A Placebo-controlled Evaluation of Low Dose Lithium Carbonate in Patients with TBR1-related Neurocognitive Disorders

Launched by CENTRE HOSPITALIER UNIVERSITAIRE DIJON · Jan 10, 2025

Keywords

ClinConnect Summary

This clinical trial is investigating the effects of a medication called lithium carbonate in patients who have a specific genetic change related to TBR1, which is linked to neurocognitive disorders such as autism and intellectual disabilities. The researchers want to see if low doses of lithium can improve symptoms like social interaction and cognitive abilities in individuals with these TBR1-related conditions. Currently, there are no treatments specifically targeting this genetic issue, so this trial aims to explore a new option that could help enhance the quality of life for affected individuals.

To participate in the trial, individuals must be at least 6 years old and have a confirmed TBR1 genetic variant. They also need to be able to take medication by mouth and have a parent or guardian who can assist and attend visits. Participants will be observed for 6 to 12 months before starting lithium treatment. During the trial, researchers will monitor how well the medication works and check for any side effects. It’s important for potential participants to know that they cannot have certain health issues or be on specific medications that might interfere with the study. Overall, this trial represents a promising step toward finding effective treatments for those impacted by TBR1-related disorders.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Written informed consent from the patient, parent or legal representative
• • ≥6 years old at the time of consent
• • Proven pathogenic or probably pathogenic TBR1 variant (SNV confirmed by Sanger sequencing or CNV including only TBR1)
• • If applicable: Stable concomitant psychoactive medication regimen (dose and schedule) ≥2 months prior to lithium initiation
• • Affected individuals able to take tablet /capsules orally
• • Highly effective method of contraception in affected female individuals of childbearing age (Combined hormonal contraception, progestogen-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system) during treatment and for at least 3 months after the final dose of lithium
• • Highly effective method of contraception in affected men individuals of childbearing age (condom) during the treatment and for at least 5 days after the final dose of lithium
• • 1 available parent/guardian able to attend all visits having acceptable reading skills
• Exclusion Criteria:
• Criteria related to associated pathologies leading to particular risks:
• • Renal/liver insufficiency (disturbed liver function, abnormal creatinine clearance)
• • Unbalanced thyroid or diabetic pathology
• • Long QT/Brugada syndrome or familial antecedent of Brugada syndrome, cardiac insufficiency
• • Addison disease, dehydration, sodium restriction
• • Non-stabilized epileptic disease.
• Criteria related to contra-indication to treatment:
• • Patient with concomitant diseases for which the experimental treatment by lithium could alter the tolerance
• • Hypersensitivity to lactose, lithium or one of its excipients
• • Patient with a wheat allergy (other than celiac disease)
• • Pregnant or breastfeeding woman
• Criteria related to treatments/procedures:
• • Parent/guardian incapable of expressing consent
• • Person not affiliated to a national health insurance scheme
• • Person subject to a court order
• • Cognitivo-behavioural therapy focused on ASD in 6 weeks previous to inclusion
• • Other genetic pathogenic variant associated to neurocognitive disorders
• • Any introduction of psychotropic molecules within 2 months prior to the trial, including neuroleptics, monoamine oxidase inhibitors, stimulants, antidepressants.
• • Concomitant use of Angiotensin-Converting Enzyme (ACE) inhibitor, angiotensin II receptor antagonists, Nonsteroidal anti-inflammatory drugs, diuretics.
• • Current lithium treatment
• • Severe behavioural disorder or refusal to take drug treatment not allowing for compliance with medication;
• • Impossibility to perform blood tests to check the lithiaemia when the patient is included.
• • Participation in another therapeutic trial