Effects of Ketamine and Risperidone on Cognition (Schiz_2)
Recruitment status was Not yet recruiting
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.
Drug: placebo to match risperidone
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
|Official Title:||Effects of NMDA Receptor Antagonism on Cognitive Processes in Healthy Volunteers and Its Reversal by a Dopamine Antagonist: Comparison to Patients With Schizophrenia|
- Biconditional learning task [ Time Frame: 6 months ] [ Designated as safety issue: No ]Accuracy (% correct) for simple and biconditional learning trials, averaged over 8 blocks
- Eye movement task [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- 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.
- Salience Attribution task [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- 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.
- Signal detection task [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- d׳ value
- Hits, when participants respond positively and a voice is present.
- False alarm rate.
- β value.
- N-Back [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Correct responses across three levels of difficulty.
- Percentage of overall responses that was correct.
- Errors of omission.
- Errors of commission.
- Spatial working memory [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- 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
- Verbal Fluency [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- 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.
- Event-related potentials (Manchester EEG pilot study only) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- 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
- Questionnaires and assessment scale scores [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Effects of Drug Rating Scale.
- Pharmacogenomic analysis [ Time Frame: 12 months ] [ Designated as safety issue: No ]An exploratory genetic analysis aiming to correlate any genetic polymorphisms associated with schizotypy, schizophrenia or brain development with study outcomes.
|Study Start Date:||June 2010|
|Estimated Study Completion Date:||December 2010|
|Estimated Primary Completion Date:||November 2010 (Final data collection date for primary outcome measure)|
|Experimental: ketamine and risperidone||
ketamine infusion to achieve plasma concentrations of 100 ng/mL. Duration approximately 3 hoursDrug: risperidone
risperidone (2 mg) capsule. One dosing of 2 mg.
|Active Comparator: ketamine and placebo||
ketamine infusion to achieve plasma concentrations of 100 ng/mL. Duration approximately 3 hoursDrug: placebo to match risperidone
placebo capsule to match risperidone 2 mg capsule
|Active Comparator: saline and risperidone||
risperidone (2 mg) capsule. One dosing of 2 mg.Drug: saline
saline infusion. Duration approximately 3 hours
|Placebo Comparator: saline and placebo||
saline infusion. Duration approximately 3 hoursDrug: placebo to match risperidone
placebo capsule to match risperidone 2 mg capsule
No Intervention: Patients with Schizophrenia
Patients with schizophrenia will not receive study drug and will not undergo randomisation.
This study is a continuation from a previous study (P1V-SCH-CT01-07). The overall aim of the 2 studies is to identify and validate potential biomarker tasks that may be used to provide early indications into the use of new treatments for schizophrenia. The studies are considering two potential models for schizophrenia in healthy volunteers, the first model looks at high versus average schizotypy, schizotypy being a personality trait. The second model, explored in this study, is a ketamine infusion.
Healthy volunteers will be identified through advertising and will initially be asked to complete an online questionnaire.Suitability for the next stage of the study will be based on the responses to the online questionnaire. Telephone interviews will then be conducted to assess suitability for screening.Screening visits will then be carried out in which a full medical and lab screening is undertaken. participants will also complete a number of psychiatric questionnaires and interviews. If participants remain suitable they will be invited to an assessment day in which they will be randomised to one of four study medication arms. Participants will then complete the biomarker tasks followed by questionnaires, rating scales and interviews. Patients with schizophrenia will form the 5th study arm and will not receive medication. They will complete the biomarkers in the same way as healthy volunteers.87 participants are planned, 72 healthy volunteers, 15 patients with schizophrenia.
This study does not test any investigational medicinal product (IMP) so any ethical issues that are associated with introducing a participant to a study drug are not applicable in this study.
Ketamine is already a widely used anaesthetic agent but when given at sub-anaesthetic doses is a useful tool for modelling schizophrenia psychosis.
The current study aims to assess the sensitivity of a battery of biomarker tasks (biomarkers are measures of processes that go wrong in illnesses and that contribute to symptoms) to the cognitive deficits induced by ketamine.
It may in future be possible to evaluate the effects of novel treatment for schizophrenia in healthy volunteers using this model, which would then potentially provide a rapid indication of the potential efficacy of candidate compounds at an early phase of drug development .
The study will provide information about the sensitivity of the biomarker tasks in detecting the effects of the pharmacological treatments for schizophrenia in healthy volunteers.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01140620
|Contact: Professor Bill Deakin||0161 275 firstname.lastname@example.org|
|Institute of Psychiatry, King's College London||Not yet recruiting|
|London, Greater London, United Kingdom, SE5 8AF|
|Contact: Professor Steve Williams 020 7848 3060 Steven.email@example.com|
|Contact: Rita Abdulahad-Olivera +44 (0) 1865 522 285 firstname.lastname@example.org|
|Principal Investigator: Professor Steve Williams|
|School of Psychology, University of Cardiff||Not yet recruiting|
|Cardiff, United Kingdom, CF10 3AT|
|Contact: Dr James Walters +44 (0) 2920875271 email@example.com|
|Contact: Anne Barron +44(0)2921250053 firstname.lastname@example.org|
|Principal Investigator: Dr James Walters|
|Sub-Investigator: Professor Lawrence Wilkinson|
|University of Manchester (Dept of Neuropyschiatry)||Not yet recruiting|
|Manchester, United Kingdom, M13 9PT|
|Principal Investigator: Professor Bill Deakin|
|Principal Investigator:||Professor Bill Deakin||University of Manchester|