SchizophreniaNCT00937716
Treatment Response in Schizophrenia: Bridging Imaging and Postmortem Studies
An observational study of Schizophrenia, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
The overarching goal is to identify imaging markers that will predict treatment response, and to confirm or validate these biomarkers using anatomical studies of postmortem tissue. Read more about this study
- Who is it for?
- Ages 19 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to 30 Jun 2021
- 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 19 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: We will recruit fifty patients with a diagnosis of schizophrenia presenting at UAB clinics who have stopped taking APD medication for at least 10 days and agree to antipsychotic treatment, and twenty-five matched healthy volunteers.
Who may be able to join
- Normal volunteers or schizophrenic patients between the age of 19 and 55.
Who cannot join
- Individuals with a diagnosable central nervous system illness.
- Major medical condition, active substance abuse or dependence, pregnancy, or history of head trauma.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham, Department of Psychiatry, SC 501
Birmingham, Alabama, 35294
About this study
The overarching goal is to identify imaging markers that will predict treatment response, and to confirm or validate these biomarkers using anatomical studies of postmortem tissue. Early detection of drug response would yield specific treatment strategies that are tailored to the individual, thus improving both the quality of life of the patients and drastically reducing the costs associated with unsuccessful treatment strategies.
Read the detailed description
Our past brain imaging and Positron Emission Tomography (PET) studies have contributed to the understanding of specific brain regions related to treatment response to antipsychotic drugs in schizophrenia. We have found that treatment response to antipsychotic medication is related to blood-flow patterns in specific regions (such as the ventral striatum, anterior cingulate cortex, and hippocampus). In addition, functional changes in these regions following one week of antipsychotic drug therapy are predictive of treatment response. Dr. Roberts, a neuroanatomist, has studied the post mortem (after death) brains of patients with schizophrenia while working in association with the Maryland Brain Collection. Her studies have indicated an increased number of dopaminergic synapses (that is, neurons that produce the neurotransmitter dopamine) in these regions in patients who were known to have had a favorable response to antipsychotic drug therapy. In addition, from this post-mortem work we know the number of glutamate synapses in these regions were significantly different between good treatment responders and poor responders.
From these studies we have hypothesized that in schizophrenia an over-abundance of dopamine in the ventral striatum interferes with normal functioning by limiting the transmission of glutamate. Putatively, antipsychotic medications may decrease the symptoms of schizophrenia by restoring glutamatergic activity in the ventral striatum and projected areas, such as the anterior cingulate cortex and hippocampus. We have hypothesized that those individuals responding favorably to antipsychotic drug therapy will display greater glutamate activity in the ventral striatum (due to dopamine blockade) and the other regions receiving glutamate projections. This should lead to restored neuronal functioning in good responders when compared to treatment resistant and poor responders to antipsychotic drug treatment. We will test this hypothesis using complementary imaging and postmortem studies yielding data that will permit the formulation of a comprehensive model for antipsychotic drug responses in subjects with severe mental illness.
Magnetic Resonance is a technique for probing atoms and molecules based upon their interaction with an external magnetic field. Magnetic Resonance does not use ionizing radiation. The most familiar example of this is Magnetic Resonance Imaging (MRI). Another application of Magnetic Resonance is called functional Magnetic Resonance Imaging (fMRI). Functional Magnetic Resonance Imaging (fMRI) allows us to measure the Blood Oxygenation Level-Dependent (BOLD) response, a measure of blood flow in the brain that is known to correlate with neuronal activity. Another application of Magnetic Resonance is Magnetic Resonance Spectroscopy (MRS), which allows the measurements of specific metabolites such as N-acetyl aspartate (NAA), a measure of neuronal integrity, and Glutamate, which is involved in neurotransmission and metabolism. We will seek to replicate and extend our past Positron Emission Tomography (PET) findings with functional magnetic resonance imaging (fMRI) using cognitive tasks that are known to activate the hippocampus (Episodic memory task) and the anterior cingulate cortex (Stroop task). This aim will further seek to parse out the differential contribution of the hippocampus and the anterior cingulate cortex to treatment response. At the same time, N-acetylaspartate, a marker of neuronal integrity, and glutamate measurements obtained with magnetic resonance spectroscopy in the anterior cingulate cortex and hippocampus will directly probe in the living brain the relation between neuronal integrity, glutamate function, and treatment response. In parallel, the postmortem work of Dr. Roberts (UAB IRB exemption: NO70813001, IRB#F080306003) will concentrate on the study of the anterior cingulate cortex in post mortem brains of schizophrenic patients. These studies should allow the development of hypotheses about the pathophysiology of treatment response and provide a basis for the interpretation of functional imaging data. The overarching goal is to identify imaging markers that will predict treatment response, and to confirm or validate these biomarkers using anatomical studies of postmortem tissue. Early detection of drug response would yield specific treatment strategies that are tailored to the individual, thus improving both the quality of life of the patients and drastically reducing the costs associated with unsuccessful treatment strategies.
- Conditions
- Schizophrenia
- Keywords
- schizophrenia, treatment response, risperidone, functional magnetic resonance, functional magnetic spectroscopy
- Medical subject headings
- Schizophrenia
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 |
|---|---|---|
| Diagnosis of Schizophrenia | Patients with a diagnosis of schizophrenia that have been off antipsychotic medicine and would like to resume treatment will be enrolled in the study. | |
| Healthy Volunteers | Healthy Volunteers without a psychiatric diagnosis, central nervous system condition, serious head injury, or current drug use will be matched on an individual basis to schizophrenic participants and used as a control population. |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate whether MRI signals (both fMRI and 1H-MRS) predictive of treatment response to antipsychotic therapy in schizophrenia.
Measured: at conclusion of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2009 (estimated)
- Study startOct 2008
- Primary completion31 Dec 2020
- Study completion30 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Adrianne C Lahti, University of Alabama at Birmingham
- Investigators
- Adrienne C Lahti, MD, Principal investigator, University of Alabama at Birmingham, Department of Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00937716
- Sponsor's protocol ID
- F080807011
- Status last verified
- Jul 2021
- First submitted
- 9 Jul 2009
- Last updated
- 26 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment Response in Schizophrenia: Bridging Imaging and Postmortem Studies
- ClinicalTrials.gov ID
- NCT00937716
- Acronym / sponsor ID
- F080807011
- Conditions
- Schizophrenia
- Keywords
- schizophrenia, treatment response, risperidone, functional magnetic resonance, functional magnetic spectroscopy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- Oct 2008
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 13 Jul 2009 (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 overarching goal is to identify imaging markers that will predict treatment response, and to confirm or validate these biomarkers using anatomical studies of postmortem tissue. Early detection of drug response would yield specific treatment strategies that are tailored to the individual, thus improving both the quality of life of the patients and drastically reducing the costs associated with unsuccessful treatment strategies.
Detailed description
Our past brain imaging and Positron Emission Tomography (PET) studies have contributed to the understanding of specific brain regions related to treatment response to antipsychotic drugs in schizophrenia. We have found that treatment response to antipsychotic medication is related to blood-flow patterns in specific regions (such as the ventral striatum, anterior cingulate cortex, and hippocampus). In addition, functional changes in these regions following one week of antipsychotic drug therapy are predictive of treatment response. Dr. Roberts, a neuroanatomist, has studied the post mortem (after death) brains of patients with schizophrenia while working in association with the Maryland Brain Collection. Her studies have indicated an increased number of dopaminergic synapses (that is, neurons that produce the neurotransmitter dopamine) in these regions in patients who were known to have had a favorable response to antipsychotic drug therapy. In addition, from this post-mortem work we know the number of glutamate synapses in these regions were significantly different between good treatment responders and poor responders.
From these studies we have hypothesized that in schizophrenia an over-abundance of dopamine in the ventral striatum interferes with normal functioning by limiting the transmission of glutamate. Putatively, antipsychotic medications may decrease the symptoms of schizophrenia by restoring glutamatergic activity in the ventral striatum and projected areas, such as the anterior cingulate cortex and hippocampus. We have hypothesized that those individuals responding favorably to antipsychotic drug therapy will display greater glutamate activity in the ventral striatum (due to dopamine blockade) and the other regions receiving glutamate projections. This should lead to restored neuronal functioning in good responders when compared to treatment resistant and poor responders to antipsychotic drug treatment. We will test this hypothesis using complementary imaging and postmortem studies yielding data that will permit the formulation of a comprehensive model for antipsychotic drug responses in subjects with severe mental illness.
Magnetic Resonance is a technique for probing atoms and molecules based upon their interaction with an external magnetic field. Magnetic Resonance does not use ionizing radiation. The most familiar example of this is Magnetic Resonance Imaging (MRI). Another application of Magnetic Resonance is called functional Magnetic Resonance Imaging (fMRI). Functional Magnetic Resonance Imaging (fMRI) allows us to measure the Blood Oxygenation Level-Dependent (BOLD) response, a measure of blood flow in the brain that is known to correlate with neuronal activity. Another application of Magnetic Resonance is Magnetic Resonance Spectroscopy (MRS), which allows the measurements of specific metabolites such as N-acetyl aspartate (NAA), a measure of neuronal integrity, and Glutamate, which is involved in neurotransmission and metabolism. We will seek to replicate and extend our past Positron Emission Tomography (PET) findings with functional magnetic resonance imaging (fMRI) using cognitive tasks that are known to activate the hippocampus (Episodic memory task) and the anterior cingulate cortex (Stroop task). This aim will further seek to parse out the differential contribution of the hippocampus and the anterior cingulate cortex to treatment response. At the same time, N-acetylaspartate, a marker of neuronal integrity, and glutamate measurements obtained with magnetic resonance spectroscopy in the anterior cingulate cortex and hippocampus will directly probe in the living brain the relation between neuronal integrity, glutamate function, and treatment response. In parallel, the postmortem work of Dr. Roberts (UAB IRB exemption: NO70813001, IRB#F080306003) will concentrate on the study of the anterior cingulate cortex in post mortem brains of schizophrenic patients. These studies should allow the development of hypotheses about the pathophysiology of treatment response and provide a basis for the interpretation of functional imaging data. The overarching goal is to identify imaging markers that will predict treatment response, and to confirm or validate these biomarkers using anatomical studies of postmortem tissue. Early detection of drug response would yield specific treatment strategies that are tailored to the individual, thus improving both the quality of life of the patients and drastically reducing the costs associated with unsuccessful treatment strategies.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Diagnosis of Schizophrenia | – | –Patients with a diagnosis of schizophrenia that have been off antipsychotic medicine and would like to resume treatment will be enrolled in the study. |
| Healthy Volunteers | – | –Healthy Volunteers without a psychiatric diagnosis, central nervous system condition, serious head injury, or current drug use will be matched on an individual basis to schizophrenic participants and used as a control population. |
Who may qualify
- Ages
- 19 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- We will recruit fifty patients with a diagnosis of schizophrenia presenting at UAB clinics who have stopped taking APD medication for at least 10 days and agree to antipsychotic treatment, and twenty-five matched healthy volunteers.
Key inclusion criteria (1 listed)
- Normal volunteers or schizophrenic patients between the age of 19 and 55.
Key exclusion criteria (2 listed)
- Individuals with a diagnosable central nervous system illness.
- Major medical condition, active substance abuse or dependence, pregnancy, or history of head trauma.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To evaluate whether MRI signals (both fMRI and 1H-MRS) predictive of treatment response to antipsychotic therapy in schizophrenia.
Time frame: at conclusion of study
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 26 Jul 2021.
- Individual participant dataSharing planned: No
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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.
Adrienne C Lahti, MD principal investigator
University of Alabama at Birmingham, Department of Psychiatry
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 University of Alabama at Birmingham 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 1 inclusion and 2 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 26 Jul 2021. 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 evaluate whether MRI signals (both fMRI and 1H-MRS) predictive of treatment response to antipsychotic therapy in schizophrenia. (time frame: at conclusion of study). 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 26 Jul 2021.