Neuropsychiatric DisordersNCT07877246
A Longitudinal Natural History Study of Immune Biomarkers in Neuropsychiatric Illness
An observational study of Neuropsychiatric Disorders and Neuroinflammatory Disorders, run by National Institute of Mental Health (NIMH) at 3 sites in United States.
Trial summary
Background: Some brain or mental health conditions may be caused when a person s immune system attacks their own body. These are called immunologic neuropsychiatric disorders. In this natural history study, researchers want to see if they can find substances in the blood that can help them identify people with this… Read more about this study
- Who is it for?
- Ages 1 month to 100 years
- Conditions the study is for
- Neuropsychiatric Disorders, Neuroinflammatory Disorders, Post-Infectious Neuropsychiatric Disorders
- How many people
- 5,000 participants
- Where
- 3 sitesUnited States
- Study dates
- 19 Oct 2026to 30 Sep 2036
- Phase
- Observational
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 1 month to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The study population includes individuals with neuropsychiatric illnesses of possible neuroinflammatory or post-infectious etiology who meet the protocol eligibility criteria. Participants may provide prospectively collected blood biospecimens and associated clinical information, including medical and psychiatric history, neuropsychiatric symptoms, infection history, prior diagnostic testing, and other relevant clinical features. The study may also include existing biospecimens obtained from external sources or repositories, including control biospecimens.
Who may be able to join
- At the time of enrollment:
- Participants must be 1 month or above in age.
- Participant biospecimens must be physically located in the United States, or its territories or freely associated states
- Participants must have a neuropsychiatric illness of possible neuroinflammatory, or post-infectious etiology based on clinical report and findings from the referring facility/provider.
- To include one or more of the following:
- known or suspected infection or inflammation of the nervous system,
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- new-onset post-infectious neuropsychiatric symptoms,
- new or recurrent neuropsychiatric symptoms in the setting of a diagnosed autoimmune disease or proinflammatory disease state (e.g. systemic lupus erythematosus, sarcoidosis, Sjogren s, Down Syndrome),
- new-onset neuropsychiatric symptoms within 5 years of a cancer diagnosis,
- new-onset neuropsychiatric symptoms in the context of immune checkpoint inhibitor therapy,
- new-onset neuropsychiatric symptoms in the setting of a known or clinically supported primary immune deficiency,
- subacute onset psychiatric symptoms with cognitive impairment or personality change defined as a progression from baseline to functionally impaired within 3 months of the onset of symptoms,
- or have a typical psychiatric presentation with neuroimaging, CSF, or laboratory findings suggestive of neuroinflammatory process
- At the time of enrollment participants or surrogates will:
- be willing to participate in the protocol s procedures, unless clinically contraindicated,
- provide informed consent, either directly or via an appointed legally authorized representative,
- be willing to consent to secondary use of clinical data and biological samples collected at and prior to the time of their enrollment
Who cannot join
- Participant currently under involuntary commitment/hold.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
- Recruiting
Childrens Hospital, Los Angeles
Los Angeles, California, 90054-0700
About this study
Background:
Some brain or mental health conditions may be caused when a person s immune system attacks their own body. These are called immunologic neuropsychiatric disorders. In this natural history study, researchers want to see if they can find substances in the blood that can help them identify people with this kind of brain or mental illness. What they learn may help them find better ways to diagnose and treat these conditions in the future.
Read more
Objective:
To collect blood samples from people with a brain or mental illness that may be related to their immune system.
Eligibility:
People ages 1 month or older with a brain or mental illness that may be related to their immune system.
Design:
Participants will have 1 visit. This visit may be in person or by telehealth. They will answer a questionnaire about their health. They may have blood drawn for testing; this blood sample may also be taken at another medical facility and sent to the researchers.
Researchers will look at the participant s medical records and images over time. Researchers will also collect leftover blood or other tissue samples that are taken in the course of a participant s routine health care.
Participants may opt to have more visits. These visits will be every 3 to 12 months for up to 5 years. They will be asked about changes in their health since their last visit. They may opt to have blood drawn for research.
Read the detailed description
Study Description:
This study aims to identify and characterize biomarkers in biospecimens collected during clinical care or research encounters, which are not required for clinical or research testing. These "surplus" biospecimens consist of: (1) residual tissue, blood, or CSF remaining after clinical testing is complete; (2) additional blood collected for research purposes at the time of clinical biospecimen collection; (3) residual tissue, blood or CSF collected as part of a human research study; or (4) additional blood collected solely for this research protocol at the same time as biospecimen collection for a separate research protocol from which research blood are already being collected. Additionally, (5) blood will be collected longitudinally from a subset of enrolled participants. Biospecimen categories 1 - 4 do not require an additional venipuncture, whereas 5 does require an additional venipuncture. The biospecimen collection events will occur: (1) at the National Institutes of Health (NIH), (2) at medical centers and academic research institutions, and (3) at commercial phlebotomy facilities in the United States and its affiliated territories. Research activities utilizing the collected biospecimens will occur (1) at the NIH or, after de-identification, in (2) collaborating research laboratories or (3) commercial service facilities. It is anticipated that such studies will yield molecular correlates of and biomarkers for diverse neuropsychiatric illnesses.
Objectives:
The primary objective of this study is to identify immune factors that improve the diagnosis and classification of individuals with suspected immune-associated neuropsychiatric disorders.
The secondary objective is to correlate these immune factors with endotypes and endophenotypes of diverse neuropsychiatric disorders.
Endpoints:
Primary Endpoints:
- Identification of autoantibodies that are recurrently detected and statistically enriched (presence vs absence) in prespecified neuropsychiatric diagnostic or phenotypic subgroups compared with control participants, using twosided Fisher's Exact tests, with adjustment for multiple comparisons as appropriate.
- Identification of biomarker signatures that reliably classify psychotic subgroups as distinct from controls.
Secondary Endpoints:
-Derivation and characterization, when feasible, of research grade human monoclonal autoantibodies from biospecimens of participants with candidate or recurrent autoantibody responses, for use in in vitro and ex vivo mechanistic studies.
- Conditions
- Neuropsychiatric Disorders, Neuroinflammatory Disorders, Post-Infectious Neuropsychiatric Disorders
- Keywords
- Neuropsychiatric Disorders, Neuroinflammation, Post-infectious neuropsychiatric disorders, Infection-associated neuropsychiatric disorders, Neuroimmune disorders, Immune-mediated neuropsychiatric disorders, Neuropsychiatric symptoms, Post-infectious neurological disorders, Biospecimens, Neuroimmune Biomarkers
- Medical subject headings
- Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Individuals with neuropsychiatric illness | Individuals with neuropsychiatric illnesses of possible neuroinflammatory or post-infectious etiology |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of Recurrent Autoantibodies in Neuropsychiatric Subgroups
Identification of autoantibodies that are recurrently detected and statistically enriched (presence versus absence) in prespecified neuropsychiatric diagnostic or phenotypic subgroups compared with control participants.
Measured: Through study completion, up to 10 years
Secondary outcomes (1)
Correlate these immune factors with endotypes and endophenotypes of diverse neuropsychiatric disorders.
Identification of biomarker signatures that reliably classify psychotic subgroups as distinct from controls.
Measured: Through study completion, up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2026
- Study start19 Oct 2026
- Primary completion17 Sep 2036 (estimated)
- Study completion30 Sep 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (35)Papers the sponsor has linked to this study.
- Other trials for Neuropsychiatric DisordersStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 5,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Christopher M Bartley, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07877246
- Sponsor's protocol ID
- 10002709
- Other IDs
- 002709-M
- Status last verified
- 15 Oct 2026
- First submitted
- 10 Oct 2026
- Last updated
- 22 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Endres D, Meixensberger S, Dersch R, Feige B, Stich O, Venhoff N, Matysik M, Maier SJ, Michel M, Runge K, Nickel K, Urbach H, Domschke K, Pruss H, Tebartz van Elst L. Cerebrospinal fluid, antineuronal autoantibody, EEG, and MRI findings from 992 patients with schizophreniform and affective psychosis. Transl Psychiatry. 2020 Aug 12;10(1):279. doi: 10.1038/s41398-020-00967-3.
PubMed 32782247Zalla PG. [A rare case of gastric subserous lymphagioendothelioma spreading into the small omentum and retrogastric site]. Arch De Vecchi Anat Patol. 1967 Jun;49(1):289-99. No abstract available. Italian.
PubMed 5606187Burbelo PD, Castagnoli R, Shimizu C, Delmonte OM, Dobbs K, Discepolo V, Lo Vecchio A, Guarino A, Licciardi F, Ramenghi U, Rey-Jurado E, Vial C, Marseglia GL, Licari A, Montagna D, Rossi C, Montealegre Sanchez GA, Barron K, Warner BM, Chiorini JA, Espinosa Y, Noguera L, Dropulic L, Truong M, Gerstbacher D, Mato S, Kanegaye J, Tremoulet AH; Pediatric Emergency Medicine Kawasaki Group; Eisenstein EM, Su HC, Imberti L, Poli MC, Burns JC, Notarangelo LD, Cohen JI. Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C. Front Immunol. 2022 Mar 11;13:841126. doi: 10.3389/fimmu.2022.841126. eCollection 2022.
PubMed 35360001Forcadela M, Rocchi C, San Martin D, Gibbons EL, Wells D, Woodhall MR, Waters PJ, Huda S, Hamid S. Timing of MOG-IgG Testing Is Key to 2023 MOGAD Diagnostic Criteria. Neurol Neuroimmunol Neuroinflamm. 2023 Nov 17;11(1):e200183. doi: 10.1212/NXI.0000000000200183. Print 2024 Jan.
PubMed 37977848de Beer F, Schreurs MW, Foncke EM. False positive autoantibodies to glutamic acid decarboxylase in opsoclonus-myoclonus-ataxia syndrome after intravenous treatment with immunoglobulin. Clin Neurol Neurosurg. 2009 Sep;111(7):643-4. doi: 10.1016/j.clineuro.2009.03.010. Epub 2009 May 12. No abstract available.
PubMed 19442432Washburn N, Meccariello R, Hu S, Hains M, Bhatnagar N, Sarvaiya H, Kapoor B, Schaeck J, Pino I, Manning A, Lansing JC, Bosques CJ. High-resolution physicochemical characterization of different intravenous immunoglobulin products. PLoS One. 2017 Jul 31;12(7):e0181251. doi: 10.1371/journal.pone.0181251. eCollection 2017.
PubMed 28759653Gruter T, Ott A, Meyer W, Jarius S, Kinner M, Motte J, Pitarokoili K, Gold R, Komorowski L, Ayzenberg I. Effects of IVIg treatment on autoantibody testing in neurological patients: marked reduction in sensitivity but reliable specificity. J Neurol. 2020 Mar;267(3):715-720. doi: 10.1007/s00415-019-09614-4. Epub 2019 Nov 14.
PubMed 31728710Singer HS. PANDAS: The Need to Use Definitive Diagnostic Criteria. Tremor Other Hyperkinet Mov (N Y). 2015 Jul 6;5:327. doi: 10.7916/D8PN94RQ. eCollection 2015.
PubMed 26196028Mandel-Brehm C, Benson LA, Tran B, Kung AF, Mann SA, Vazquez SE, Retallack H, Sample HA, Zorn KC, Khan LM, Kerr LM, McAlpine PL, Zhang L, McCarthy F, Elias JE, Katwa U, Astley CM, Tomko S, Dalmau J, Seeley WW, Pleasure SJ, Wilson MR, Gorman MP, DeRisi JL. ZSCAN1 Autoantibodies Are Associated with Pediatric Paraneoplastic ROHHAD. Ann Neurol. 2022 Aug;92(2):279-291. doi: 10.1002/ana.26380. Epub 2022 May 25.
PubMed 35466441Blinder T, Lewerenz J. Cerebrospinal Fluid Findings in Patients With Autoimmune Encephalitis-A Systematic Analysis. Front Neurol. 2019 Jul 25;10:804. doi: 10.3389/fneur.2019.00804. eCollection 2019.
PubMed 31404257Poore B, Hamilton R, Kelliher MT, Mahmood S, Mindiola-Romero AE, Richards R, Motanagh S, Cervinski MA, Nerenz RD. Retrospective Evaluation of the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) Score. J Appl Lab Med. 2022 Jan 5;7(1):36-45. doi: 10.1093/jalm/jfab106.
PubMed 34996088Panda PK, Ramachandran A, Sharawat IK, Tomar A, Elwadhi A, Kumar V, Bhat NK. Performance of a pediatric adaptation of the RITE2 and APE2 scores in children with autoimmune epilepsy: P-RITE2 and P-APE2 scores. Seizure. 2022 Dec;103:11-17. doi: 10.1016/j.seizure.2022.10.005. Epub 2022 Oct 4.
PubMed 36244182Rafferty T, Koeppen-Babcock A, Muppidi S, Li Y, Le S. Utilization of APE2 and RITE2 scores in autoimmune encephalitis patients with seizures. Epilepsy Behav. 2024 May;154:109737. doi: 10.1016/j.yebeh.2024.109737. Epub 2024 Mar 21.
PubMed 38518672Pruss H. Autoantibodies in neurological disease. Nat Rev Immunol. 2021 Dec;21(12):798-813. doi: 10.1038/s41577-021-00543-w. Epub 2021 May 11.
PubMed 33976421Deutscher S. Phage Display to Detect and Identify Autoantibodies in Disease. N Engl J Med. 2019 Jul 4;381(1):89-91. doi: 10.1056/NEJMcibr1903249. No abstract available.
PubMed 31269373