Autism Spectrum DisorderREGAINNCT06169111
REGulatory T Cells in Autism Induced by Maternal Immune Activation
A study testing REGulatory T cells in Autism induced by maternal Immune activation in people with Autism Spectrum Disorder, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Autism Spectrum Disorders (ASD) represent a heterogeneous clinical entity of neurodevelopmental disorders affecting around 1% of the general population (Lord et al. 2020). There is currently no curative treatment for patients with ASD, and management does not take into account the existence of specific patient… Read more about this study
- Who is it for?
- Ages 3 to 15 yearsHealthy volunteers can take part
- Conditions the study is for
- Autism Spectrum Disorder
- What is being tested?
- REGulatory T cells in Autism induced by maternal Immune activation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jan 2024to 1 Jan 2026
- Phase
- Interventional
- 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 3 to 15 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Patients with positive diagnosis of ASD according to DSM-5 (APA, 2015);
- Age at inclusion between 3 and 15 years;
- Informed consent signed by both parents and oral agreement in principle given by the subject;
- Patients affiliated to a social security system
Who cannot join
- Patients with severe/profound intellectual disability;
- Uncontrolled epileptic seizures;
- Maternal infection during pregnancy with a pathogen with a known direct cerebral cytotoxic effect (CMV);
Trial locations and contacts
1 site in 1 country.
France1 site
Robert Debré Hospital
Paris, 75019
Richard DELORME, MD, PhD, +331.40.03.41.30, richard.delorme@aphp.fr
Pierre ELLUL, MD, PhD, +331.40.03.41.31, pierre.ellul@aphp.fr
About this study
Autism Spectrum Disorders (ASD) represent a heterogeneous clinical entity of neurodevelopmental disorders affecting around 1% of the general population (Lord et al. 2020). There is currently no curative treatment for patients with ASD, and management does not take into account the existence of specific patient subgroups. Beyond genetic factors (Delorme et al. 2013), environmental factors play a fundamental role in the determinism of ASD. Among them, maternal immune activation (MIA) during pregnancy is a recognized risk factor for ASD in children (Estes and McAllister 2016). Our team has helped to demonstrate that MIA induced by infections or autoimmune pathologies in the mother during pregnancy (particularly at the end of the 1st trimester/beginning of the 2nd trimester) significantly increases the risk of ASD in the offspring (Antoun et al. 2021). Mechanistically, MIA leads to a deregulation of the regulatory T lymphocyte (Tregs)/Th17 balance (in the direction of a decrease in anti-inflammatory Tregs and an increase in pro-inflammatory Th17) in the mother but also, via epigenetic mechanisms, in the fetus (Lim et al. 2021). Our team have recently demonstrated the same Tregs/Th17 deregulation profile in ASD patients (Ellul et al. 2021). This disruption of the Tregs/Th17 balance is responsible for disrupting fetal brain development via IL-17 receptors present on fetal neurons (Choi et al. 2016). Importantly, these socio-communicative and morphological abnormalities appear, in specific animal models, to be reversible upon restoration of the Tregs/Th17 balance (Z. Xu et al. 2021; Choi et al. 2016). While data on the involvement of IL-17 are becoming better known, the role of Tregs in this model has been surprisingly little studied.Our overall aim is therefore, in humans and mice, to determine the role of Tregs and IL-17-producing lymphocytes in the development and maintenance of autistic symptoms triggered by MIA.
Our specific objectives in humans will be to use an existing cohort (EXPECT) of ASD patients to compare those with and without a history of MIA using a standardized clinical evaluation (including overall autism severity, language and motor development, adaptive behaviors,comorbidities), a systems immunology assessment (combining deep immunophenotyping by flow cytometry, cytokine measurements - simultaneous Luminex assay of 50 pro-inflammatory cytokines associated with Th1/Th2/Th17/Treg responses) and a targeted quantitative metabolomics analysis of the tryptophan pathway.
Read the detailed description
The aim of the REGAIN project will be to study in detail the cellular populations involved in the development of MIA-mediated autistic symptoms in humans.
Based on both our preliminary meta-analysis data and previous work on Tregs work on Tregs, our team calculated that the number of subjects needed to meet our primary objective on Tregs was (with risk α = 0.05, power power 1 - β =0.9 and a minimum detectable odds ratio = 5) of 30 patients per group (3.75 p/month for 24 months).
The Center of Excellence for Autism and Neurodevelopmental Disorders (InovAND) at Robert Debré Hospital receives around 500 new ASD patients a year (40p/month). Furthermore, in humans, it is estimated that 15% of autisms could be linked to an ASI. Over the period of our study, this should represent around 75 patients/year (7p/month) at Robert Debré. For safety reasons, to include enough patients but taking into account the drop in activity due to the COVID-19 crisis, our team decided to include decided to include 35 patients/group (4.37 p/month for 24 months = 1.45 p/month/group).
During hospitalization for the diagnostic workup at InovAND (Robert Debré hospital), and as part of the care provided, patients will be assessed by psychiatrists specializing in autism who will take a family history, ascertain the presence or absence of MIA, collect the child's personal and neurodevelopmental history, and obtain parental consent for inclusion in the cohort. Psychologists, speech therapists and psychomotor therapists will then assess the patients using the standardized scales described above. If the parents have given their consent to participate in REGAIN, the patients will have a sample taken for the purposes of the research. blood sample at the end of the clinical evaluation.
As part of standard care, each child will benefit from a standardized assessment based on (i) autism reference interviews; the Social Reciprocity Scale (SRS); (ii) the Autism Diagnostic Interview (ADI) Autism Diagnostic Observation (iii) assessment of general cognitive abilities and adaptive behavior profile (Wechsler scales or Raven's progressive matrices for non-verbal individuals, Vineland II scale); (iv) a special effort will be made to characterize the main symptoms of autism. More specifically, repetitive behaviors and sensory abnormalities will be explored using the Repetitive Behavior Scales (revised version) and Dunn's Sensory Profile. (v) Psychiatric and somatic comorbidities associated with immune dysregulation will also be explored (ADHD, chronic tics frequently reported in PANS syndrome, gastrointestinal symptoms, immunoallergic comorbidities) using a semi-structured interview our team have constructed.
Characterization of maternal history of MIA: Due to the intrinsic nature of our study design, Our team will not be able to prospectively explore ASI during pregnancy in mothers. Therefore, our team will include patients in the MIA+ category if their mother had a significant history suggestive of MIA during pregnancy.
As previously mentioned, the children included in REGAIN are part of a larger cohort of children with ASD (also including healthy controls) followed at the Robert Debré Hospital (EXPECT and C0733 studies), for which our team already have the agreement of a French personal protection committee for the collection of clinical data and immunological samples from ASD patients (IDRCB no. IDRCB: 2021-A00489-32; Ref. CPP: 2021-27) and controls (authorization no. 917138). The purpose of this protocol and the accompanying request is to authorize the collection of fresh blood and the realization of new research objectives.
- Conditions
- Autism Spectrum Disorder
- Being tested
- REGulatory T cells in Autism induced by maternal Immune activation
- Keywords
- neurodevelopemental disorders, immunology, regulatory T lymphocytes
- Medical subject headings
- Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
REGulatory T cells in Autism induced by maternal Immune activationBiological
REGulatory T cells in Autism induced by maternal Immune activation
| Study group | Role | What they receive |
|---|---|---|
| Autism Spectrum Disorders (ASD) patients with Maternal Immune Activation (MIA) | Experimental | Not described Receives: Biological: REGulatory T cells in Autism induced by maternal Immune activation |
| Autism Spectrum Disorders (ASD) patients without Maternal Immune Activation (MIA) | Active comparator | Not described Receives: Biological: REGulatory T cells in Autism induced by maternal Immune activation |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare Tregs count (% CD4+) and Th17 count (% CD3+) and their ratio in ASD patients with and without MIA
Evaluation of the Tregs count/Th17 balance in ASD patients with and without MIA
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2023
- Study start1 Jan 2024 (estimated)
- Primary completion1 Jan 2025 (estimated)
- Study completion1 Jan 2026 (estimated)
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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Richard DELORME, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06169111
- Sponsor's protocol ID
- APHP230622
- Other IDs
- IDRCB: 2023-A01329-36
- Acronym
- REGAIN
- Status last verified
- Nov 2023
- First submitted
- 24 Nov 2023
- Last updated
- 13 Dec 2023
- 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 13 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- REGulatory T Cells in Autism Induced by Maternal Immune Activation
- ClinicalTrials.gov ID
- NCT06169111
- Acronym / sponsor ID
- REGAIN / APHP230622
- Conditions
- Autism Spectrum Disorder
- Keywords
- neurodevelopemental disorders, immunology, regulatory T lymphocytes
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 1 Jan 2024 (estimated)
- Primary completion
- 1 Jan 2025 (estimated)
- Study completion
- 1 Jan 2026 (estimated)
- First posted
- 13 Dec 2023 (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.
Autism Spectrum Disorders (ASD) represent a heterogeneous clinical entity of neurodevelopmental disorders affecting around 1% of the general population (Lord et al. 2020). There is currently no curative treatment for patients with ASD, and management does not take into account the existence of specific patient subgroups. Beyond genetic factors (Delorme et al. 2013), environmental factors play a fundamental role in the determinism of ASD. Among them, maternal immune activation (MIA) during pregnancy is a recognized risk factor for ASD in children (Estes and McAllister 2016). Our team has helped to demonstrate that MIA induced by infections or autoimmune pathologies in the mother during pregnancy (particularly at the end of the 1st trimester/beginning of the 2nd trimester) significantly increases the risk of ASD in the offspring (Antoun et al. 2021). Mechanistically, MIA leads to a deregulation of the regulatory T lymphocyte (Tregs)/Th17 balance (in the direction of a decrease in anti-inflammatory Tregs and an increase in pro-inflammatory Th17) in the mother but also, via epigenetic mechanisms, in the fetus (Lim et al. 2021). Our team have recently demonstrated the same Tregs/Th17 deregulation profile in ASD patients (Ellul et al. 2021). This disruption of the Tregs/Th17 balance is responsible for disrupting fetal brain development via IL-17 receptors present on fetal neurons (Choi et al. 2016). Importantly, these socio-communicative and morphological abnormalities appear, in specific animal models, to be reversible upon restoration of the Tregs/Th17 balance (Z. Xu et al. 2021; Choi et al. 2016). While data on the involvement of IL-17 are becoming better known, the role of Tregs in this model has been surprisingly little studied.Our overall aim is therefore, in humans and mice, to determine the role of Tregs and IL-17-producing lymphocytes in the development and maintenance of autistic symptoms triggered by MIA.
Our specific objectives in humans will be to use an existing cohort (EXPECT) of ASD patients to compare those with and without a history of MIA using a standardized clinical evaluation (including overall autism severity, language and motor development, adaptive behaviors,comorbidities), a systems immunology assessment (combining deep immunophenotyping by flow cytometry, cytokine measurements - simultaneous Luminex assay of 50 pro-inflammatory cytokines associated with Th1/Th2/Th17/Treg responses) and a targeted quantitative metabolomics analysis of the tryptophan pathway.
Detailed description
The aim of the REGAIN project will be to study in detail the cellular populations involved in the development of MIA-mediated autistic symptoms in humans.
Based on both our preliminary meta-analysis data and previous work on Tregs work on Tregs, our team calculated that the number of subjects needed to meet our primary objective on Tregs was (with risk α = 0.05, power power 1 - β =0.9 and a minimum detectable odds ratio = 5) of 30 patients per group (3.75 p/month for 24 months).
The Center of Excellence for Autism and Neurodevelopmental Disorders (InovAND) at Robert Debré Hospital receives around 500 new ASD patients a year (40p/month). Furthermore, in humans, it is estimated that 15% of autisms could be linked to an ASI. Over the period of our study, this should represent around 75 patients/year (7p/month) at Robert Debré. For safety reasons, to include enough patients but taking into account the drop in activity due to the COVID-19 crisis, our team decided to include decided to include 35 patients/group (4.37 p/month for 24 months = 1.45 p/month/group).
During hospitalization for the diagnostic workup at InovAND (Robert Debré hospital), and as part of the care provided, patients will be assessed by psychiatrists specializing in autism who will take a family history, ascertain the presence or absence of MIA, collect the child's personal and neurodevelopmental history, and obtain parental consent for inclusion in the cohort. Psychologists, speech therapists and psychomotor therapists will then assess the patients using the standardized scales described above. If the parents have given their consent to participate in REGAIN, the patients will have a sample taken for the purposes of the research. blood sample at the end of the clinical evaluation.
As part of standard care, each child will benefit from a standardized assessment based on (i) autism reference interviews; the Social Reciprocity Scale (SRS); (ii) the Autism Diagnostic Interview (ADI) Autism Diagnostic Observation (iii) assessment of general cognitive abilities and adaptive behavior profile (Wechsler scales or Raven's progressive matrices for non-verbal individuals, Vineland II scale); (iv) a special effort will be made to characterize the main symptoms of autism. More specifically, repetitive behaviors and sensory abnormalities will be explored using the Repetitive Behavior Scales (revised version) and Dunn's Sensory Profile. (v) Psychiatric and somatic comorbidities associated with immune dysregulation will also be explored (ADHD, chronic tics frequently reported in PANS syndrome, gastrointestinal symptoms, immunoallergic comorbidities) using a semi-structured interview our team have constructed.
Characterization of maternal history of MIA: Due to the intrinsic nature of our study design, Our team will not be able to prospectively explore ASI during pregnancy in mothers. Therefore, our team will include patients in the MIA+ category if their mother had a significant history suggestive of MIA during pregnancy.
As previously mentioned, the children included in REGAIN are part of a larger cohort of children with ASD (also including healthy controls) followed at the Robert Debré Hospital (EXPECT and C0733 studies), for which our team already have the agreement of a French personal protection committee for the collection of clinical data and immunological samples from ASD patients (IDRCB no. IDRCB: 2021-A00489-32; Ref. CPP: 2021-27) and controls (authorization no. 917138). The purpose of this protocol and the accompanying request is to authorize the collection of fresh blood and the realization of new research objectives.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Autism Spectrum Disorders (ASD) patients with Maternal Immune Activation (MIA) | Experimental | Biological: REGulatory T cells in Autism induced by maternal Immune activation |
| Autism Spectrum Disorders (ASD) patients without Maternal Immune Activation (MIA) | Active comparator | Biological: REGulatory T cells in Autism induced by maternal Immune activation |
Who may qualify
- Ages
- 3 to 15 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Patients with positive diagnosis of ASD according to DSM-5 (APA, 2015);
- Age at inclusion between 3 and 15 years;
- Informed consent signed by both parents and oral agreement in principle given by the subject;
- Patients affiliated to a social security system
Key exclusion criteria (3 listed)
- Patients with severe/profound intellectual disability;
- Uncontrolled epileptic seizures;
- Maternal infection during pregnancy with a pathogen with a known direct cerebral cytotoxic effect (CMV);
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 |
|---|---|---|
| REGulatory T cells in Autism induced by maternal Immune activationREGulatory T cells in Autism induced by maternal Immune activation | Biological | Autism Spectrum Disorders (ASD) patients with Maternal Immune Activation (MIA), Autism Spectrum Disorders (ASD) patients without Maternal Immune Activation (MIA) |
Primary outcome
To compare Tregs count (% CD4+) and Th17 count (% CD3+) and their ratio in ASD patients with and without MIA
Time frame: 24 months
Evaluation of the Tregs count/Th17 balance in ASD patients with and without MIA
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2023.
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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.
Richard DELORME, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing REGulatory T cells in Autism induced by maternal Immune activation 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 4 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 13 Dec 2023. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Richard DELORME, MD, PhD (+331.40.03.41.30, richard.delorme@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To compare Tregs count (% CD4+) and Th17 count (% CD3+) and their ratio in ASD patients with and without MIA (time frame: 24 months). 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 13 Dec 2023.