Lithium treatment for TBR1-related neurocognitive disorder
A Pilot, Multicentre, Controlled, Open-label Study Evaluating 24 Months of Lithium Carbonate Treatment in Patients With TBR1-related Neurocognitive Disorder
This pilot will try lithium carbonate in people aged 6 and older who have a pathogenic TBR1 variant to see if it improves cognitive and behavioral symptoms.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 12 (estimated) |
| Ages | 6 Years and up |
| Sex | All |
| Sponsor | Centre Hospitalier Universitaire Dijon Academic / other |
| Locations | 1 site (Dijon) |
| Trial ID | NCT06776848 on ClinicalTrials.gov |
What this trial studies
TBR1 is a brain-specific gene implicated in autism spectrum disorders and intellectual disability, and animal and cell studies suggest that some pathogenic variants disrupt normal brain function. This pilot, multicentre, controlled open-label study gives 24 months of lithium carbonate with an initial observation phase and ongoing biological monitoring. Eligible participants are people aged 6 or older with a confirmed pathogenic or likely pathogenic TBR1 variant who can take oral tablets and meet contraception and caregiver attendance requirements. The trial will track cognitive and behavioral outcomes alongside safety and laboratory measures to determine whether lithium produces measurable benefit.
Who should consider this trial
Good fit: Ideal candidates are individuals aged 6 years or older with a confirmed pathogenic or likely pathogenic TBR1 variant who can swallow tablets, have a caregiver able to attend visits, and use stable psychoactive medications if applicable.
Not a fit: Patients without a confirmed TBR1 pathogenic variant, those unable to take oral lithium, pregnant people, or those with medical contraindications to lithium are unlikely to benefit from this trial.
Why it matters
Potential benefit: If successful, lithium could improve social interaction, cognitive flexibility, or memory in people with TBR1-related neurocognitive disorder and offer a targeted treatment option.
How similar studies have performed: This is a novel application for TBR1-related disorder, though preclinical mouse studies and lithium's use in other neuropsychiatric conditions provide some supporting evidence.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Dijon
- CHU Dijon Bourgogne — Dijon, France (Recruiting)
Study contacts
- Study coordinator: Sophie NAMBOT
- Email: sophie.nambot@chu-dijon.fr
- Phone: 0380295313
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.