Inpatient Evaluation of Adults With Schizophrenia

NCT00001247 | Completed

• 2 other identifiers: 89016089-M-0160
• Study Type: observational
• Target: 648
• Locations: 1 country
• Sites: 1

Brief 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. 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....

Conditions

Schizophrenia

Keywords

Schizophrenia; Psychosis; Schizoaffective; Neuroimaging; Cognition; Schizoaffective Disorder

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  ongoing

Secondary Outcomes (1)

• PANSS data will be collected to determine changes or lack thereof in clinical status during the protocol.

  Ongoing

Study Arms (1)

1

Individuals with schizophrenia-spectrum illness from the community.

Drug: Sirolimus

Interventions

Sirolimus DRUG

Drug not used in study.

1

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with schizophrenia-spectrum illness from the community.

You may qualify if:

• 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.

You may not qualify if:

• 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 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.
• 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.
• 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

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 11381111 BACKGROUND

• Meyer-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.

  PMID: 11865311 BACKGROUND

• Rubinstein 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.

  PMID: 36772948 DERIVED

• Eisenberg 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.

  PMID: 34789848 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Daniel P Eisenberg, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: September 15, 1989
• Last Updated: May 7, 2026

Record last verified: 2026-02-27

Locations

US (1)