Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)

Phase 3

Active, not recruiting

• Conditions: Autism Spectrum Disorder
• Interventions: Drug: Placebo; Drug: Lithium Carbonate

• Registration Number: NCT04623398
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

There is currently no treatment for the body symptoms of Autism Spectrum Disorders (ASD). However, basic research suggests that some forms of ASD may be alleviated, even in the adult stage. The genes involved in ASDs particularly impact synaptic homeostasis. Specific clinical trials in patients with synaptic mutations need to be carried out. In this spirit, ...

Detailed Description

Phase IIa intervention study, pilot, prospective, multicenter, randomized in 2 parallel arms, Li+ versus placebo, double-blind. The main objective of the study is to evaluate the effect of Li+ at 12 weeks, compared to placebo, on the social communication deficit in patients with Phelan-McDermid Syndrome (SHANK3 haploinsufficiency).
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Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-11-05
• Study First Submitted QC: 2020-11-09
• Study First Posted: 2020-11-10
• Study Start: 2022-02-21
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-24
• Last Update Posted: 2024-05-28
• Primary Completion: 2025-02
• Study Completion: 2025-02

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

• Children under 18 years of age
• Minimum weight of 20 kg for children aged 7 years old
• Patient with haplo deficiency SHANK3, i.e. carrier of a SHANK3 deletion (CNV) or a de novo truncating mutation in SHANK3 (Phelan McDermid syndrome);
• Total Social Responsiveness Scale - T score (SRS) of at least 66
• Patients of childbearing age who are sexually active must agree to use a highly effective form of contraception (estrogen-progestin or progestin-only contraception, or an intrauterine device, or contraceptive abstinence).
• Affiliation to a social security system
• Signature of the consent by the holders of parental authority
• Non-participation in another clinical trial
• Diagnosis of Autism Spectrum Disorders (DSM-5 criteria) confirmed by Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Scale (ADOS-II)
• IQ Assessment
• Beta-HCG negative

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Exclusion Criteria

• Hepatic or renal insufficiency (disturbed liver function tests, abnormal creatinine clearance);
• Unbalanced thyroid or diabetic pathology;
• Cardiac pathology: Brugada syndrome or family history of Brugada syndrome, heart failure;
• Addison's disease;
• Unstable epileptic disease.
• Patient with concomitant diseases judged for which the experimental treatment with Li + could compromise tolerance ;
• History of allergy to Li+;
• Allergy to lactose, lactose being the sole diluent and excipient of the prepared form.
• Initiation of co-occurring cognitive-behavioural therapy that is specifically focused on autistic symptoms within 6 weeks prior to inclusion;
• Any introduction of psychotropic drugs within 2 weeks prior to trial, including neuroleptics, monoamine oxidase inhibitors, stimulants, antidepressants. For neuroleptic drugs and Fluoxetine, this delay should be 4 weeks prior to the trial;
• Serious behavioural problems or refusal to take medication that does not allow for compliance;
• Inability to perform blood tests to check lithemia when the patient is included.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Capsules containing lactose monohydrate in all points resembling the capsules of active ingredients. Capsules of pla62.5 mg, pla125 mg and pla250 mg (pla=placebo)
Lithium	Lithium Carbonate	Li+ is an FDA (NDA: 016834) and ANSM (AMM 3400931376339) approved drug. There are two lithium salts that are marketed in France, Teralithe LI (cp 250mg) and Teralithe LP (cp 400mg). The experimental drugs in this study will be lithium carbonate capsules dosed at 62.5mg, 125mg and 250mg prepared as hospital preparations for clinical trials.

Primary Outcome Measures

Name	Time	Method
Score social responsiveness scale	12 weeks	Severity of Autistic Symptoms - Social Responsiveness Scale - Total score at 12 weeks.

Secondary Outcome Measures

Name	Time	Method
Score social responsiveness scale	Baseline (At randomization) , 4 weeks, 8 weeks, and 16 to 18 weeks after stopping the treatment	Severity of Autistic Symptoms - Social Responsiveness Scale. Evaluate the effect of the treatment on the severity of autistic symptoms.; Exploring the improvement of cardinal autistic symptoms (particularly social communication) during the therapeutic trial.
score of child's sleep disorder rating scale	Baseline (At randomization) , 4 weeks, 8 weeks, 12 weeks and 16 to 18 weeks after stopping the treatment	Evaluate the effect of the treatment on Child's Sleep Disorder
Score of Dunn Sensory Profile	4 weeks, 8 weeks, 12 weeks and 16 to 18 weeks after stopping the treatment	Evaluate the effect of the treatment on the improvement of cardinal autistic symptoms (particularly social communication) during the therapeutic trial.
score of autism diagnosis observation scale	Baseline (At randomization) and 12 weeks	Autism Diagnosis Observation Calibrated Severity Score. Evaluate the effect of the treatment on the improvement of cardinal autistic symptoms (particularly social communication) during the therapeutic trial.
Score of attention deficit hyperactivity disorder	Baseline (At randomization) 4 weeks, 8 weeks, 12 weeks, and 16 to 18 weeks after stopping the treatment	assessment of hyperactivity. Evaluate the effect of the treatment on the improvement of cardinal autistic symptoms (particularly social communication) during the therapeutic trial.
Score of Aberrant Behavior checklist scale	Baseline (At randomization), 4 weeks, 8 weeks and 12 weeks	Aberrant Behavior Checklist Scale - Social Withdrawal Subscale. Exploring aberrant, stereotyped, repetitive and obsessive behaviours (sub-scores and total score) and co-morbidities
score of global functioning	Baseline (At randomization), 4 weeks, 8 weeks, 12 weeks and 16 to 18 weeks after stopping the treatment	Clinical Global Improvement - Improvement and Severity Scores. Evaluate the effect of the treatment on the global functioning of patients and the impact on their environment
Score of surrounding constraints	Baseline (At randomization), 4 weeks, 8 weeks, 12 weeks and 16 to 18 weeks after stopping the treatment	Surrounding Constraints - Caregiver Strain Index. Evaluate the effect of the treatment on the global functioning of patients and the impact on their environment
Score of Vineland Adaptive Behavior Composite	Baseline (At randomization) and12 weeks	Evaluate the effect of the treatment on the global functioning of patients and the impact on their environment
score of Columbia Suicide Severity Rating Scale	Baseline (At randomization)and 12 weeks	Monitoring suicide risk and suicidal risk via the Columbia Suicide Severity Rating Scale (C-SSRS)

Trial Locations

Locations (1)

Hôpital Robert Debré; 🇫🇷 Paris, France