Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a research diagnosis given to patients who have an abrupt, dramatic onset of neuropsychiatric symptoms including obsessions/compulsions and/or food restriction, and several other neuropsychiatric symptoms.
Conditions
Interventions
Trade Name: Privigen
Pharmaceutical Form: Solution for injection/infusion
Sponsors
Gillberg Neuropsychiatry Centre
Eligibility
Sex/Gender
All
Inclusion criteria
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. 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. Are the trial subjects under 18? yes Number of subjects for this age range: 10 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Clinical evidence of any significant acute or chronic disease that, in the opinion of the Investigator, may interfere with successful completion of the trial or place the subject at undue medical risk. Spinal tap results are required before study start to rule out encephalitis (which would need to be treated according to encephalitis treatment guidelines). 2. The subject has had a known serious adverse reaction to immunoglobulin or any severe anaphylactic reaction to blood or any blood-derived product 3. Females of childbearing potential who are pregnant, have a positive pregnancy test at Baseline (human chorionic gonadotropin [HCG]-based assay), are breastfeeding, or unwilling to practice a highly effective method of contraception (oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device [IUD] or intrauterine system [IUS], condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence) throughout the study Note: True abstinence: When this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods], declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception.) 4. The subject has significant proteinuria (dipstick proteinuria = 3+, known urinary protein loss > 1 g/24 hours, or nephrotic syndrome), has a history of acute renal failure, has severe renal impairment (blood urea nitrogen [BUN] or creatinine more than 2.5 times the upper limit of normal [ULN]), and/or is on dialysis 5. The subject has Screening Visit values of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels exceeding 2.5 times the ULN for the expected normal range for the testing laboratory. 6. The subject has hemoglobin 1 mg of prednisone equivalent/kg/day for > 30 days. Note: Intermittent courses of corticosteroids of not more than 10 days would not exclude a subject. Inhaled or topical corticosteroids are allowed. 14. The subject has known substance or prescription drug abuse. 15. The subject has participated in another clinical
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: To evaluate the efficacy of intravenous immunoglobulin (IVIG), 2 g/kg given every 4 weeks for 6 months, to patients with post-infectous PANS including the subgroup PANDAS, in improving neuropsychiatric symptoms and impairment (PANS Scale), global functioning (CGI-S) and improvement (CGI-I) in an open-trial design with rigorous clinical monitoring of symptom profiles before, during and after treatment. ;Secondary Objective: To evaluate changes from baseline to follow-up at 1 month, 3 months, 6 months and 12 months oin OCD symptoms, adaptive functioning, quality of life, cognitive functioning, signs of inflammation in MRI and spinal fluid •To evaluate number of days of work/school/daily activities missed per subject year due to PANS/PANDAS before and after IVIG therapy •To evaluate parental care load, e.g. need for sick leave, before and after IVIG therapy measured by •To evaluate through 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 Safety objective •To assess the safety and tolerability of high dose IVIG therapy oClinical signs and symptoms (nausea, headache, local reactions) oLiver and kidney function tests, hemoglobin, complete blood count including leucocyte differential ;Primary end point(s): The primary efficacy variables are: ochanges in symptom severity and impairment on the investigator-rated Pediatric Acute Neuropsychiatric Symptom (PANS) scale (Swedo, Leckman et al.). Clinical response is defined as >30% reduction in symptoms and impairment, respectively. ochanges in global symptoms and functioning measured by CGI-S (Clinical Global Impression-Severity) and in global improvement measured by CGI-I (Clinical Global Impression-Improvement). Clinical response is defined as a score of 1-2 on CGI-S and CGI-I, respectively. ;Timepoint(s) of evaluation of this end point: Baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Changes in: • OCD symptoms measured with the CY-BOCS scale • Level of functioning in everyday life assessed by the ABAS II scale (rated by parent or other caregiver and from the responsible teacher/preschool teacher) • Quality of life assessment (CHIP-CE scale - Parent report, rated by parent or other caregiver. • Neuropsychiatric and neurodevelopmental symptoms assessed by the parent-rated 5-15 scale (Kadesjö et al 2004). • Motor/neurologic functioning (neurologic assessment of choreiform movements, balance (Rombergs test with extended arms), diadochokinesis, finger-nose tapping, eye movements, muscle tone, reflexes, figure copying, drawing, handwriting). • Cognitive functioning (auditory working memory subtest from WISC-V. Visual working memory. VMI (visual perception test). • School-PANS (short version of PANS-scale rated by teacher or school assistant; Murphy, personal communication) • Days absent from school during the study period (3 months stage 1, 12 months stage 2) compared to previous 3 months • Parental situation, e.g. sick leave, reduced working hours • Trough concentrations of total IgG, IgA, IgM and at 3 mo, 6 mo • AEs, suspected adverse drug reactions (suspected ADRs), serious AEs (SAEs), and discontinuations due to AEs and SAEs • Vital signs during clinic visits (temperature [T], respiratory rate [RR], heart rate [HR], systolic blood pressure [SBP] and diastolic blood pressure [DBP]). • Physical assessments: physical exams will be recorded as normal or abnormal, according to the physician’s judgment criteria, and findings will be recorded. • Laboratory assessments including chemistry, hematology, and urinalysis. • In a subgroup of participants who can tolerate Cerebral Magnetic Resonance Tomography (MRI) without general anesthesia, MRI will be done according to a specific protocol (Hadjikani, personal communication) ;Timepoint(s) of evaluation of this end point: Baseline, 3, 6 and 12 months | — |
Countries
Sweden
Contacts
Public ContactGNC
Gillberg Neuropsychiatry Centre
Outcome results
None listed