- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04623398
Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency) (Lisphem)
Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency): Pilot Study.
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Delorme Richard, PHD
- Phone Number: 01 40 03 41 30
- Email: richard.delorme@aphp.fr
Study Contact Backup
- Name: Maruani Anna, PHD
- Email: anna.maruani@aphp.fr
Study Locations
-
-
-
Paris, France, 75019
- Recruiting
- Hôpital Robert Debré
-
Contact:
- Delorme Richard, PHD
- Phone Number: 01 40 03 41 30
- Email: richard.delorme@aphp.fr
-
Contact:
- Maruani anna
- Email: anna.maruani@aphp.fr
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Lithium
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. |
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 Comparator: 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) |
Placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Score social responsiveness scale
Time Frame: 12 weeks
|
Severity of Autistic Symptoms - Social Responsiveness Scale - Total score at 12 weeks.
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Score social responsiveness scale
Time Frame: 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. |
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
|
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.
|
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
|
assessment of hyperactivity.
Evaluate the effect of the treatment on the improvement of cardinal autistic symptoms (particularly social communication) during the therapeutic trial.
|
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
|
Evaluate the effect of the treatment on Child's Sleep Disorder
|
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
|
Evaluate the effect of the treatment on the improvement of cardinal autistic symptoms (particularly social communication) during the therapeutic trial.
|
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
|
Aberrant Behavior Checklist Scale - Social Withdrawal Subscale.
Exploring aberrant, stereotyped, repetitive and obsessive behaviours (sub-scores and total score) and co-morbidities
|
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
|
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
|
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
|
Evaluate the effect of the treatment on the global functioning of patients and the impact on their environment
|
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
|
Surrounding Constraints - Caregiver Strain Index.
Evaluate the effect of the treatment on the global functioning of patients and the impact on their environment
|
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
|
Monitoring suicide risk and suicidal risk via the Columbia Suicide Severity Rating Scale (C-SSRS)
|
Baseline (At randomization)and 12 weeks
|
Collaborators and Investigators
Investigators
- Principal Investigator: Delorme Richard, PHD, APHP
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Neurodevelopmental Disorders
- Autistic Disorder
- Autism Spectrum Disorder
- Child Development Disorders, Pervasive
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Enzyme Inhibitors
- Tranquilizing Agents
- Psychotropic Drugs
- Antidepressive Agents
- Antimanic Agents
- Lithium Carbonate
Other Study ID Numbers
- P160914
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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