Study of L-dopa Treatment in Patients With a Neurodevelopmental Disorder (CTNNB1 Gene)

NCT07614126 | Recruiting

• 1 other identifier: RECMPL23_0426
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Neurodevelopmental disorders (NDD) encompass conditions that impair cognitive and/or emotional development in children, significantly impacting school, social, and family life. They are often linked to genetic causes and, in most cases, lack curative treatment. Among these disorders, monoallelic variations in the CTNNB1 gene cause a rare syndrome known as NEDSDV (Neurodevelopmental disorder with spastic diplegia and visual defects, OMIM: 615075). About twenty patients are reported in France. This syndrome is characterized by global developmental delay, intellectual disability, axial hypotonia, autistic traits, microcephaly, and sometimes ocular anomalies. The clinical profile resembles that of cerebral palsy, and CTNNB1 syndrome is considered a genetic form of this condition, accounting for roughly 4% of cases where a gene has been identified. Motor impairment is a core feature, with a wide range of movement disorders. Research remains limited, except for a recent publication. Dystonic hypertonia of the lower limbs is frequently described, more pronounced distally than proximally, without pyramidal signs. Spasticity is less common. Gait has been poorly studied: it may be absent or, when acquired, unstable, often tiptoe, and sometimes broad-based, resembling ataxia despite the absence of cerebellar signs. These motor features are difficult to detect before one year of age. To date, no longitudinal studies exist on motor or cognitive progression in CTNNB1 patients; available data are cross-sectional and do not suggest cognitive decline. From a pathophysiological perspective, the CTNNB1 gene encodes β-catenin, a key protein in cell adhesion and Wnt signaling, involved in cell differentiation and tissue homeostasis. It plays an essential role in embryonic brain development, particularly neuritogenesis and synaptic organization, with a specific impact on dopaminergic structures in the midbrain. Knock-out animal models show severe reduction in dopaminergic neurogenesis. These findings suggest that CTNNB1 anomalies lead to secondary dopaminergic deficits, contributing to clinical signs. The hypothesis is that this deficit could be partially corrected by dopamine supplementation. Regarding treatment, L-dopa (levodopa), used in dopaminergic disorders, has shown beneficial effects in a CTNNB1 patient. In our neuropediatrics department, two patients treated with L-dopa exhibited notable improvements in alertness, language, and motor skills within two months. These observations support the hypothesis that L-dopa may improve certain motor and non-motor symptoms in these patients. In summary, CTNNB1 syndrome is a rare form of NDD, clinically similar to cerebral palsy, with complex motor disorders and a probable dopaminergic deficit. Current evidence calls for further research, including longitudinal studies and therapeutic trials targeting the dopaminergic pathway.

Conditions

CTNNB1; L-DOPA

Outcome Measures

Primary Outcomes (1)

• Assessment of motor skills

  Change in overall motor score using the GMFM-88 scale before treatment (D1) and at 6 months.

  Baseline and 6 month follow-up visit

Secondary Outcomes (10)

• Assessment of motor skills

  6 month follow-up visit and end-of-study visit at 12 months

• Assessment of motor skills

  Baseline, 6 month follow-up visit and end-of-study visit at 12 months

• Cognitive assessment

  Baseline and end-of-study visit at 12 months

• Cognitive assessment

  Baseline and end-of-study visit at 12 months

• Cognitve assessment

  Baseline and end-of-study visit at 12 months

Study Arms (1)

Participant

EXPERIMENTAL

Treatment with L-dopa combined with a peripheral decarboxylase inhibitor (carbidopa) will be introduced gradually over a period of one year from the start of treatment. Motor, cognitive, quality of life and tolerance assessments will be carried out before treatment and at 6 and 12 months.

Drug: L-Dopa

Interventions

L-Dopa DRUG

Treatment with L-dopa combined with a peripheral decarboxylase inhibitor (carbidopa) will be introduced gradually over a period of one year from the start of treatment. Motor, cognitive, quality of life and tolerance assessments will be carried out before treatment and at 6 and 12 months.

Participant

Eligibility Criteria

• Age: 1 Year - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Aged between 1 and 15 years inclusive,
• Carrier of a pathogenic variant of CTNNB1,
• Patient with dystonia,
• Patient willing to comply with the contraception requirements detailed in the protocol.

You may not qualify if:

• Contraindication to treatment with L-dopa and carbidopa or any of its excipients,
• Current treatment with L-dopa, dopamine agonist, or dopamine blocker,
• Patients with peptic ulcer disease,
• Patients with open-angle glaucoma,
• Patients with orthostatic hypotension,
• Failure to obtain informed consent signed by both parents or legal guardians and the child's assent, if possible,
• Patients not affiliated with or not covered by a social security scheme,

Sponsors & Collaborators

• University Hospital, Montpellier: lead
• PTC Therapeutics: collaborator

Study Sites (1)

CHU de Montpellier

Montpellier, Hérault, 34295, France

RECRUITING

Related Publications (18)

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MeSH Terms

Interventions

Levodopa

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Central Study Contacts

Agathe Roubertie, Pr.

CONTACT

+33 4.67.33.01.82; a-roubertie@chu-montpellier.fr

Bérénice Lecardonnel

CONTACT

+33 4.67.33.73.71; b.lecardonnel@chu-montpellier.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2025
• First Posted: May 29, 2026
• Study Start: April 8, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: May 29, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)