Cornelia De Lange Syndrome: Assessing Positive Effects of Lithium Treatment
ConditionCornelia De Lange Syndrome
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age4+
SponsorUniversity of Milan
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Single group
Treatments tested in this trial
Lithium Carbonate Capsule
Drug10mg/Kg twice a day, 150mg or 300mg Lithium Carbonate
Treatment groups
34 Participants
are divided into 1 treatment groupGroup A: CdLS patients with NIPBL mutationExperimental treatment 1 intervention
Trial outcomes
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
Time frame
Change at 12 months from baseline of supplementationSecondary outcomes
1
Communication
Social Communication Questionnaire questionnaire (SCQ; Rutter, Bailey\&Lord, 20032) to assess communication skills and social functioning; minimum score: 0; maximum score:40. Higher score means worse outcome.
Time frame
Change at 12 months from baseline of supplementation2
Behaviour
Childhood Autism Rating Scale (CARS 2 -T3) to assess autistic behaviors. minimum score: 15; maximum score:60. Higher score means worse outcome. Furthermore, for very serious patients, for whom a direct assessment with the Leiter could be insignificant or impossible, it would allow for the adaptation quotient (QD).
Time frame
Change at 12 months from baseline of supplementation3
Sleep disturbances
Sleep quality through the Sleep disturbances scale for children (SDSC5), to be administered to parents; there are two versions, one for subjects between 6-16 years, the other for children 3-6 years. minimum total score: 26; maximum total score:130. Higher scores mean worse outcome.
Time frame
Change at 12 months from baseline of supplementation4
Clinical features
Impression of change Clinical Global Impression of Change (CGI-C) filled out by the clinician at each visit. minimum total score:0; maximum total score:30. Higher scores mean worse outcome.
Time frame
Change at 12 months from baseline of supplementationSponsors and contacts
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Source ClinicalTrials.gov