Cognitive ImpairmentEarly Phase 1NCT03842800
Characterizing Clinical and Pharmacological Neuroimaging Biomarkers
A Early Phase 1 study testing MRI and Ketamine in people with Cognitive Impairment, run by Yale University at 1 site in United States.
Trial summary
This study is part of a larger overall study that seeks to characterize clinical and pharmacological neuroimaging biomarkers. The purpose of this registered protocol is understand the effect of emotion on cognitions by specifically examining the effect of reward processing on working memory in patients with… Read more about this study
- Who is it for?
- Ages 16 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Cognitive Impairment
- What is being tested?
- MRI and Ketamine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 143 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2013to 31 Aug 2018
- Phase
- Early Phase 1
- 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 16 to 60 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- For BOTH Non-Healthy Controls and Healthy Controls:
- Right-handed as determined by the Edinburgh handedness questionnaire (Oldfield, 1971).
- Premorbid IQ>70 determined by WAIS similarities and matrix reasoning subtests; Any history indicating learning disability, mental retardation, or attention deficit disorder will exclude the subject from participation.
- Must speak or read English at least 8th grade level or higher and to complete study evaluations.
- Must have intact vision or vision that can be corrected by glasses or contact lenses (corrected 20 20/20).
- Must be able to tolerate enclosed spaces ** only if participating in MRI portion.
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- Female subjects must be postmenopausal for a least 1 year, surgically sterile, or using a reliable method of contraception at screening. Reliable methods of contraception include double-barrier methods (e.g. condom and diaphragm, condom and foam, condom and sponge), intrauterine devices, or hormonal birth control methods. Women with positive serum pregnancy results at screening or self-reporting of pregnancy will be excluded from the study. ** only if participating in MRI portion.
- Must be free of metallic foreign objects in body, such as aneurysm clips or pacemakers, or a questionable history of metallic fragments ** only if participating in MRI portion.
- For Non-Healthy Controls Participants:
- Adult patients from the community meeting diagnostic criteria for schizophrenia, schizoaffective disorder, psychosis at risk syndrome, Major Depressive Disorder or autism spectrum disorders.
- Young adults (16-21) who are at risk of developing schizophrenia (have "prodromal schizophrenia") may be involved in the study.
Who cannot join
- For Healthy Controls:
- Evidence or history of serious medical or physical conditions, including severe endocrine disorder (Cushing's, Lupus), heart disorder (past history of heart attacks, angina), or other major systemic medical conditions (kidney, MS, CP, blindness, serious physical disability).
- Neurological conditions that might confound the results, including past stroke, seizures, dementia, brain tumor, brain surgery, neurological disease, head injury, or severe concussion (lasting >2 minutes in their life).
- Individual not larger than 55" around shoulders and widest part of chest (approx. 250lb limit) ** only if participating in MRI portion.
- Any other condition that is contra-indicated for fMRI if selected to participate in fMRI portion as determined by the MRRC safety screen. ** only if participating in MRI portion.
- Meeting current diagnostic criteria for any DSM-IV Axis I psychiatric disorders, determined by SCID-NP / MINI interviews.
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- First-degree relative with Axis I DSM-IV disorder.
- Regular use of psychoactive drugs including anxiolytics and antidepressants.
- Meeting current DSM-IV abuse and/or dependence diagnostic criteria for other substances, other than nicotine in the past 6 months as determined by SCID-NP / MINI interviews (excluding caffeine).
- For Non-Healthy Controls:
- Medical. Evidence or history of serious medical or physical conditions, including severe endocrine disorder (Cushing's, Lupus), heart disorder (past history of heart attacks, angina), or other major systemic medical conditions (kidney, MS, CP, blindness, serious physical disability).
- Neurological conditions that might confound the results, including past stroke, seizures, dementia, brain tumor, brain surgery, neurological disease, head injury, or severe concussion (lasting >2 minutes in your lifetime).
- Individual not larger than 55" around shoulders and widest part of chest (approx. 250lb limit) ** only if participating in MRI portion.
- Any other condition that is contra-indicated for fMRI if selected to participate in fMRI portion as determined by the MRRC safety screen. ** only if participating in MRI portion.
- Meeting current diagnostic criteria for primary DSM-IV anxiety, depression or ADHD, determined by SCID-NP / MINI interview due to possible effects on cognition.
- Medication change within the past 2 weeks to avoid transient effects of medication regiment change; medication type and dose will be carefully recorded and used as a covariate in all analyses. Of note, if patients are not on medication (but are clinically stable) they will be invited to participate.
- History of any substance dependence disorder meeting DSM-IV criteria with the exception of nicotine and caffeine in the past 6 months. Meeting DSM-IV abuse and/or dependence diagnostic criteria for other substances in the past 6 months as determined by SCID / MINI interviews (again excluding caffeine and nicotine). Study will exclude for Specific Patterns of Substance Use. In addition, the study will exclude for use of stimulants, alcohol or heavy continued substance use defined as at least 3+ days per week for the duration of the last 6 months. In particular, we will not exclude for sporadic use of cannabis (defined as 3 or fewer marijuana cigarettes per week). Also, the study will exclude if a participant reports heavy habitual marijuana use, which we define more than 3 marijuana cigarettes per week over at least 90% of the weeks during a period of 6 months or more. Patterns of drug class, use pattern, frequency and history as well as the urine toxicology on the day of the assessment as well as all longitudinal followups will be assessed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Magnetic Resonance Research Center
New Haven, Connecticut, 06520-8043
About this study
This study is part of a larger overall study that seeks to characterize clinical and pharmacological neuroimaging biomarkers. The purpose of this registered protocol is understand the effect of emotion on cognitions by specifically examining the effect of reward processing on working memory in patients with schizophrenia.
Read the detailed description
Cognition rarely occurs in the 'real world' in isolation, and typically occurs under emotional influences that may alter how cognition occurs. Understanding these motivational and cognitive interactions will help better assess mechanisms that underlie the cognitive and negative symptoms of schizophrenia.
To better understand the effect of emotion on cognitions, this study will examine the effect of reward processing on working memory in patients with schizophrenia. To this end, this will be a two-pronged approach.
The first prong, is to understand the neural mechanisms of incentivized spatial working memory processes. fMRI will be used and a paradigm will be employed that combines reward processing and working memory to understand how patients with schizophrenia recruit neural systems in response to rewarded working memory.
To further understand this, this study will compare the neural effects in patients with schizophrenia with patients with depression, another group of psychiatric patients who also suffer from cognitive and motivational deficits. Both of these groups suffer from cognitive and motivational deficits, yet the treatments and disease presentations differ.
It is hypothesized that the ways in which cognitive and motivational processes interact in the brain will have some similarities, but also differences, that distinguish the two psychiatric illnesses. As part of this aim, a group of typical, healthy adults subjects will be recruited as a control. A subset of healthy participants that passed the medical and psychiatric screen will be invited to participate in the ketamine portion of the study which will be completed during the MRI session.
- Conditions
- Cognitive Impairment
- Being tested
- MRI, Ketamine
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRIOther
Also called Magnetic Resonance Imaging
Patients and volunteers will receive an MRI.
KetamineDrug
Ketamine will be administered to a subset of healthy controls that agree to receive the drug as part of receiving an MRI.
| Study group | Role | What they receive |
|---|---|---|
| ASD Patients | Other | This arm consists of patients diagnosed with Autism Spectrum Disorder (ASD) that will receive an MRI. Receives: Other: MRI |
| Schizophrenic Patients | Other | This arm consists of patients diagnosed with Schizophrenia that will receive an MRI. Receives: Other: MRI |
| Healthy Controls | Other | This arm consists of healthy control volunteer participants that will receive an MRI. Receives: Other: MRI |
| Healthy Controls with Ketamine | Experimental | This arm consists of healthy control volunteer participants that elect to receive ketamine prior to receiving an MRI. Receives: Other: MRI; Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Working Memory (WM)
The tool used to measure working memory (WM) is a spatial working memory task. We measure angular accuracy of spatial working memory, and better accuracy is indicated by a lower angular distance. Subjects are asked to centrally fixate, and a circle appears on the screen briefly, and then disappears. Afterwards they see a gray circle that is linked to a joystick and are asked to move the gray circle to where they best remembered the initial circle to be. We care about the angular distance between where the initial circle appeared and where they placed the gray circle. The low range is 0 degrees, and the high range is 180 degrees. Scores are presented as averages and standard deviations.
Measured: Up to 2 hours
Secondary outcomes (3)
Behavior
The tool used to measure behavior is a spatial working memory task. We measure angular accuracy of spatial working memory, and better accuracy is indicated by a lower angular distance. We expect that patients with schizophrenia would have higher angular distances (ie, worse accuracy) than healthy control subjects on placebo, and patients with ASD. We expect that HCS on ketamine would have higher angular distances (ie worse accuracy), compared to when they are not on ketamine, and that this would approach the performance of patients with SCZ. The low range is 0 degrees, and the high range is 180 degrees. Scores are presented as averages and standard deviations.
Measured: Up to 2 hours
BOLD
Regional BOLD (blood oxygen dependent) signal in the dorsolateral prefrontal cortex and parietal cortex. BOLD signal refers to the blood oxygen level dependent signal change measured using functional magnetic resonance imaging. It is an indirect marker of neural activity. The time series of BOLD signal changes is entered into a general linear model with our events of interest (WM maintenance) and we do statistics on the resulting beta weights.
Measured: Up to 2 hours
Whole brain connectivity
Whole-brain connectivity refers to the correlation in time series between voxels. These analysis will specifically focus on the delay period subjects are maintaining a spatial location.
Measured: Up to 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2019
- Study start1 Apr 2013
- Primary completion31 Aug 2018
- Study completion31 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 143 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alan Anticevic, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03842800
- Sponsor's protocol ID
- 1111009332
- Status last verified
- Jun 2020
- First submitted
- 14 Feb 2019
- Last updated
- 1 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterizing Clinical and Pharmacological Neuroimaging Biomarkers
- ClinicalTrials.gov ID
- NCT03842800
- Acronym / sponsor ID
- 1111009332
- Conditions
- Cognitive Impairment
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 143 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 1 Apr 2013 (actual)
- Primary completion
- 31 Aug 2018 (actual)
- Study completion
- 31 Aug 2018 (actual)
- First posted
- 15 Feb 2019 (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.
This study is part of a larger overall study that seeks to characterize clinical and pharmacological neuroimaging biomarkers. The purpose of this registered protocol is understand the effect of emotion on cognitions by specifically examining the effect of reward processing on working memory in patients with schizophrenia.
Detailed description
Cognition rarely occurs in the 'real world' in isolation, and typically occurs under emotional influences that may alter how cognition occurs. Understanding these motivational and cognitive interactions will help better assess mechanisms that underlie the cognitive and negative symptoms of schizophrenia.
To better understand the effect of emotion on cognitions, this study will examine the effect of reward processing on working memory in patients with schizophrenia. To this end, this will be a two-pronged approach.
The first prong, is to understand the neural mechanisms of incentivized spatial working memory processes. fMRI will be used and a paradigm will be employed that combines reward processing and working memory to understand how patients with schizophrenia recruit neural systems in response to rewarded working memory.
To further understand this, this study will compare the neural effects in patients with schizophrenia with patients with depression, another group of psychiatric patients who also suffer from cognitive and motivational deficits. Both of these groups suffer from cognitive and motivational deficits, yet the treatments and disease presentations differ.
It is hypothesized that the ways in which cognitive and motivational processes interact in the brain will have some similarities, but also differences, that distinguish the two psychiatric illnesses. As part of this aim, a group of typical, healthy adults subjects will be recruited as a control. A subset of healthy participants that passed the medical and psychiatric screen will be invited to participate in the ketamine portion of the study which will be completed during the MRI session.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ASD Patients | Other | Other: MRIThis arm consists of patients diagnosed with Autism Spectrum Disorder (ASD) that will receive an MRI. |
| Schizophrenic Patients | Other | Other: MRIThis arm consists of patients diagnosed with Schizophrenia that will receive an MRI. |
| Healthy Controls | Other | Other: MRIThis arm consists of healthy control volunteer participants that will receive an MRI. |
| Healthy Controls with Ketamine | Experimental | Other: MRI, Drug: KetamineThis arm consists of healthy control volunteer participants that elect to receive ketamine prior to receiving an MRI. |
Who may qualify
- Ages
- 16 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- For BOTH Non-Healthy Controls and Healthy Controls:
- Right-handed as determined by the Edinburgh handedness questionnaire (Oldfield, 1971).
- Premorbid IQ>70 determined by WAIS similarities and matrix reasoning subtests; Any history indicating learning disability, mental retardation, or attention deficit disorder will exclude the subject from participation.
- Must speak or read English at least 8th grade level or higher and to complete study evaluations.
- Must have intact vision or vision that can be corrected by glasses or contact lenses (corrected 20 20/20).
Key exclusion criteria (17 listed)
- For Healthy Controls:
- Evidence or history of serious medical or physical conditions, including severe endocrine disorder (Cushing's, Lupus), heart disorder (past history of heart attacks, angina), or other major systemic medical conditions (kidney, MS, CP, blindness, serious physical disability).
- Neurological conditions that might confound the results, including past stroke, seizures, dementia, brain tumor, brain surgery, neurological disease, head injury, or severe concussion (lasting >2 minutes in their life).
- Individual not larger than 55" around shoulders and widest part of chest (approx. 250lb limit) ** only if participating in MRI portion.
- Any other condition that is contra-indicated for fMRI if selected to participate in fMRI portion as determined by the MRRC safety screen. ** only if participating in MRI portion.
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 |
|---|---|---|
| MRIAlso: Magnetic Resonance ImagingPatients and volunteers will receive an MRI. | Other | ASD Patients, Healthy Controls, Healthy Controls with Ketamine, Schizophrenic Patients |
| KetamineKetamine will be administered to a subset of healthy controls that agree to receive the drug as part of receiving an MRI. | Drug | Healthy Controls with Ketamine |
Primary outcome
Working Memory (WM)
Time frame: Up to 2 hours
The tool used to measure working memory (WM) is a spatial working memory task. We measure angular accuracy of spatial working memory, and better accuracy is indicated by a lower angular distance. Subjects are asked to centrally fixate, and a circle appears on the screen briefly, and then disappears. Afterwards they see a gray circle that is linked to a joystick and are asked to move the gray circle to where they best remembered the initial circle to be. We care about the angular distance between where the initial circle appeared and where they placed the gray circle. The low range is 0 degrees, and the high range is 180 degrees. Scores are presented as averages and standard deviations.
3 secondary outcomes
Behavior
Time frame: Up to 2 hours
BOLD
Time frame: Up to 2 hours
Whole brain connectivity
Time frame: Up to 2 hours
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 1 Jul 2020.
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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.
Alan Anticevic, PhD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing MRI and Ketamine in people with Cognitive Impairment, run by Yale University 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 11 inclusion and 17 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 1 Jul 2020. 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Working Memory (WM) (time frame: Up to 2 hours). 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 1 Jul 2020.