SchizophreniaNCT00001247
Inpatient Evaluation of Adults With Schizophrenia
An observational study of Schizophrenia, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
The purpose of this study is to understand the biologic basis of schizophrenia and to determine which symptoms are related to the illness itself and which are related to medications used to treat the illness. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Sirolimus
- How many people
- 648 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Sep 1989to not given
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Individuals with schizophrenia-spectrum illness from the community.
Who may be able to join
- Diagnosis of DSM-IV- or DSM5-defined schizophrenia spectrum disorder (including schizophrenia, schizoaffective disorder, or other specified/unspecified schizophrenia spectrum and other psychotic disorder/psychosis NOS).
- Subjects with other neuropsychiatric disorders may also be admitted and participate in the protocol if there is sufficient evidence to believe they have an underlying, undiagnosed DSM-IV-or DSM5-defined schizophrenia spectrum disorder.
Who cannot join
- -Currently treated with depot medications
- Because of the long half-life of depot medications such as paliperidone palmitate (Invega Sustenna), applicants to our program will be excluded if they are currently receiving depot medications monthly. However, applicants may decide to switch from depot to oral medications on their own, in conjunction with their personal physician, before coming to the program. This is not part of research and we do not participate in this decision. A sufficient washout period based on the particular long-acting injectable medication s elimination half-life will be required in order for prospective participants to be eligible. Subjects may complete the last 3 months of washout in the inpatient unit while being evaluated under the standard protocol.
- -Major medical illness.
- Research subjects identified as having major medical problems other than their primary neuropsychiatric disorder will be excluded from admission.
- Applicants judged to be unsuitable for medication free studies will also be excluded. Possible reasons for exclusion include prior history of dangerousness to self or others, particularly when off medication.
- Applicants who are pregnant are excluded from this study. Volunteers who are found to be pregnant after testing will be terminated from study and referred to an OB-GYN for follow up care.
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- Infection with syphilis, hepatitis, or HIV.
- History of any (excepting nicotine-related and cannabis-related) DSM5-defined moderate to severe substance use disorder (or DSM-IV-defined substance dependence).
- Cumulative lifetime history of any (excepting nicotine-related and cannabis-related) DSM5-defined mild substance use disorder (or any DSM-IV-defined substance abuse), either in excess of 5 years total or not in remission for at least 6 months.
- Lack of capacity to provide consent.
- Exclusion Criteria for Previously Enrolled Research Subjects
- No longer satisfying the above inclusion criteria or meeting any of the above exclusion criteria
- Inability to safely participate in planned research (e.g., development of acute suicidal behavior during prior research participation)
- Unlikely to provide sufficient additional research data
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Inpatient Evaluation of Neuropsychiatric Patients
The purpose of this study is to understand the biologic basis of schizophrenia and to determine which symptoms are related to the illness itself and which are related to medications used to treat the illness.
Schizophrenia and related psychoses are chronic brain disorders whose prognosis is often poor and whose pathophysiology remains obscure. Brain imaging technologies such s positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and magnetic resonance imaging (MRI) offer opportunities to study the pathophysiology of psychotic disorders by evaluating brain function. However, the use of anti-psychotic drugs may interfere with the results of such studies. In this study, psychotropic medication will be discontinued in patients for a short period of time to distinguish the effects of the illness on the brain without the interference of the medication's effects on the brain. Given that there is a risk that the patient's symptoms will increase, they are asked to stay on an inpatient unit where the NIMH clinical staff is available to help them 24 hours a day.
This study will be conducted in three phases. In Phase 1, participants will be admitted to the Clinical Center while continuing to take their medication and will undergo diagnostic interviews, physical and laboratory assessments, physiological monitoring, and neuropsychological testing. Behavioral ratings will also be performed and blood and urine samples will be collected. During Phase 2, participants will continue taking medications in a blinded fashion for 8 to 12 weeks. The active medications will be replaced with a placebo (an inactive pill) part of that time. PET, fMRI, and MRI scans will be used to monitor how the continuation or lack of medication affects the brain. Psychological tests will also be given to measure changes in cognition. In Phase 3, participants will have the opportunity for clinical stabilization.
Read the detailed description
Objectives:
Schizophrenia and related psychoses are chronic brain disorders whose prognosis is often poor and whose pathophysiology remains obscure. Neuroimaging technologies such as PET (positron emission tomography), fMRI (functional magnetic resonance imaging), DTI (diffusion tensor imaging) and MRSI (magnetic resonance spectroscopic imaging) offer opportunities to elucidate the pathophysiology by studying brain function in living research subjects. The use of these techniques to study psychotic disorders is severely limited, however, by a critical methodological confound: antipsychotic treatment. The purpose of this protocol is to admit research subjects with schizophrenia and other related disorders to the Clinical Center, carefully evaluate their neuropsychiatric status, and discontinue psychotropic medications for a brief period so research subjects can be studied without the confound of antipsychotic treatment.
Study Population:
700 participants
The study will include research subjects with schizophrenia.
Study Design:
There are several phases to this protocol. The first phase is the Screening Evaluation and Stabilization Phase and includes gathering historical data, structured diagnostic interviews, general physical and laboratory assessments, basic physiological monitoring, neuropsychological testing, limited collection of blood and urine samples, and serial behavioral ratings. In the second phase (Coded Medication Phase), research subjects will receive blinded compounds that will contain inactive placebo or active antipsychotic administered in a crossover fashion. Patients and unit clinical nursing staff evaluating and caring for the patient will be blind to arm status. Each arm normally lasts 4 to 6 weeks. The total duration of this phase is 8 to 12 weeks. During the Coded Medication Phase, research subjects are enrolled in a series of neuroimaging and other approved studies designed to elucidate the neurobiology of these disorders. These include studies using neuropsychological testing, MEG, PET, fMRI, DTI, and MRSI. The antipsychotic free period is essential to distinguish the effects of illness versus medication.
Outcome Measures:
Parameters under investigation include traits that are candidate phenotypes for genetic studies and state-dependent aspects of brain function. The combined use of many neuroimaging modalities will allow us to look at the functional relationship between a variety of brain abnormalities hypothesized to play a role in schizophrenia. These include hippocampal neurochemical abnormalities, deficits in prefrontal cortical activation, and dysregulation of subcortical dopamine in a single research subject.
- Conditions
- Schizophrenia
- Being tested
- Sirolimus
- Keywords
- Schizophrenia, Psychosis, Schizoaffective, Neuroimaging, Cognition, Schizoaffective Disorder
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Drug not used in study.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Individuals with schizophrenia-spectrum illness from the community. Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
To map the physiological fMRI BOLD response, the brain electrical activity through MEG response and the blood flow, presynaptic and post-synaptic dopaminergic function through PET studies during different cognitive tasks
To map the physiological fMRI BOLD response, the brain electrical activity through MEG response and the blood flow, presynaptic and post-synaptic dopaminergic function through PET studies during different cognitive tasks
Measured: ongoing
To explore the neuropsychological response in research subjects with schizophrenia under placebo conditions without the confounding effect of antipsychotics.
To explore the neuropsychological response in research subjects with schizophrenia under placebo conditions without the confounding effect of antipsychotics.
Measured: ongoing
Secondary outcomes (1)
PANSS data will be collected to determine changes or lack thereof in clinical status during the protocol.
PANSS data will be collected to determine changes or lack thereof in clinical status during the protocol.
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start15 Sep 1989
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- 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
- 648 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Daniel P Eisenberg, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001247
- Sponsor's protocol ID
- 890160
- Other IDs
- 89-M-0160
- Status last verified
- 27 Feb 2026
- First submitted
- 3 Nov 1999
- Last updated
- 16 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Because a large share of the accrued dataset precludes broad sharing language in the consent, it is unlikely that sharing of only some IPD that underlie results in any given publication would be of scientific value.
Publications
Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE, Goldman D, Weinberger DR. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6917-22. doi: 10.1073/pnas.111134598. Epub 2001 May 29.
PubMed 11381111Meyer-Lindenberg A, Miletich RS, Kohn PD, Esposito G, Carson RE, Quarantelli M, Weinberger DR, Berman KF. Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia. Nat Neurosci. 2002 Mar;5(3):267-71. doi: 10.1038/nn804.
PubMed 11865311Rubinstein DY, Eisenberg DP, Carver FW, Holroyd T, Apud JA, Coppola R, Berman KF. Spatiotemporal Alterations in Working Memory-Related Beta Band Neuromagnetic Activity of Patients With Schizophrenia On and Off Antipsychotic Medication: Investigation With MEG. Schizophr Bull. 2023 May 3;49(3):669-678. doi: 10.1093/schbul/sbac178.
PubMed 36772948Eisenberg DP, Kohn PD, Hegarty CE, Smith NR, Grogans SE, Czarapata JB, Gregory MD, Apud JA, Berman KF. Clinical correlation but no elevation of striatal dopamine synthesis capacity in two independent cohorts of medication-free individuals with schizophrenia. Mol Psychiatry. 2022 Feb;27(2):1241-1247. doi: 10.1038/s41380-021-01337-1. Epub 2021 Nov 17.
PubMed 34789848
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inpatient Evaluation of Neuropsychiatric Patients
- ClinicalTrials.gov ID
- NCT00001247
- Acronym / sponsor ID
- 890160
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, Psychosis, Schizoaffective, Neuroimaging, Cognition, Schizoaffective Disorder
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 648 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 15 Sep 1989 (actual)
- First posted
- 4 Nov 1999 (estimated)
- 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.
The purpose of this study is to understand the biologic basis of schizophrenia and to determine which symptoms are related to the illness itself and which are related to medications used to treat the illness.
Schizophrenia and related psychoses are chronic brain disorders whose prognosis is often poor and whose pathophysiology remains obscure. Brain imaging technologies such s positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and magnetic resonance imaging (MRI) offer opportunities to study the pathophysiology of psychotic disorders by evaluating brain function. However, the use of anti-psychotic drugs may interfere with the results of such studies. In this study, psychotropic medication will be discontinued in patients for a short period of time to distinguish the effects of the illness on the brain without the interference of the medication's effects on the brain. Given that there is a risk that the patient's symptoms will increase, they are asked to stay on an inpatient unit where the NIMH clinical staff is available to help them 24 hours a day.
This study will be conducted in three phases. In Phase 1, participants will be admitted to the Clinical Center while continuing to take their medication and will undergo diagnostic interviews, physical and laboratory assessments, physiological monitoring, and neuropsychological testing. Behavioral ratings will also be performed and blood and urine samples will be collected. During Phase 2, participants will continue taking medications in a blinded fashion for 8 to 12 weeks. The active medications will be replaced with a placebo (an inactive pill) part of that time. PET, fMRI, and MRI scans will be used to monitor how the continuation or lack of medication affects the brain. Psychological tests will also be given to measure changes in cognition. In Phase 3, participants will have the opportunity for clinical stabilization.
Detailed description
Objectives:
Schizophrenia and related psychoses are chronic brain disorders whose prognosis is often poor and whose pathophysiology remains obscure. Neuroimaging technologies such as PET (positron emission tomography), fMRI (functional magnetic resonance imaging), DTI (diffusion tensor imaging) and MRSI (magnetic resonance spectroscopic imaging) offer opportunities to elucidate the pathophysiology by studying brain function in living research subjects. The use of these techniques to study psychotic disorders is severely limited, however, by a critical methodological confound: antipsychotic treatment. The purpose of this protocol is to admit research subjects with schizophrenia and other related disorders to the Clinical Center, carefully evaluate their neuropsychiatric status, and discontinue psychotropic medications for a brief period so research subjects can be studied without the confound of antipsychotic treatment.
Study Population:
700 participants
The study will include research subjects with schizophrenia.
Study Design:
There are several phases to this protocol. The first phase is the Screening Evaluation and Stabilization Phase and includes gathering historical data, structured diagnostic interviews, general physical and laboratory assessments, basic physiological monitoring, neuropsychological testing, limited collection of blood and urine samples, and serial behavioral ratings. In the second phase (Coded Medication Phase), research subjects will receive blinded compounds that will contain inactive placebo or active antipsychotic administered in a crossover fashion. Patients and unit clinical nursing staff evaluating and caring for the patient will be blind to arm status. Each arm normally lasts 4 to 6 weeks. The total duration of this phase is 8 to 12 weeks. During the Coded Medication Phase, research subjects are enrolled in a series of neuroimaging and other approved studies designed to elucidate the neurobiology of these disorders. These include studies using neuropsychological testing, MEG, PET, fMRI, DTI, and MRSI. The antipsychotic free period is essential to distinguish the effects of illness versus medication.
Outcome Measures:
Parameters under investigation include traits that are candidate phenotypes for genetic studies and state-dependent aspects of brain function. The combined use of many neuroimaging modalities will allow us to look at the functional relationship between a variety of brain abnormalities hypothesized to play a role in schizophrenia. These include hippocampal neurochemical abnormalities, deficits in prefrontal cortical activation, and dysregulation of subcortical dopamine in a single research subject.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | Drug: SirolimusIndividuals with schizophrenia-spectrum illness from the community. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals with schizophrenia-spectrum illness from the community.
Key inclusion criteria (2 listed)
- Diagnosis of DSM-IV- or DSM5-defined schizophrenia spectrum disorder (including schizophrenia, schizoaffective disorder, or other specified/unspecified schizophrenia spectrum and other psychotic disorder/psychosis NOS).
- Subjects with other neuropsychiatric disorders may also be admitted and participate in the protocol if there is sufficient evidence to believe they have an underlying, undiagnosed DSM-IV-or DSM5-defined schizophrenia spectrum disorder.
Key exclusion criteria (14 listed)
- -Currently treated with depot medications
- Because of the long half-life of depot medications such as paliperidone palmitate (Invega Sustenna), applicants to our program will be excluded if they are currently receiving depot medications monthly. However, applicants may decide to switch from depot to oral medications on their own, in conjunction with their personal physician, before coming to the program. This is not part of research and we do not participate in this decision. A sufficient washout period based on the particular long-acting injectable medication s elimination half-life will be required in order for prospective participants to be eligible. Subjects may complete the last 3 months of washout in the inpatient unit while being evaluated under the standard protocol.
- -Major medical illness.
- Research subjects identified as having major medical problems other than their primary neuropsychiatric disorder will be excluded from admission.
- Applicants judged to be unsuitable for medication free studies will also be excluded. Possible reasons for exclusion include prior history of dangerousness to self or others, particularly when off medication.
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 |
|---|---|---|
| SirolimusDrug not used in study. | Drug | 1 |
Primary outcome
To map the physiological fMRI BOLD response, the brain electrical activity through MEG response and the blood flow, presynaptic and post-synaptic dopaminergic function through PET studies during different cognitive tasks
Time frame: ongoing
To map the physiological fMRI BOLD response, the brain electrical activity through MEG response and the blood flow, presynaptic and post-synaptic dopaminergic function through PET studies during different cognitive tasks
To explore the neuropsychological response in research subjects with schizophrenia under placebo conditions without the confounding effect of antipsychotics.
Time frame: ongoing
To explore the neuropsychological response in research subjects with schizophrenia under placebo conditions without the confounding effect of antipsychotics.
1 secondary outcome
PANSS data will be collected to determine changes or lack thereof in clinical status during the protocol.
Time frame: Ongoing
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2026.
- Background: PubMed 11381111Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE, Goldman D, Weinberger DR. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6917-22. doi: 10.1073/pnas.111134598. Epub 2001 May 29.
- Background: PubMed 11865311Meyer-Lindenberg A, Miletich RS, Kohn PD, Esposito G, Carson RE, Quarantelli M, Weinberger DR, Berman KF. Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia. Nat Neurosci. 2002 Mar;5(3):267-71. doi: 10.1038/nn804.
- Derived from this study: PubMed 36772948Rubinstein DY, Eisenberg DP, Carver FW, Holroyd T, Apud JA, Coppola R, Berman KF. Spatiotemporal Alterations in Working Memory-Related Beta Band Neuromagnetic Activity of Patients With Schizophrenia On and Off Antipsychotic Medication: Investigation With MEG. Schizophr Bull. 2023 May 3;49(3):669-678. doi: 10.1093/schbul/sbac178.
- Derived from this study: PubMed 34789848Eisenberg DP, Kohn PD, Hegarty CE, Smith NR, Grogans SE, Czarapata JB, Gregory MD, Apud JA, Berman KF. Clinical correlation but no elevation of striatal dopamine synthesis capacity in two independent cohorts of medication-free individuals with schizophrenia. Mol Psychiatry. 2022 Feb;27(2):1241-1247. doi: 10.1038/s41380-021-01337-1. Epub 2021 Nov 17.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. Because a large share of the accrued dataset precludes broad sharing language in the consent, it is unlikely that sharing of only some IPD that underlie results in any given publication would be of scientific value.
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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. This study is not recruiting at the moment.
Daniel P Eisenberg, M.D. principal investigator
National Institute of Mental Health (NIMH)
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 Schizophrenia, run by National Institute of Mental Health (NIMH) 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 2 inclusion and 14 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: finished, as of the sponsor's last update on 16 Sep 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To map the physiological fMRI BOLD response, the brain electrical activity through MEG response and the blood flow, presynaptic and post-synaptic dopaminergic function through PET studies during different cognitive tasks (time frame: ongoing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001247, which also lists 4 linked publications.
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 16 Sep 2026.