD

  University of Milan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aglaia Vignoli, Professor, MD

CONTACT

+390264443960; aglaia.vignoli@unimi.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 19, 2024
• First Posted: January 23, 2025
• Study Start: May 1, 2024
• Primary Completion: September 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 28, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)