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

NCT04623398 | Completed Phase 3

• 1 other identifier: P160914J
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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, patients with deleterious mutations in SHANK3 represent a paradigm. The induced pluripotent stem cells (iPSc) carrying SHANK3 mutations and derived in neurons, can be used for high-throughput screening of pharmacological substances and allow the identification of compounds that can restore the expression level of SHANK3. The objective of this proposed project is to test one of the compounds identified by research on these iPSc as a novel treatment for social communication deficit in patients with deleterious mutations in SHANK3. Its effect on the symptoms of the social deficit could represent a new perspective for other forms of idiopathic autism.

Conditions

Autism Spectrum Disorder

Keywords

autism; Lithium

Outcome Measures

Primary Outcomes (1)

• Score social responsiveness scale

  Severity of Autistic Symptoms - Social Responsiveness Scale - Total score at 12 weeks.

  12 weeks

Secondary Outcomes (10)

• Score social responsiveness scale

  Baseline (At randomization) , 4 weeks, 8 weeks, and 16 to 18 weeks after stopping the treatment

• score of autism diagnosis observation scale

  Baseline (At randomization) and 12 weeks

• Score of attention deficit hyperactivity disorder

  Baseline (At randomization) 4 weeks, 8 weeks, 12 weeks, and 16 to 18 weeks after stopping the treatment

• 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

• Score of Dunn Sensory Profile

  4 weeks, 8 weeks, 12 weeks and 16 to 18 weeks after stopping the treatment

Study Arms (2)

Lithium

EXPERIMENTAL

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.

Drug: Lithium Carbonate

Placebo

PLACEBO COMPARATOR

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)

Drug: Placebo

Interventions

Lithium Carbonate DRUG

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.

Lithium

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 7 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Robert Debré

Paris, 75019, France

Location

MeSH Terms

Conditions

Autism Spectrum Disorder; Autistic Disorder

Interventions

Lithium Carbonate

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds

Study Officials

• Delorme Richard, PHD

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2020
• First Posted: November 10, 2020
• Study Start: February 21, 2022
• Primary Completion: August 26, 2024
• Study Completion: August 26, 2024
• Last Updated: October 2, 2025

Record last verified: 2025-09

Locations

FR (1)