Late Onset SchizophreniaNCT06336382
Tau Biomarkers in Late-onset Psychosis (LOP)
An observational study of Late Onset Schizophrenia and Delusional Disorder (Late Onset), run by Jeremy Koppel at 1 site in United States.
Trial summary
Hallucinations or delusions that occur for the first time in older people with no acute medical problems or mood symptoms may be related to impending dementia. This study aims to confirm this hypothesis using novel blood biomarkers and Positron Emission Tomography (PET) imaging tracers, as well as non-invasive testing. Read more about this study
- Who is it for?
- Ages 65 to 85 years
- Conditions the study is for
- Late Onset Schizophrenia, Delusional Disorder (Late Onset)
- What is being tested?
- Tau PET imaging scan
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Feb 2024to 30 Jun 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 65 to 85 years
- All sexes
- Older adult
Study population: Very late-onset schizophrenia-like psychosis (VLSOP) diagnostic criteria: VLSOP is a schizophrenia-like condition characterized by the onset of delusions (primarily persecutory but also bizarre delusions) and/or hallucinations (auditory, visual, tactile, or olfactory) after age 60 in the absence of negative symptoms, formal thought disorder, and affective flattening that are common in early-onset schizophrenia. Delusional disorder diagnostic criteria: Delusional disorder comprises the presences of non-bizarre delusions including erotomanic, grandiose, jealous, persecutory, or somatic subtypes. The presence of one (or more) above delusions with a duration of 1 month or longer.
Who may be able to join
- Male or female, aged 65-85 years.
- Diagnosis of late-onset non-affective primary psychotic disorder consistent with either very late-onset schizophrenia-like psychosis (VLOSP, International Late-Onset Schizophrenia Group consensus criteria, Howard et al., 2000) or delusional disorder (DSM-5 criteria)
- Caregiver available to provide collateral history and participation in informant-based ratings (NPI,CDR)
- Clinical Dementia Rating (CDR) score of 0 or 0.5.
- Mini-Mental State Examination (MMSE) score ≥ 24 and at the screening visit.
- Normal memory function (to rule-out mild cognitive impairment, MCI) documented by scoring within 1.5 SD range in education adjusted norms of the Logical Memory II subscale
- Ability to hear 500, 1000 and 1500 Hz bilaterally on a hearing evaluation (hearing aids permitted).
Who cannot join
- Participants with affective and psychotic disorders including bipolar disorder, schizoaffective disorder, active major depression; insulin dependent type 2 diabetes; a history of CVD; a history of epilepsy; a history of TBI with greater than 15 minutes of loss of consciousness; a movement disorder including Parkinson's disease; stroke; autoimmune disease affecting the CNS; substance abuse disorder; or active delirium/encephalopathy.
- Evidence of a clinically relevant neurological disorder
- Modified Hachinski ischemia score of more than 4.
- History of alcoholism or drug dependency/abuse within the last 5 years before screening.
- Presence of metal implants such as pacemakers, ear implants, internal bullet fragments or shrapnel.
- Inability to lie flat for 1 hour approximately.
- Hearing impairment as evidenced by the inability to hear 500, 1000 and 1500 Hz bilaterally on a hearing evaluation. Subjects with hearing aids will be allowed to participate if they meet minimum hearing requirements.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
The Feinstein Institutes for Medical Research
Manhasset, New York, 11030
Erica Christen, MS, 516-562-3492, EChriste@northwell.edu
Michelle Gong, AS, 516-562-3492, MGong@northwell.edu
About this study
Hallucinations or delusions that occur for the first time in older people with no acute medical problems or mood symptoms may be related to impending dementia. This study aims to confirm this hypothesis using novel blood biomarkers and Positron Emission Tomography (PET) imaging tracers, as well as non-invasive testing.
Read the detailed description
Psychotic symptoms that occur in advanced age in the absence of an acute medical condition or prominent mood symptoms can represent the late appearance of primary psychotic disorders such as very late-onset schizophrenia-like psychosis (VLOSP) or delusional disorder, or can presage the appearance of a neurodegenerative condition such as Alzheimer's disease (AD). An episode of non-affective psychosis late in life more than doubles the risk of subsequent neurodegenerative disease, with an average time from psychosis to AD diagnosis of 18 months. The biologic mechanisms responsible for the increased risk of dementia in those who experience psychosis are unclear. One hypothesis is reverse causality, in which inchoate neurodegeneration is responsible for psychotic symptoms that emerge in the absence of traditional cognitive hallmarks of dementia. The psychosis then heralds the inception of illness that will eventuate in cognitive decline. The investigators will utilize neurodegenerative biomarkers in the form of novel PET imaging tracers, plasma immunoassays and non-invasive neurophysiologic measurements to test this hypothesis in a pilot cohort of elderly subjects suffering with psychosis occurring in late-life without dementia for comparison with a cohort of healthy elderly controls (HEC)s who are participating in a study focused on those with dementia.
- Being tested
- Tau PET imaging scan
- Medical subject headings
- Schizophrenia, Paranoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tau PET imaging scanDiagnostic test
Also called Tau PET scan
Subjects will be scanned with novel tau PET tracer [18F] PI-2620 to determine whether neurofibrillary tangle pathology is present.
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantification of neurofibrillary tangle pathology in subjects via PET [18F]PI-2620 radiotracer uptake.
To determine whether there are increases in tau pathology in those with psychotic episodes that occur late in life employing tau PET ligands, and whether those increases are etiologic contributors to a stable psychosis or are a presage of an incipient cognitive decline.
Measured: Each subject will have one PET imaging scan at visit 3 (week 4).
Secondary outcomes (1)
Measurement of peripheral soluble tau pathology with tau plasma immunoassays.
Plasma samples will be collected via venipuncture from LOP subjects and batch shipped to Quanterix Inc. for ptau analyses and quantification on the SiMOA SR-X analyzer platform.
Measured: Each subject will have blood collected at visit 1 or 2 (week 1 or 2).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2024
- Study start16 Feb 2024
- Primary completion31 Dec 2026 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Late Onset SchizophreniaStudies 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
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jeremy Koppel
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor-investigator, Jeremy Koppel, Northwell Health
- Investigators
- Jeremy Koppel, MD, Principal investigator, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06336382
- Sponsor's protocol ID
- 23-0874
- Other IDs
- 1R21MH135148
- Status last verified
- Nov 2026
- First submitted
- 20 Mar 2024
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Raw imaging files and neurocognitive data will be made available to other researchers via the NIMH Data Repository. Demographic data including age, sex, ethnicity and diagnosis will be shared. Information needed to generate a global unique identifier for the NIMH Data Archive (NDA) will be collected for each subject. In addition to the subject level data described above, all PET and MRI designs and experiment definitions, and study protocols will be deposited in the NDA.
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tau Biomarkers in Late-onset Psychosis (LOP)
- ClinicalTrials.gov ID
- NCT06336382
- Acronym / sponsor ID
- 23-0874
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Jeremy KoppelUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 16 Feb 2024 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 28 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hallucinations or delusions that occur for the first time in older people with no acute medical problems or mood symptoms may be related to impending dementia. This study aims to confirm this hypothesis using novel blood biomarkers and Positron Emission Tomography (PET) imaging tracers, as well as non-invasive testing.
Detailed description
Psychotic symptoms that occur in advanced age in the absence of an acute medical condition or prominent mood symptoms can represent the late appearance of primary psychotic disorders such as very late-onset schizophrenia-like psychosis (VLOSP) or delusional disorder, or can presage the appearance of a neurodegenerative condition such as Alzheimer's disease (AD). An episode of non-affective psychosis late in life more than doubles the risk of subsequent neurodegenerative disease, with an average time from psychosis to AD diagnosis of 18 months. The biologic mechanisms responsible for the increased risk of dementia in those who experience psychosis are unclear. One hypothesis is reverse causality, in which inchoate neurodegeneration is responsible for psychotic symptoms that emerge in the absence of traditional cognitive hallmarks of dementia. The psychosis then heralds the inception of illness that will eventuate in cognitive decline. The investigators will utilize neurodegenerative biomarkers in the form of novel PET imaging tracers, plasma immunoassays and non-invasive neurophysiologic measurements to test this hypothesis in a pilot cohort of elderly subjects suffering with psychosis occurring in late-life without dementia for comparison with a cohort of healthy elderly controls (HEC)s who are participating in a study focused on those with dementia.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 65 to 85 years
- Sex
- All
- Age groups
- Older adult
- Study population
- Very late-onset schizophrenia-like psychosis (VLSOP) diagnostic criteria: VLSOP is a schizophrenia-like condition characterized by the onset of delusions (primarily persecutory but also bizarre delusions) and/or hallucinations (auditory, visual, tactile, or olfactory) after age 60 in the absence of negative symptoms, formal thought disorder, and affective flattening that are common in early-onset schizophrenia. Delusional disorder diagnostic criteria: Delusional disorder comprises the presences of non-bizarre delusions including erotomanic, grandiose, jealous, persecutory, or somatic subtypes. The presence of one (or more) above delusions with a duration of 1 month or longer.
Key inclusion criteria (7 listed)
- Male or female, aged 65-85 years.
- Diagnosis of late-onset non-affective primary psychotic disorder consistent with either very late-onset schizophrenia-like psychosis (VLOSP, International Late-Onset Schizophrenia Group consensus criteria, Howard et al., 2000) or delusional disorder (DSM-5 criteria)
- Caregiver available to provide collateral history and participation in informant-based ratings (NPI,CDR)
- Clinical Dementia Rating (CDR) score of 0 or 0.5.
- Mini-Mental State Examination (MMSE) score ≥ 24 and at the screening visit.
Key exclusion criteria (7 listed)
- Participants with affective and psychotic disorders including bipolar disorder, schizoaffective disorder, active major depression; insulin dependent type 2 diabetes; a history of CVD; a history of epilepsy; a history of TBI with greater than 15 minutes of loss of consciousness; a movement disorder including Parkinson's disease; stroke; autoimmune disease affecting the CNS; substance abuse disorder; or active delirium/encephalopathy.
- Evidence of a clinically relevant neurological disorder
- Modified Hachinski ischemia score of more than 4.
- History of alcoholism or drug dependency/abuse within the last 5 years before screening.
- Presence of metal implants such as pacemakers, ear implants, internal bullet fragments or shrapnel.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tau PET imaging scanAlso: Tau PET scanSubjects will be scanned with novel tau PET tracer [18F] PI-2620 to determine whether neurofibrillary tangle pathology is present. | Diagnostic test | – |
Primary outcome
Quantification of neurofibrillary tangle pathology in subjects via PET [18F]PI-2620 radiotracer uptake.
Time frame: Each subject will have one PET imaging scan at visit 3 (week 4).
To determine whether there are increases in tau pathology in those with psychotic episodes that occur late in life employing tau PET ligands, and whether those increases are etiologic contributors to a stable psychosis or are a presage of an incipient cognitive decline.
1 secondary outcome
Measurement of peripheral soluble tau pathology with tau plasma immunoassays.
Time frame: Each subject will have blood collected at visit 1 or 2 (week 1 or 2).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Individual participant dataSharing planned: Yes. Raw imaging files and neurocognitive data will be made available to other researchers via the NIMH Data Repository. Demographic data including age, sex, ethnicity and diagnosis will be shared. Information needed to generate a global unique identifier for the NIMH Data Archive (NDA) will be collected for each subject. In addition to the subject level data described above, all PET and MRI designs and experiment definitions, and study protocols will be deposited in the NDA.
Related trials for Late Onset Schizophrenia
Recruiting
Ultra-High Resolution PET in Aging, Neurodegeneration and Psychotic Disorders
Alzheimer Dementia (AD), ALS - Amyotrophic Lateral Sclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jeremy Koppel, MD principal investigator
Northwell Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Late Onset Schizophrenia and Delusional Disorder (Late Onset), run by Jeremy Koppel at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nichole Hoehn, MS (516-562-3492, nhoehn@northwell.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quantification of neurofibrillary tangle pathology in subjects via PET [18F]PI-2620 radiotracer uptake. (time frame: Each subject will have one PET imaging scan at visit 3 (week 4).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.