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Inpatient Evaluation of Adults With Schizophrenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00001247
Recruitment Status : Recruiting
First Posted : November 4, 1999
Last Update Posted : May 26, 2023
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Study Description
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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.

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Condition or disease Intervention/treatment
Schizophrenia Drug: Sirolimus

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
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Study Type : Observational
Estimated Enrollment : 700 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Inpatient Evaluation of Neuropsychiatric Patients
Actual Study Start Date : September 15, 1989

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
Drug Information available for: Sirolimus

Groups and Cohorts
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Group/Cohort Intervention/treatment
1
Individuals with schizophrenia-spectrum illness from the community.
 Drug: Sirolimus


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. 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.


Secondary Outcome Measures :
  1. PANSS data will be collected to determine changes or lack thereof in clinical status during the protocol. [ Time Frame: Ongoing ]
    PANSS data will be collected to determine changes or lack thereof in clinical status during the protocol.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Individuals with schizophrenia-spectrum illness from the community.
Criteria
  • INCLUSION CRITERIA:
  • Age 18 or older
  • Male or female
  • Diagnosis of Schizophrenia, Schizoaffective Disorder or 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 schizophrenia, schizoaffective disorder or psychosis NOS.

EXCLUSION CRITERIA:

  • 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. Most such medications require a 6-month washout period, but some with shorter elimination half-lives, such as risperidone powder (Risperdal Consta), only require 3 months. Subjects may complete the last 3 months of washout in the inpatient unit while being evaluated during the Screening Evaluation and Stabilization Phase.
  • 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.
  • Infection with syphilis, hepatitis, or HIV.
  • History of of any (excepting nicotine-related) DSM5-defined moderate to severe substance use disorder (or DSM-IV-defined substance dependence).
  • Cumulative lifetime history of any (excepting nicotine-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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001247


Contacts
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Contact: Vincent L Del Balzo (301) 435-8974 vincent.delbalzo@nih.gov
Contact: Daniel P Eisenberg, M.D. (301) 402-5483 eisenbergd@mail.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Daniel P Eisenberg, M.D. National Institute of Mental Health (NIMH)
More Information
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Additional Information:

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT00001247    
Other Study ID Numbers: 890160
89-M-0160
First Posted: November 4, 1999    Key Record Dates
Last Update Posted: May 26, 2023
Last Verified: May 8, 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: .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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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) ):
Schizophrenia
Psychosis
Schizoaffective
 Neuroimaging
Cognition
Schizoaffective Disorder
Additional relevant MeSH terms:
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Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
 Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs