Autism Spectrum DisorderPhase 3LisphemNCT04623398
Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
A Phase 3 study testing Lithium Carbonate in people with Autism Spectrum Disorder, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 7 to 18 years
- Conditions the study is for
- Autism Spectrum Disorder
- What is being tested?
- Lithium Carbonate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteFrance
- Study dates
- 21 Feb 2022to 26 Aug 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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 ;
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency): Pilot Study.
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.
Read the 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).
The Secondary Objectives are :
- To evaluate the effect of Li+ at 12 weeks on all cardinal and main symptoms in patients suffering from Phelan-McDemid Syndrome (PMS).
- Evaluate the tolerance of Li + for 12 weeks in children suffering from PMS.
- Demonstrate the feasibility of a phase III, randomized controlled trial.
- Evaluate the residual effect of treatment at 16 to 18 weeks after stopping treatment)
- Evaluate the parents' feelings at the end of the study regarding the child's behavior and the impact on their daily lives
The treatment of the study is lithium carbonate: Li+ carbonate capsules are prepared from the raw material for pharmaceutical use .
Inclusion will be ensured by the clinical genetics centers. Psychiatric evaluation will be carried out by the investigative child psychiatry service.
Patients will be followed up by 2 referring physicians:
- a child psychiatrist, blind of the treatment arm, who will carry out the evaluations of the judgement criteria;
- a physician from the clinical investigation center, the only one informed of the attribution arm, who will ensure the adaptation of the LI dosage; an adaptation of the dummy dosage will be proposed to the patients on placebo to maintain the blind in this group as well. A lithiaemia will be performed every 4 days (+/- 1 day) until the target lithiaemia of 0.4-0.6 meq/L is reached with progressive increment of the lithium dose administered. The target blood lithium level must be reached within 20 days
As the evaluation is based on hetero-evaluation (by the parents), a placebo treatment remains necessary in the control arm.
Pharmaceutical preparations will be carried out for this pilot study: unit blister packaging of the active ingredient and the placebo.
- Conditions
- Autism Spectrum Disorder
- Being tested
- Lithium Carbonate, Placebo
- Keywords
- autism, Lithium
- Medical subject headings
- Autism Spectrum Disorder, Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lithium CarbonateDrug
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.
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Score social responsiveness scale
Severity of Autistic Symptoms - Social Responsiveness Scale - Total score at 12 weeks.
Measured: 12 weeks
Secondary outcomes (10)
Score social responsiveness scale
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.
Measured: Baseline (At randomization) , 4 weeks, 8 weeks, and 16 to 18 weeks after stopping the treatment
score of autism diagnosis observation scale
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.
Measured: Baseline (At randomization) and 12 weeks
Score of attention deficit hyperactivity disorder
assessment of hyperactivity. Evaluate the effect of the treatment on the improvement of cardinal autistic symptoms (particularly social communication) during the therapeutic trial.
Measured: 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
Evaluate the effect of the treatment on Child's Sleep Disorder
Measured: Baseline (At randomization) , 4 weeks, 8 weeks, 12 weeks and 16 to 18 weeks after stopping the treatment
Score of Dunn Sensory Profile
Evaluate the effect of the treatment on the improvement of cardinal autistic symptoms (particularly social communication) during the therapeutic trial.
Measured: 4 weeks, 8 weeks, 12 weeks and 16 to 18 weeks after stopping the treatment
Score of Aberrant Behavior checklist scale
Aberrant Behavior Checklist Scale - Social Withdrawal Subscale. Exploring aberrant, stereotyped, repetitive and obsessive behaviours (sub-scores and total score) and co-morbidities
Measured: Baseline (At randomization), 4 weeks, 8 weeks and 12 weeks
score of global functioning
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
Measured: Baseline (At randomization), 4 weeks, 8 weeks, 12 weeks and 16 to 18 weeks after stopping the treatment
Score of Vineland Adaptive Behavior Composite
Evaluate the effect of the treatment on the global functioning of patients and the impact on their environment
Measured: Baseline (At randomization) and12 weeks
Score of surrounding constraints
Surrounding Constraints - Caregiver Strain Index. Evaluate the effect of the treatment on the global functioning of patients and the impact on their environment
Measured: Baseline (At randomization), 4 weeks, 8 weeks, 12 weeks and 16 to 18 weeks after stopping the treatment
score of Columbia Suicide Severity Rating Scale
Monitoring suicide risk and suicidal risk via the Columbia Suicide Severity Rating Scale (C-SSRS)
Measured: Baseline (At randomization)and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2020
- Study start21 Feb 2022
- Primary completion26 Aug 2024
- Study completion26 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Delorme Richard, PHD, Principal investigator, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04623398
- Sponsor's protocol ID
- P160914J
- Acronym
- Lisphem
- Status last verified
- Sep 2025
- First submitted
- 5 Nov 2020
- Last updated
- 2 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency): Pilot Study.
- ClinicalTrials.gov ID
- NCT04623398
- Acronym / sponsor ID
- Lisphem / P160914J
- Conditions
- Autism Spectrum Disorder
- Keywords
- autism, Lithium
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 21 Feb 2022 (actual)
- Primary completion
- 26 Aug 2024 (actual)
- Study completion
- 26 Aug 2024 (actual)
- First posted
- 10 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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).
The Secondary Objectives are :
- To evaluate the effect of Li+ at 12 weeks on all cardinal and main symptoms in patients suffering from Phelan-McDemid Syndrome (PMS).
- Evaluate the tolerance of Li + for 12 weeks in children suffering from PMS.
- Demonstrate the feasibility of a phase III, randomized controlled trial.
- Evaluate the residual effect of treatment at 16 to 18 weeks after stopping treatment)
- Evaluate the parents' feelings at the end of the study regarding the child's behavior and the impact on their daily lives
The treatment of the study is lithium carbonate: Li+ carbonate capsules are prepared from the raw material for pharmaceutical use .
Inclusion will be ensured by the clinical genetics centers. Psychiatric evaluation will be carried out by the investigative child psychiatry service.
Patients will be followed up by 2 referring physicians:
- a child psychiatrist, blind of the treatment arm, who will carry out the evaluations of the judgement criteria;
- a physician from the clinical investigation center, the only one informed of the attribution arm, who will ensure the adaptation of the LI dosage; an adaptation of the dummy dosage will be proposed to the patients on placebo to maintain the blind in this group as well. A lithiaemia will be performed every 4 days (+/- 1 day) until the target lithiaemia of 0.4-0.6 meq/L is reached with progressive increment of the lithium dose administered. The target blood lithium level must be reached within 20 days
As the evaluation is based on hetero-evaluation (by the parents), a placebo treatment remains necessary in the control arm.
Pharmaceutical preparations will be carried out for this pilot study: unit blister packaging of the active ingredient and the placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lithium | Experimental | Drug: Lithium CarbonateLi+ 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. |
| Placebo | Placebo comparator | Drug: PlaceboCapsules containing lactose monohydrate in all points resembling the capsules of active ingredients. Capsules of pla62.5 mg, pla125 mg and pla250 mg (pla=placebo) |
Who may qualify
- Ages
- 7 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- 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).
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lithium CarbonateThe 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 |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Score social responsiveness scale
Time frame: 12 weeks
Severity of Autistic Symptoms - Social Responsiveness Scale - Total score at 12 weeks.
10 secondary outcomes
Score social responsiveness scale
Time frame: Baseline (At randomization) , 4 weeks, 8 weeks, and 16 to 18 weeks after stopping the treatment
score of autism diagnosis observation scale
Time frame: Baseline (At randomization) and 12 weeks
Score of attention deficit hyperactivity disorder
Time frame: 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
Time frame: Baseline (At randomization) , 4 weeks, 8 weeks, 12 weeks and 16 to 18 weeks after stopping the treatment
Score of Dunn Sensory Profile
Time frame: 4 weeks, 8 weeks, 12 weeks and 16 to 18 weeks after stopping the treatment
Score of Aberrant Behavior checklist scale
Time frame: Baseline (At randomization), 4 weeks, 8 weeks and 12 weeks
score of global functioning
Time frame: Baseline (At randomization), 4 weeks, 8 weeks, 12 weeks and 16 to 18 weeks after stopping the treatment
Score of Vineland Adaptive Behavior Composite
Time frame: Baseline (At randomization) and12 weeks
Score of surrounding constraints
Time frame: Baseline (At randomization), 4 weeks, 8 weeks, 12 weeks and 16 to 18 weeks after stopping the treatment
score of Columbia Suicide Severity Rating Scale
Time frame: Baseline (At randomization)and 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Delorme Richard, PHD principal investigator
APHP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lithium Carbonate in people with Autism Spectrum Disorder, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Score social responsiveness scale (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2025.