Clinical Research Directory

Natural History Study of GEMIN-5 Related Neurodevelopmental Disorder

This study will include a comprehensive retrospective chart review and a longitudinal prospective observational natural history study to characterize the phenotypic spectrum of GEMIN5-Related Neurodevelopmental Disorder. We aim to define the trajectory of this ultra-rare disease, core clinical features, characteristics at disease onset and diagnosis, neurological symptomatology, and neuroimaging findings over time. In this study, biological specimens (serum) will also be collected in a biorepository for translational research purposes.

Rett Syndrome Registry

The Rett Syndrome Registry is a longitudinal observational study of individuals with MECP2 mutations and a diagnosis of Rett syndrome. Designed together with the IRSF Rett Syndrome Center of Excellence Network medical directors, this study collects data on the signs and symptoms of Rett syndrome as reported by the Rett syndrome experts and by the caregivers of individuals with Rett syndrome. This study will be used to develop consensus based guidelines for the care of your loved ones with Rett syndrome and to facilitate the development of better clinical trials and other aspects of the drug development path for Rett syndrome.

The Genetics Navigator: Evaluating a Digital Platform for Genomics Health Services

Genetic testing (GT) (including targeted panels, exome and genome sequencing) is increasingly being used for patient care as it improves diagnosis and health outcomes. In spite of these benefits, genetic testing is a complex and costly health service. This results in unequal access, increased wait times and inconsistencies in care. The use of e-health tools to support genetic testing delivery can result in a better patient experience and reduced distress associated with waiting for results and empower patients to receive and act on medical results. We have previously developed and tested an interactive, adaptable and patient-centred digital decision support tool (Genetics ADvISER) to be used for genetic testing decision making, and have now developed the Genetics Navigator (GN), a patient-centred e-health navigation platform for end-to-end genetic service delivery. The objective of this study is to evaluate the effectiveness of the GN in an RCT in reducing distress with patients and parents of patients being offered genetic testing. Results of this trial will be used to establish whether the GN is effective to use in practice. If effective, GN could fill a critical clinical care gap and improve health outcomes and service use by reducing counselling burden as well as overuse, underuse and misuse of services. These are concerns policy makers seek to address through the triple aims of health care1. This study represents a significant advance in personalized health by assessing the effectiveness of this novel, comprehensive e-health platform to ultimately improve genetic service delivery, accessibility, patient experiences, and patient outcomes.

Platform for the Prospective Mother-child Study of the Determinants of Neurodevelopmental Disorders

Neurodevelopmental disorders such as attention deficit disorder with or without hyperactivity, autism spectrum disorder, language and social communication disorder, motor coordination disorder, learning disorder (dyslexia, dyscalculia, dysorthography), intellectual development disorder are frequent and long-lasting developmental difficulties that can be observed in children in various domains. They are often associated and have a significant impact on daily functioning at school and at home. The rate of people affected by neurodevelopmental disorders including autism spectrum disorder have increased significantly over the past 20 years. Improved screening only partly explains this evolution. A genetic predisposition plays an important role in the occurrence of these disorders, however, current scientific data suggest a multifactorial origin. Exposures such as those related to the use of pesticides, air pollution or the presence of endocrine disruptors in our diet could be involved in the genesis of neurodevelopmental disorders, particularly during intrauterine life, a period of great vulnerability. The current diagnostic pathways for autism rarely enable the early identification of babies at risk. Without early detection and timely targeted intervention, these children have a poor health outcome and do not reach their full potential. The general objective of the MARIANNE cohort is to constitute a French research infrastructure dedicated to research on the biological and environmental determinants of neurodevelopmental disorders including autism. This cohort is based on the follow-up of 1200 families with already a child affected by an autism spectrum disorder, which implies a high risk of neurodevelopmental disorders including autism spectrum disorder for the siblings, and of 500 families from the general population with no excess risk of neurodevelopmental disorders. The total number of subjects to be included (mother, father, unborn child and ASD sibling for the HR group) is thus 6300. The inclusion of these families will be at the beginning of a new pregnancy and the follow-up will be carried out from the second trimester of pregnancy until the children are 6 years old, the age at which the diagnosis of neurodevelopmental disorders is possible. Biological, clinical, social and environmental data will be collected at different stages of the follow-up and will be included into a large database.

Targeting Human Milk Fortification to Improve Preterm Infant Growth and Brain Development

This study is a randomized trial comparing 2 methods of human milk fortification for preterm infants in the neonatal intensive care unit (NICU). All participating infants will receive a human milk diet comprising maternal and/or donor milk plus multi-component and modular fortifiers. In one group (control), the milk will be fortified according to routine standard of care. In the other group (intervention), the fortification will be individually targeted based on the results of point-of-care human milk analysis. Outcomes include physical growth in the NICU and after discharge, brain structure by magnetic resonance imaging at term equivalent age, and neurodevelopment at 2 years.

Homelessness and Prevalence of Neurodevelopmental Disorders

Introduction \& Central question: Psychiatric disorders are highly prevalent in the homeless population, however neurodevelopmental disorders are also at risk of leading to homelessness (Churchard et al., 2018; Casey et al., 2020). Research on this topic is poor in France. This research aims to study the prevalence in France of 3 neurodevelopmental disorders (NDDs) in a homeless population (Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder and Intellectual Developmental Disorder). Methods / approach: A 2 phase approach will be used including a screening phase and a diagnosis phase. This research is a pilot study that will include 150 homeless people, over 2 years. The assessment involves combining the results from standardised self-report tools, direct observation and informant-report, thus guaranteeing an objective and thorough diagnosis. This approach gives a better picture of actual behaviour but also a better understanding of the person's development. OUTCOME: This study will give insight on how to better understand the profile of the homeless population in France, and the prevalence of autism in this population. It will also bring valuable knowledge on how autism and other NDDs can impact one's path in life and lead to homelessness. The results can help develop targeted cares and measures for homeless people with NDDs.

Neuraxial Labor Analgesia and Offspring Neurodevelopment

How perinatal factors affect the long-term development of children has always been an issue of much concern. This study is designed to explore the potential impact of maternal neuraxial labor analgesia exposure on offspring neurodevelopment.

Perinatal Covid-19 Infection, NO Pathway, and Minipuberty

Some evidence exists that SARS-COV-2 may infect pituitary axis, and therefore may alter hypothalamic function. Whether perinatal COVID-19 is associated with alterations in the maturation of the Hypothalamic-Pituitary-Gonadal (HPG) axis, and specifically with its transient activation occurring during infancy, namely minipuberty, is a major concern. Among the various pathogenic features related to COVID-19, altered minipuberty could be a key factor underlying many multimorbidities later in life, suggesting that they could involve a common causative mechanism that occurs within this short and critical period of time following birth. Altered minipuberty together with NO deficiency seem to be key factors underlying many of these multimorbidities, suggesting that they involve a common causative mechanism that occurs within this short and critical period of time following birth

Robot Asissted Training on Neurodevelopmental Alterations

The aim of this randomized crossover clinical trial is to determine the effect of robot assisted gait training combined with physiotherapy on body composition and functional variables in a pediatric population with neurodevelopmental disorders.The main questions to answer are: * Does this treatment improve body composition parameters? * Does the treatment help maintaining functionality and without causing discomfort or pain? Participants will perform 2 weekly physiotherapy sessions for 8 weeks, then there will be 4 weeks of washout, afer which each patient will cross over to the other group for 8 more weeks.

Effectiveness of the COPCA Program in Infants at Risk of Neurodevelopmental Disorders

The purpose of this clinical trial is to evaluate whether the COPCA® program (Coping with and Caring for Infants with Special Needs) is more effective than conventional pediatric physiotherapy and parent education in improving development in infants at risk of neurodevelopmental disorders, as well as empowering their families. This study will include infants younger than 12 months of corrected age who are at risk of neurodevelopmental disorders and are currently receiving early intervention or pediatric physiotherapy services, together with their parents or primary caregivers. The main questions this study aims to answer are: Does the COPCA® program improve motor development and functional abilities in infants at risk of neurodevelopmental disorders more than conventional pediatric physiotherapy or parent education? Does the COPCA® program increase family empowerment and improve parents' perception of the care they receive compared with traditional intervention models? The researchers will compare outcomes across four study groups: In-person COPCA® intervention Online COPCA® intervention Parent education group Conventional pediatric physiotherapy group Participants will be randomly assigned to one of the four groups. The intervention period will last 6 months, with assessments conducted at the start of the study, during the intervention, and during follow-up. Infants will take part in age-appropriate daily activities and play situations. Parents or caregivers will actively participate in the intervention sessions and will be supported in learning how to promote their child's development during everyday routines. The study will assess infant motor development, functional abilities, overall development, family empowerment, and parents' perception of family-centered care using validated assessment tools and interviews. The results of this study may help improve early intervention strategies for infants at risk of neurodevelopmental disorders and support more family-centered approaches to care.

Safety and Efficacy of tPBM for Epileptiform Activity in Autism

For this study, the proposed intervention will be noninvasively delivered near infra-red (NIR) light - transcranial Photobiomodulation (tPBM) - to the brains of autistic children with abnormal EEGs with epileptiform discharges or with epilepsy. This will occur, twice a week, for 10 weeks. The NIR light is delivered to specific brain areas by Cognilum, a wearable device developed by Jelikalite. The expected outcome is improved focus, improved eye contact, improved speech, improved behavior, and gains in functional skills. Cognilum may impact the clinical practice of treating autism. At the beginning, at five weeks, and at the end of study, the clinician will complete the CARS-2, SRS, CGI, and a caregiver interview; additionally, questionnaires will be administered to caregivers during one of the 1-hour weekly treatment sessions.

Patterns of Neurodevelopmental Disorders

The purpose of this study is to systematically evaluate the results of medical investigations to identify symptom and biological patterns and common etiologies of neurodevelopmental disorders.

Characterization of Social Cognition Profiles in Children and Adolescents With Neurodevelopmental Disorders: a Clinical Study Using a Multidimensional Battery

In France, more than one in ten school-aged children suffers from a mental health disorder, and half of these disorders appear before the age of 14. Yet, only half of affected children receive appropriate support. At the cognitive level, it is now widely accepted by the scientific community that strong socio-cognitive skills protect against the emergence of certain disorders. Social cognition skills, crucial for development and social integration, are often underestimated in clinical neuropsychology, particularly due to the lack of validated assessment tools for children. The challenges related to the clinical assessment of social cognition in children and adolescents are therefore significant, especially since specific deficits are likely to be associated with numerous developmental pathologies and psychiatric disorders (neurodevelopmental disorders, mood disorders, anxiety disorders, psychotic disorders). However, these disorders are insufficiently assessed. A more precise characterization would allow for the identification of therapeutic targets specific to each neurodevelopmental disorder. Therefore, this research aims to address this lack of tools by using a multidimensional assessment battery of social cognition in children and adolescents aged 8 to 16, evaluating four fundamental domains of social cognition: emotion processing, social perception, theory of mind, and attributional style. This multidimensional assessment battery of social cognition is developed by the Child and Adolescent Psychiatry Department of Necker-Enfants Malades Hospital.

n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum

This study aims to investigate the associations of maternal nutritional status during pregnancy and postpartum periods with postpartum abnormal glucose metabolism in Guangzhou pregnant women. Additionally, it seeks to explore the relationships between maternal nutritional status (pre- and postnatal) and offspring health outcomes, including physical growth, neurodevelopment, and common childhood diseases.

High Depth Exome Sequencing on DNA From a Salivary Sample by Mouth Smear.

Despite technological advances, a genetic etiology has been identified in only about 50% to 60% of patients with Neurodevelopmental disorders (NDDs), with a higher diagnostic yield in the syndromic NDD and IDD subgroups. However, identifying a precise etiological diagnosis is essential to optimize patient care, clarify their prognosis, consider targeted therapies, refer families to appropriate resources and support, and provide genetic counseling to relatives. The tests typically offered as part of the etiological assessment of syndromic NDDs and IDD include DNA microarray analysis, testing for fragile X syndrome and genome sequencing from a blood sample. When this assessment remains negative, the cause usually remains unknown. Mosaic genomic abnormalities (or post-zygotic variations) are a common cause of negative results in current diagnostic genetic tests and represent a field of research that has yet to be fully explored outside of skin disorders. Identifying mosaic genomic abnormalities remains technically complex due to the difficulty of detecting low levels of mosaicism and limited access to the tissue of interest when the variation is absent from blood tissue. High-depth exome sequencing is the technique of choice for detecting low levels of mosaicism. In the case of NNDs, as the affected tissue is not available, the buccal epithelium is an interesting alternative to blood, as it is easily accessible and inexpensive. The objective of our study is to evaluate the diagnostic yield of high-depth exome sequencing technology on a DNA extracted from a buccal swab in the etiological assessment of patients with IDD or syndromic NDD whose reference analysis (genome sequencing on blood) proved inconclusive.

The Relationship Between Reaction Time and Motor Skills in Children With Pervasive Developmental Disorders

This study examines whether the relationship between reaction time and motor skills differs between children aged 3-6 with pervasive developmental disorders and typically developing peers. It aims to determine the direction and strength of this relationship in children with developmental disorders and compare it with that of typically developing children, thereby providing evidence on how cognitive processing speed and motor performance interact in early childhood under developmental disorder conditions.

Intranasal Insulin for Autism Spectrum Disorder in Children and Young Adults Aged 4 to 21 Years

This observational study evaluates the real-world use of intranasal insulin in children and young adults with autism spectrum disorder (ASD) utilizing the ViaNase™ device developed by Kurve Therapeutics. Intranasal insulin represents an off label use of an FDA approved medication and is prescribed by participants' treating healthcare providers as part of routine clinical care. Insulin is a hormone involved in cerebral energy metabolism and may play a role in cognitive processes such as learning, memory, and behavior. Emerging research suggests that intranasal delivery using specialized delivery systems such as ViaNase™ may facilitate transport along olfactory and trigeminal pathways, potentially allowing insulin to reach central nervous system targets. This delivery approach has been associated in early studies with changes in social communication and functional outcomes in individuals with neurodevelopmental conditions. This study will follow approximately 12 participants between the ages of 4 and 21 years who are already receiving, or planning to receive, intranasal insulin as part of their standard clinical care using the ViaNase™ device. This is a non-interventional observational study; no treatment is assigned or provided by the study team. Participants will be monitored over an approximate 6-month period for changes in autism-related symptoms, including social interaction, communication, repetitive behaviors, and overall functional development. In addition, safety data will be collected, including tolerability and any reported adverse events. The primary objective of this study is to generate real-world evidence to better characterize the safety profile and potential functional effects of intranasal insulin delivered via ViaNase™ in individuals with ASD, and to inform the design of future controlled clinical investigations.

Motor-voice Assessment in Infants (MAMI)

The goal of this observational study is to discover features of normal and disordered motor-voice profiles that are biobehavioral markers of physical disability in infants.. The main questions it aims to answer are: Identify voice factors among infants with newborn-detectable risk. Identify association between individual characteristics (Gestational age at birth, global function, motor-function) and voice factors. Examine unique features of voice production that are present in infants with high-risk for Cerebral Palsy (CP). Participants will be asked to upload a 3-minute videos of their child at term-age, 3.5-, and 9-months of age. At the 3.5-month and 9-month time point parents can choose to attend an optional in-person assessment with their child.

Intensive Multimodal Neurorehabilitation Targeting Neuroplasticity in Pediatric Neurodevelopmental and Chromosomal Disorders

This observational study evaluates functional and developmental outcomes in pediatric participants undergoing a two week intensive multimodal neurorehabilitation program. The program is designed for children with neurodevelopmental disorders, including but not limited to cerebral palsy, autism spectrum disorder, developmental delay, hypoxic ischemic encephalopathy (HIE), and chromosomal or genetic abnormalities. Participants receive individualized therapy sessions for approximately 2.5 hours per day over a two week period. The intervention is not standardized but is tailored to each child's specific needs and may include components such as sensory integration, motor planning, reflex integration, oculomotor training, executive functioning activities, communication support, and other brain based therapeutic approaches. The purpose of this study is to observe changes in functional abilities, including attention, motor coordination, emotional regulation, communication, and activities of daily living. Outcomes are assessed using clinician observation and parent reported changes before and after the intensive program, with limited follow-up when available. This study does not assign participants to a specific treatment as part of a research protocol. Instead, it collects real world data from children already participating in a clinical therapy program to better understand potential benefits of intensive, individualized neurorehabilitation approaches.

Growing Up in Multifactorial Risk Conditions

The perinatal period brings significant physiological and emotional changes in mothers, linked to pregnancy, childbirth, and caring for a newborn. While pregnancy is often experienced positively, various stressors can impact maternal well-being and child health. Maternal stress can lead to vascular issues (e.g., hypertension, preeclampsia) or mental health concerns like depression and anxiety. Recent studies show depressive symptoms occur in 41.45% of women in the first trimester, with clinical depression in 9.85%. Postpartum depression has an estimated incidence of 10-20%, with strong continuity from prenatal depression. Stressors, including adverse childhood experiences (ACEs) and maternal psychological issues, often lead to emotional dysregulation. This, through intergenerational transmission, can impact a child's emotional regulation into adolescence. Intergenerational transmission involves both biological mechanisms (endocrine, neurophysiological, epigenetic) and social mechanisms (parenting style, early relationship quality). Sensitive, reciprocal adult-child interactions are essential for socio-emotional and cognitive development, and a child's emotional regulation abilities predict later emotional-behavioral issues. Understanding perinatal risk predictors is key to developing programs that reduce such risks. For example, factors like ACEs, unfavorable conditions, complications during pregnancy, and neurodevelopmental challenges in children can negatively affect the child's cognitive, emotional, and behavioral functioning, maternal well-being, epigenetic changes, and dyadic synchrony. Yet, risk factors do not prevent adaptation and may coexist with protective factors that support maternal well-being and child development. Early parenting support is thus essential, particularly in cases with multiple risks. Research indicates that challenges in implementing support programs often arise from insufficient identification of women at risk of psychological distress during pregnancy and postpartum. In many cases, these issues go unrecognized and untreated, or intervention happens late. It is crucial that prenatal screenings assess potential risk factors to identify women who could benefit from psychological and parenting support starting early in pregnancy. Such multidisciplinary interventions aim to limit intergenerational transmission of mental health issues, reducing impact on a child's emotional, behavioral, and cognitive development. Evidence increasingly supports that Home Visiting (HV) programs benefit both maternal mental health and child development. These programs help mothers manage psychopathological risks and parenting stress while fostering strong attachment and interactions that promote the child's emotional-behavioral development. Primary Objectives To investigate, at 18 months of child age (adjusted for prematurity), whether for mothers with perinatal risk, an HV-based parenting support intervention affects: 1.1. The child's emotional-behavioral profile, using the Child Behavioral Checklist 1.5/5 (CBCL); 1.2. Maternal mental well-being, using the Mental Health Continuum-Short Form (MHC-SF). Secondary Objectives Considering cumulative perinatal risk factors, examine if the HV program: 2.1. Increases maternal well-being for the ACE+ group from T0 (pre-intervention, first trimester) to T8 (post-intervention, child at 18 months); 2.2. Promotes mother-child synchrony at 3 months, in relational functioning (mother-child behavior) and cardio-respiratory activity (HRV and RSA); 2.3. Enhances child developmental competencies at 3 and 18 months (domains: (1) motor, (2) adaptive behaviors, (3) socio-emotional, (4) cognitive, (5) communication). Exploratory Objectives Examine if the HV program influences the epigenetic status of mothers (pre- and postnatal) and children (at 3 months). DNA methylation variations will be assessed in mothers and children in the HV program group versus controls, focusing on target genes related to stress regulation (SLC6A4, NR3C1, BDNF), neural plasticity (BDNF), social interaction (DRD4, OXTR), and tactile stimulation perception (Piezo1, Piezo2, TRPV1, TRPM8, MRGPRB4). Additional candidate genes will be identified through computational research.

Reducing Missed Appointments

There are four goals of this project: (1) To examine the impact of different appointment reminder messages on appointment attendance; (2) to determine the added benefit of a patient navigator reaching out in advance of appointments to families at elevated risk of missing their appointment, and determine the most common barriers families face in appointment attendance; (3) to evaluate which patients are at highest risk of missing their appointment, and to determine the effectiveness of the intervention trial across different patient risk levels; and (4) to examine if the missing appointment interventions increase the socioeconomic diversity patients.

Effect of Probiotics on the Intestinal Microbiota of Pediatric Patients

Numerous studies have described an altered gut microbiota composition (dysbiosis) in patients with neurodevelopmental disorders that can be correlated with their symptoms, especially gastrointestinal symptoms. An interventional, randomised, double-blind, placebo-controlled study will be conducted to investigate the effect of a probiotic supplement on the microbiota composition of children aged 3-7 years with neurodevelopmental issues. The duration of the study will be of 6 months approximately, including 6 months of product intake. Participants will be randomly assigned to one of the two study groups: control group with placebo administration or probiotic administration group.

Physical Activity and Community EmPOWERment Project

Purpose: Conduct a wait-list randomized controlled trial (RCT) of an inclusive physical activity program called PACE for adults with intellectual disability (ID) who are not yet showing signs of Alzheimer's Disease (AD)/age-related dementias (ARD). Participants: Participants include 120 adults with ID, their caregivers, and their coaches (up to 360 individual participants, grouped as triads), recruited through the University of North Carolina at Chapel Hill and the University of Arkansas. Participants also include 16 exercise professionals. Procedures (methods): Each cohort will include 20 triads who are randomly assigned to the PACE program or the waitlist control group.

Innovative Methodologies for Neuroplasticity in Developmental Age With the Use of Virtual Reality

Neurodevelopmental disorders, such as Cerebral Palsy (CP), Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), are complex conditions that affect various aspects of children's development. Despite advancements in treatments, conventional rehabilitative interventions tend to focus on specific aspects, often overlooking the holistic needs of the patient. Many of these interventions fail to engage children, who may feel uninvolved or demotivated. Innovative technologies, such as immersive virtual reality (IVR), offer a promising alternative to make rehabilitation more engaging and comprehensive. This study aims to evaluate the effects of IVR-based rehabilitation on children and adolescents with neurodevelopmental disorders, focusing on improvements in cognitive, motor, and social functions. We hypothesize that IVR will enhance social interaction, attention, motor skills, and overall quality of life. The study will include children and adolescents aged 8 to 18 years, diagnosed with ADHD, ASD, and cerebral palsy. The CAR-EN platform, which provides a highly customizable therapeutic environment, will be used. Assessments will measure cognitive, motor, and social skills before and after the intervention. We expect immersive virtual reality to lead to significant improvements in the participants' cognitive, motor, and social abilities. These findings could potentially contribute to a shift in therapeutic guidelines, offering more effective treatments for children with neurodevelopmental disorders.