Effects of Ketamine and Risperidone on Cognition

NCT ID: NCT01140620

Last Updated: 2016-11-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

87 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-06-30

Study Completion Date

2010-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Healthy Volunteers Schizophrenia

Keywords

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NMDA receptor antagonism cognitive processes healthy volunteers dopamine antagonist schizophrenia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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ketamine and risperidone

Oral risperidone pretreatment and intravenous ketamine infusion

Group Type EXPERIMENTAL

ketamine

Intervention Type DRUG

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

risperidone

Intervention Type DRUG

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

ketamine and placebo

Oral placebo risperidone pretreatment and intravenous ketamine infusion

Group Type ACTIVE_COMPARATOR

ketamine

Intervention Type DRUG

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

placebo risperidone

Intervention Type DRUG

placebo capsule to match risperidone 2 mg capsule

saline and risperidone

Oral risperidone pretreatment and intravenous saline infusion

Group Type ACTIVE_COMPARATOR

risperidone

Intervention Type DRUG

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

saline

Intervention Type DRUG

saline infusion. Duration approximately 3 hours

saline and placebo

Oral placebo risperidone pretreatment and intravenous saline infusion

Group Type PLACEBO_COMPARATOR

saline

Intervention Type DRUG

saline infusion. Duration approximately 3 hours

placebo risperidone

Intervention Type DRUG

placebo capsule to match risperidone 2 mg capsule

Patients with Schizophrenia

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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ketamine

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

Intervention Type DRUG

risperidone

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

Intervention Type DRUG

saline

saline infusion. Duration approximately 3 hours

Intervention Type DRUG

placebo risperidone

placebo capsule to match risperidone 2 mg capsule

Intervention Type DRUG

Other Intervention Names

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ketalar risperdal placebo risperdal

Eligibility Criteria

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Inclusion Criteria

* 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.


* 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

* 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.
* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Cardiff University

OTHER

Sponsor Role collaborator

King's College London

OTHER

Sponsor Role collaborator

P1vital Limited

INDUSTRY

Sponsor Role collaborator

University of Manchester

OTHER

Sponsor Role lead

Responsible Party

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Bill Deakin

Professor of Psychiatry

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Professor Bill Deakin

Role: PRINCIPAL_INVESTIGATOR

University of Manchester

Locations

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Institute of Psychiatry, King's College London

London, Greater London, United Kingdom

Site Status

University of Manchester (Dept of Neuropyschiatry)

Manchester, Manchester, United Kingdom

Site Status

School of Psychology, University of Cardiff

Cardiff, , United Kingdom

Site Status

Countries

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United Kingdom

Related Links

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Other Identifiers

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P1V-SCH-CT02-09

Identifier Type: -

Identifier Source: org_study_id