PANS Pediatric Acute-Onset Neuropsychiatric Syndrome
Conditions
Brief summary
Open-label prospective trial to study efficacy, safety and tolerability of intravenous immunoglobulin (IVIG) once monthly for 6 months in children and adolescents with PANS. Number of subjects: 10. Age range: 4-17 years. Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a recently defined research diagnosis describing an abrupt, dramatic onset of neuropsychiatric symptoms including obsessions/compulsions and/or food restriction in children. Immunologic mechanisms are suspected, but treatment trials are few.
Detailed description
Open-label prospective trial to study efficacy, safety and tolerability of intravenous immunoglobulin (IVIG) once monthly for 6 months in children and adolescents with PANS (including the subgroup PANDAS). Number of subjects: 10. Age range: 4-17 years. Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a recently defined research diagnosis describing an abrupt, dramatic onset of neuropsychiatric symptoms including obsessions/compulsions and/or food restriction in children. Immunologic mechanisms are suspected, but treatment trials are few. The primary objective of this study is to evaluate the efficacy of intravenous immunoglobulin (IVIG), 2 g/kg given every 4 weeks for 6 months, to patients with post-infectious PANS/PANDAS, in improving neuropsychiatric symptoms and impairment. The secondary objectives of this study are to evaluate changes from baseline to follow-up at 3 months, 6 months and 12 months in: * Obsessive Compulsive Disorder (OCD) symptoms * adaptive functioning * quality of life * cognitive functioning * for patients with baseline inflammation signs on cerebral Magnetic Resonance Imaging (MRI) to evaluate changes in these measures after IVIG therapy after 6 months. * number of days of work/school/daily activities missed per subject year due to PANS/PANDAS before and after IVIG therapy * parental care load, e.g. need for sick leave, before and after IVIG therapy * Immunoglobulin (IgG, IgM and IgA) levels at baseline, 3 months, 6 months and 12 months * sustainability of any improvement at 12 months after initiation of IVIG measured with the PANS scale, CGI-S and CGI-I To assess the safety and tolerability of high dose IVIG therapy * Clinical signs and symptoms (nausea, headache, local reactions) * ALAT * Hemoglobin, complete blood count including leucocyte differential Investigational product: Intravenous immunoglobulin IVIG (Privigen), 2 g/kg BW every 4th week for 6 months (= 6 infusions).
Interventions
DRUGPrivigen Injectable Product (Intravenous Immunoglobulin)
Privigen, 2 g/kg BW every 4th week for 6 months (= 6 infusions).
Sponsors
Göteborg University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label single-arm trial
Eligibility
Sex/Gender
ALL
Age
4 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. The subject and parents/caregivers have given written consent or assent to participate in the study. 2. Children and adolescents between the ages of 4 and 17 years at Baseline. 3. Documented and confirmed pre-existing diagnosis of post-infectious PANS/PANDAS 4. The subject has not been treated with IVIG previously or not been treated for the last 6 months 5. If the patient is on long-term antibiotic prophylaxis, this should be unchanged one month before baseline and during the trial. Throat culture for Group A Streptococcus (GAS) should be performed before study start and standard phenoxymethyl penicillin treatment given if positive culture. 6. Infections occurring during the trial should be treated according to standard clinical practice. 7. Treatment with COX-inhibitors or corticosteroids should be discontinued at least one month before baseline and during the trial. Two-three days treatment with corticosteroids during and after IVIG treatment is allowed to reduce IVIG side effects such as headache and nausea. 8. Any psychopharmacological treatment (e.g. SSRI, antipsychotics), if considered essential for the subject, should be kept at a stable and unchanged dose from one month before baseline and during the trial. If not considered essential, it should be discontinued at least one month before baseline. 9. The medical records for all subjects should be available to document diagnosis, previous infections and treatment. 10. For female participants, adequate contraception should be used, see
Exclusion criteria
. A negative pregnancy test can possibly be a requirement, specify requirement/type of pregnancy test. Contraceptive requirements may also apply to male participants.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) scale symptoms and impairment | 6 months | Investigator-rated scale measuring symptom severity and impairment in Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), score range 0-50, lower is better |
| Change in CGI-S | 6 months | CGI-S (Clinical Global Impression-Severity) measures global symptom severity, score range 1-7, lower is better |
| CGI-I | 6 months | CGI-I (Clinical Global Impression-Improvement) measures global improvement, score range 1-7, lower is better |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in CY-BOCS scale | 6 months | CY-BOCS scale measures Obsessive Compulsive Disorder (OCD) Symptoms, investigator-rated, score range 0-40, lower is better |
| Change on ABAS (Adaptive Behavior Assessment System) II scale | 6 months | Measures level of functioning in everyday life, parent- and teacher-rated, score range 40-160, higher is better |
| Change on Child Health Inventory (CHIP-CE) scale | 6 months | Measures quality of life, parent-rated, standardized T-score, mean 50, standard deviation 10, higher score is better |
| Change on 5-15 scale | 6 months | Measures neuropsychiatric symptoms, score range 1-543, lower is better |
| Change in neuromotor functioning | 6 months | Neuromotor examination by investigator |
| Change in cognitive function | 6 months | Working memory test from Wechsler scale, standardized scores age norms, mean 100, standard deviation 10, higher is better |
| Change in School-PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) Scale | 6 months | Short version of PANS-scale rated by teacher or school assistant, score range 0-50, lower is better |
| School absence | 6 months | Days absent from school past 3 months or since last visit |
| Parental care load | 6 months | Sick leave number of days |
| Change in laboratory assessments | 6 months | Inflammatory measures as specified in CRF, lower is better |
| Adverse events | 6 months | Parent/child report |
| Magnetic Resonance Imaging (MRI) | 6 months | In a subgroup who can tolerate MRI without general anaesthesia. Specially developed protocol for measuring inflammation signs |
Countries
Sweden
Contacts
PRINCIPAL_INVESTIGATORChristopher Gillberg, Professor
Gillberg Neuropsychiatry, Centre Sahlgrenska Academy
Outcome results
None listed