Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) Clinical Trial
Official title:
Clinical, Laboratory, and Biomedical Characterization of Pediatric Acute-onset Neuropsychiatric Syndrome (PANS)
Background:
PANS is an illness that comes on suddenly in children. The full name is Pediatric Acute-Onset
Neuropsychiatric Syndrome. It can cause sudden obsessive-compulsive behaviors. It can also
cause children to suddenly restricte their food intake. Researchers want to learn more about
children with PANS. They also want to learn more about the illness.
Objective:
To study some disorders of behavior and emotion that start in childhood.
Eligibility:
Children 3 14 years old who have had severe obsessive-compulsive symptoms or food restriction
start quickly
Design:
Parents will answer questions. The topics include:
Their child s medical history
Their child s physical and mental health
Their family history. The focus will be on neurodevelopmental and psychiatric conditions. A
family tree will be drawn.
Participants will have a physical exam.
Participants may take tests on paper or computer. These will focus on thinking, memory, and
behavior.
Participants and parents will give a blood sample.
Participants will have magnetic resonance imaging (MRI). A strong magnetic field and radio
waves take pictures of the brain. Participants will lie on a table that slides in and out of
a metal scanner.
Participants may have photos or videos taken.
Participants may have other tests. These may include heart tests, sleep tests, and lumbar
puncture.
Sponsoring Institute: National Institute of Mental Health
This multi-site study is intended to collect data and samples from a nationwide cohort of
children with Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). PANS is defined by
three clinical criteria:
1. Abrupt, dramatic onset of obsessive-compulsive disorder (OCD) or severely restricted
food intake AND
2. Concurrent presence of additional neuropsychiatric symptoms, with similarly severe and
acute onset, from at least two of the following seven categories:
- Anxiety (particularly separation anxiety)
- Emotional lability and depression
- Irritability, aggression, and/or severely oppositional behaviors
- Behavioral (developmental) regression
- Deterioration in school performance (due to inattention, concentration
difficulties, memory deficits, or others)
- Sensory or motor abnormalities
- Somatic signs and symptoms, including sleep disturbances, enuresis, or urinary
frequency
3. Symptoms are not better explained by a known neurologic or medical disorder, such as
Sydenham chorea, systemic lupus erythematosus, Tourette disorder, or others.
As a clinical syndrome, PANS likely represents a number of different disorders with unique
symptom constellations, disease mechanisms, and etiologies. The purpose of this investigation
is to identify these distinctive disorders by carefully documenting, archiving, and analyzing
the clinical features of each case of PANS, including not only details of the onset and
course of symptoms, but also results of physical examination, laboratory assays, and
paraclinical assessments, such as electroencephalography (EEG), polysomnography (PSG), brain
imaging (e.g., magnetic resonance imaging [MRI] scans), and others. In addition to defining
the unique clinical features associated with a specific disorder, we also hope to identify
biomarkers of risk and disease severity, including not only determinant genes, but also
environmental triggers, such as those producing post-infectious autoimmunity (e.g., Pediatric
Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection, or PANDAS). To
accomplish this, we propose to collect and archive clinical information and biospecimens at
different stages of the illness (e.g., initial onset, first exacerbation, following known
environmental triggers, during convalescence, etc.) and also to compare these results against
data and specimens obtained from healthy controls and children with non-PANDAS OCD, tics,
anxiety disorders, or eating disorder. Clinical, laboratory, and biomedical data will be
stored in the NIMH database (housed on the Clinical Trials Database [CTDB] of NICHD) and
blood, genetic material, and other biospecimens, including microbial cultures, stored in the
NIMH Genetics/Biological Repository. There are two types of baseline evaluations within this
protocol. The first is limited to participants with acute-onset neuropsychiatric symptoms
(PANS subjects) and will be conducted in the NIH Clinical Center by investigators from the
NIMH Section on Behavioral Pediatrics (Drs. Swedo, Grant, and Hommer.) These in-depth
phenotyping evaluations will include medical and psychiatric history, family history,
completion of standardized questionnaires, physical and neurological examinations,
neuropsychological testing, MRI scan, throat swab (for microbiologic testing), cheek swab (to
obtain genetic samples), and phlebotomy to obtain blood for laboratory assays and genetic
testing. Children with undiagnosed acute-onset neuropsychiatric symptoms may undergo
additional testing as part of the diagnostic evaluation; these assessments might include
(among others), electroencephalography (EEG), echocardiogram/electrocardiogram (ECHO/ECG)
and/or polysomnography (PSG). If the child s clinical presentation warrants a lumbar puncture
as part of the diagnostic evaluation, (e.g. abnormal findings on neurologic exam, EEG or PSG,
or lab abnormalities suggestive of systemic autoimmunity or neuroinflammation), a sample of
cerebrospinal fluid will be collected for research, as well as for clinical testing. Sedation
will not be used for these lumbar punctures, nor will it be used for any research purposes in
this protocol.
The second type of baseline evaluation will be used at NIMH for subjects with non-PANDAS
psychiatric disorders and healthy volunteers. At participating extramural institutions, this
is the evaluation that will be used for all participants (PANS, non-PANS, healthy volunteers)
evaluated. These evaluations will include standardized questionnaires, medical and
psychiatric history, family history, physical examination, throat swab (for microbiologic
testing), cheek swab (to obtain genetic samples), and phlebotomy to obtain blood for clinical
assays and research, including genetic studies. The assessments will generally be completed
in an outpatient clinic at the participating site, but also might be performed on
hospitalized children, if their medical condition permits research participation. Family
members of PANS probands will have a medical and psychiatric history and physical exam and
provide a blood sample (or cheek swab) for genetic research.
The Affected Probands, Healthy Volunteers, and Subjects with Non-PANS Psychiatric Disorders
will have follow-up evaluations annually, as well as on Ad Hoc basis. The Annual check-ups
will include an interim clinical history and relevant symptom ratings (tailored to the
subject s clinical profile). These follow-up evaluations may be done by phone or
videoconference. Ad hoc evaluations will occur during periods of health (if not healthy at
baseline) and during an episode of acute illness (either infectious illness or
neuropsychiatric symptom exacerbations) and convalescence (at least 8 weeks after recovery).
These in-person evaluations will include an interim clinical history, relevant symptom
ratings, phlebotomy to obtain research bloods, and in some cases, acquisition of microbial
samples (oral, nasal, nasopharyngeal and/or pharyngeal swabs, and feces). To identify
biomarkers of disease and recovery, children with PANS may be followed until their 18th
birthday, even if fully recovered from their acute illness. Healthy volunteers and
psychiatric controls will be followed no longer than 3 years from study entry.
This is a natural history study, with the primary goal of collecting clinical data and
biospecimens in order to identify subgroups of patients sharing a common disease mechanism
and thus provide opportunities for development of new treatment and prevention strategies.
The wealth of clinical information and the large number of biologic and genetic samples
acquired in this prospective, longitudinal investigation also permits us to address four
specific aims:
1. Identify unique and distinctive clinical, paraclinical, and laboratory features of
acuteonset neuropsychiatric disorders among patients meeting criteria for PANS.
2. Determine the role of environmental pathogens, such as Group A streptococci, in the
etiopathogenesis of acute-onset neuropsychiatric disorders.
3. Investigate factors influencing host susceptibility and resistance.
4. Elucidate the role of immune dysfunction in PANS or a subgroup of its patients.
5. Provide clinical diagnostic assessments to children with undiagnosed acute-onset
neuropsychiatric symptoms.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02190292 -
PANS - A Detailed Study of the Patients, Their Symptoms, Biomarkers and Treatment Offered in a Scandinavian Cohort
|