Schizophrenia Clinical Trial
— Schiz_2Official title:
Effects of NMDA Receptor Antagonism on Cognitive Processes in Healthy Volunteers and Its Reversal by a Dopamine Antagonist: Comparison to Patients With Schizophrenia
Verified date | November 2016 |
Source | University of Manchester |
Contact | n/a |
Is FDA regulated | No |
Health authority | United Kingdom: Research Ethics Committee |
Study type | Interventional |
The primary objective of this study is:
• To determine the effects of ketamine, which blocks the ion-channel gated by the NMDA
receptor, on performance of cognitive tasks and the extent to which these effects can be
reversed by the dopamine receptor antagonist, risperidone.
The secondary objectives of this study are:
- To establish whether patients with schizophrenia are able to reliably complete the
biomarker test battery and to assess whether their responses are similar to healthy
volunteers treated with ketamine.
- To establish a multi-site recruitment and assessment capacity based on shared Standard
Operating Procedures across three study centres.
Status | Completed |
Enrollment | 87 |
Est. completion date | December 2010 |
Est. primary completion date | November 2010 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Both |
Age group | 18 Years to 45 Years |
Eligibility |
Inclusion Criteria: 5.2.1 General inclusion criteria (healthy and schizophrenia groups) - Male or female aged 18 to 45 years - Fluent English speakers, preferably with English as first language. - Normotensive with sitting (5 minutes) blood pressure of 100 to 140 mmHg systolic, and 60 to 90 mmHg diastolic. - Negative alcohol breath test. - Negative urine drug screen. - Participant must have consumed only their normal intake of coffee or tea on the morning of the assessment day and not consumed any other beverages containing caffeine for 2 hours prior to the assessment visit. - Willing to follow the protocol prohibitions and restrictions . - Participant must have signed the informed consent form. - Those participants willing to participate in the pharmacogenomic components of the study must have signed the appropriate informed consent form. 5.2.2 Inclusion criteria applicable to healthy volunteers only - SPQ score of 21 to 36. - BMI of 18 to 30 kg/m². - Non-smoker or light smoker (less than 5 cigarettes per day). - Has not smoked in the 2 hours prior to the assessment visit. - Females should be surgically sterile or abstinent or practising an effective method of birth control; they should have a negative urine pregnancy test. - Healthy at screening and assessment visits as determined by the study physician, based on a medical evaluation including medical history, physical examination, laboratory tests, vital signs, 12-lead ECG and pre-study psychological tests. 5.2.3 Inclusion criteria applicable to participants with schizophrenia only - Documented history of a diagnosis of schizophrenia as confirmed by GP or psychiatrist or by previous research diagnostic interview. - Confirmation of diagnosis of schizophrenia, based on the MINI structured clinical interview, carried out by the study physician. - In good physical health at screening and assessment visits as determined by the study physician, based on a medical evaluation including medical history, physical examination, laboratory tests and vital signs1. Exclusion Criteria: 5.3.1 General exclusion criteria (healthy and schizophrenia groups) - History of alcohol or substance dependence. - Consumption of large amounts of caffeinated drinks. - Have received over-the-counter medicine within 48 hours prior to assessment visit (apart from paracetamol) unless it will not interfere with the study procedures or compromise safety. - History of, or current condition of, migraine headaches. - Significant hearing impairment which in the opinion of the Investigator may interfere with the performance of the psychological test battery. - Significant visual impairment or history of ocular treatment or ongoing condition which may interfere with the performance of the psychological test battery. - Participated in a trial with any drug within 84 days of assessment visit. - Unable or unwilling to comply with study procedures. 5.3.2 Exclusion criteria applicable to healthy volunteers only - Known or suspected hypersensitivity or intolerance to risperidone or any of their excipients. - Known or suspected hypersensitivity or intolerance to ketamine or any previous adverse reaction to anaesthesia. - If female: are pregnant or are trying to get pregnant or are currently breast feeding. - Relevant history, or presence upon clinical examination, of cardiac, ophthalmologic, gastro-intestinal, hepatic, or renal disease or other condition known to increase risk of side effects. - History or presence of neurological or psychiatric conditions. - Have received prescribed medication within 14 days prior to assessment visit (apart from the contraceptive pill) unless it will not interfere with the study procedures or compromise safety. 5.3.3 Exclusion criteria applicable to participants with schizophrenia only - Changes to antipsychotic medications within 30 days of assessment visit. - Admission to hospital, involvement with the home treatment team for psychiatric reasons or documented relapse of psychiatric symptoms within last 3 months. - History or presence of psychiatric or neurological conditions other than schizophrenia, major depression and generalised anxiety disorder. - Current extra-pyramidal symptoms and/or adverse effects from antipsychotic medications that, in the opinion of the study physician, will interfere with completion of the study tasks. |
Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science
Country | Name | City | State |
---|---|---|---|
United Kingdom | School of Psychology, University of Cardiff | Cardiff | |
United Kingdom | Institute of Psychiatry, King's College London | London | Greater London |
United Kingdom | University of Manchester (Dept of Neuropyschiatry) | Manchester |
Lead Sponsor | Collaborator |
---|---|
University of Manchester | Cardiff University, King's College London, P1vital Limited |
United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Biconditional learning task | Accuracy (% correct) for simple and biconditional learning trials, averaged over 8 blocks | 6 months | No |
Primary | Eye movement task | Antisaccade error rate. Antisaccade correction rate. Antisaccade latency. Antisaccade amplitude gain. Antisaccade peak velocity. Prosaccade error rate. Prosaccade correction rate. Prosaccade latency. Prosaccade amplitude gain. Prosaccade peak velocity. Smooth pursuit gain at three different target speeds. Smooth pursuit saccadic frequency at three different target speeds. |
6 months | No |
Primary | Salience Attribution task | Implicit aberrant salience (ms). i. Overall reaction time b.ii. Implicit adaptive salience (ms). c. Explicit adaptive salience (mm). d. Explicit aberrant salience (mm). e. Commission errors. f. Omission errors. |
6 months | No |
Primary | Signal detection task | d? value Hits, when participants respond positively and a voice is present. False alarm rate. ß value. |
6 months | No |
Primary | N-Back | Correct responses across three levels of difficulty. Percentage of overall responses that was correct. Errors of omission. Errors of commission. |
6 months | No |
Primary | Spatial working memory | Between search error rate - errors due to a participant returning to a treasure chest which had previously contained some treasure on an earlier trial within the same block. Within search error rate - errors due to a participant returning to the same treasure chest more than once within a trial. Average time to complete each difficulty level |
6 months | No |
Primary | Verbal Fluency | Number of words generated. Number of repetition errors: When the same word is repeated more than once within the letter or category. Number of set loss errors: These are: i.) Words that start with a letter which do not fit the trial; ii.) Words which are names of people or places or numbers; iii.) Grammatical variants of an already stated word; and iv.) Non-words. |
6 months | No |
Primary | Event-related potentials (Manchester EEG pilot study only) | Amplitude and latencies of the positive peak in the 80-160 ms range (P1) and the negative peak in the 160 - 250 ms range (N1) for the Kanitsa and non-Kanitsa conditions. Evoked gamma (30-100 Hz) and beta (14-30 Hz) oscillations in the 30 - 350 ms range to the Kanitsa condition. Evoked alpha (8-12 Hz) and theta (4-8 Hz) oscillations in the 30-500 ms range to both conditions. Coherence within and between frontal and occipital electrodes in the 100 - 400 ms range |
6 months | No |
Primary | Questionnaires and assessment scale scores | CADSS. BPRS. Effects of Drug Rating Scale. |
6 months | No |
Secondary | Pharmacogenomic analysis | An exploratory genetic analysis aiming to correlate any genetic polymorphisms associated with schizotypy, schizophrenia or brain development with study outcomes. | 12 months | No |
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