Effects of Ketamine and Risperidone on Cognition

NCT01140620 | Completed Phase 4

• 1 other identifier: P1V-SCH-CT02-09
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Healthy Volunteers; Schizophrenia

Keywords

NMDA receptor antagonism; cognitive processes; healthy volunteers; dopamine antagonist; schizophrenia

Outcome Measures

Primary Outcomes (9)

• Biconditional learning task

  Accuracy (% correct) for simple and biconditional learning trials, averaged over 8 blocks

  6 months

• Eye movement task

  1. Antisaccade error rate. 2. Antisaccade correction rate. 3. Antisaccade latency. 4. Antisaccade amplitude gain. 5. Antisaccade peak velocity. 6. Prosaccade error rate. 7. Prosaccade correction rate. 8. Prosaccade latency. 9. Prosaccade amplitude gain. 10. Prosaccade peak velocity. 11. Smooth pursuit gain at three different target speeds. 12. Smooth pursuit saccadic frequency at three different target speeds.

  6 months

• Salience Attribution task

  1. Implicit aberrant salience (ms). 2. 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

• Signal detection task

  1. d׳ value 2. Hits, when participants respond positively and a voice is present. 3. False alarm rate. 4. β value.

  6 months

• N-Back

  1. Correct responses across three levels of difficulty. 2. Percentage of overall responses that was correct. 3. Errors of omission. 4. Errors of commission.

  6 months

• Spatial working memory

  1. 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. 2. Within search error rate - errors due to a participant returning to the same treasure chest more than once within a trial. 3. Average time to complete each difficulty level

  6 months

• Verbal Fluency

  1. Number of words generated. 2. Number of repetition errors: When the same word is repeated more than once within the letter or category. 3. 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

• Event-related potentials (Manchester EEG pilot study only)

  1. 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. 2. Evoked gamma (30-100 Hz) and beta (14-30 Hz) oscillations in the 30 - 350 ms range to the Kanitsa condition. 3. Evoked alpha (8-12 Hz) and theta (4-8 Hz) oscillations in the 30-500 ms range to both conditions. 4. Coherence within and between frontal and occipital electrodes in the 100 - 400 ms range

  6 months

• Questionnaires and assessment scale scores

  1. CADSS. 2. BPRS. 3. Effects of Drug Rating Scale.

  6 months

Secondary Outcomes (1)

• Pharmacogenomic analysis

  12 months

Study Arms (5)

ketamine and risperidone

EXPERIMENTAL

Oral risperidone pretreatment and intravenous ketamine infusion

Drug: ketamine; Drug: risperidone

ketamine and placebo

ACTIVE COMPARATOR

Oral placebo risperidone pretreatment and intravenous ketamine infusion

Drug: ketamine; Drug: placebo risperidone

saline and risperidone

ACTIVE COMPARATOR

Oral risperidone pretreatment and intravenous saline infusion

Drug: risperidone; Drug: saline

saline and placebo

PLACEBO COMPARATOR

Oral placebo risperidone pretreatment and intravenous saline infusion

Drug: saline; Drug: placebo risperidone

Patients with Schizophrenia

NO INTERVENTION

Patients with schizophrenia will not receive study drug and will not undergo randomisation.

Interventions

ketamine DRUG

ketamine infusion to achieve plasma concentrations of 100 ng/mL. Duration approximately 3 hours

Also known as: ketalar

ketamine and placebo; ketamine and risperidone

risperidone DRUG

risperidone (2 mg) capsule. One dosing of 2 mg.

Also known as: risperdal

ketamine and risperidone; saline and risperidone

saline DRUG

saline infusion. Duration approximately 3 hours

saline and placebo; saline and risperidone

placebo risperidone DRUG

placebo capsule to match risperidone 2 mg capsule

Also known as: placebo risperdal

ketamine and placebo; saline and placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• Changes to antipsychotic medications within 30 days of assessment visit.

Sponsors & Collaborators

• University of Manchester: lead
• Cardiff University: collaborator
• King's College London: collaborator
• P1vital Limited: collaborator

Study Sites (3)

Institute of Psychiatry, King's College London

London, Greater London, SE5 8AF, United Kingdom

Location

University of Manchester (Dept of Neuropyschiatry)

Manchester, Manchester, M13 9PT, United Kingdom

Location

School of Psychology, University of Cardiff

Cardiff, CF10 3AT, United Kingdom

Location

Related Links

• website

MeSH Terms

Conditions

Schizophrenia

Interventions

Ketamine; Risperidone; Sodium Chloride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Professor Bill Deakin

  University of Manchester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: June 8, 2010
• First Posted: June 9, 2010
• Study Start: June 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: December 1, 2010
• Last Updated: November 9, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)