Effects of Ketamine and Risperidone on Cognition
Condition: Healthy Volunteers; Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      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.
    

Intervention name(s): ketamine; risperidone; saline; placebo risperidone
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): ketamine infusion to achieve plasma concentrations of 100 ng/mL. Duration approximately 3 hours; risperidone (2 mg) capsule. One dosing of 2 mg.; saline infusion. Duration approximately 3 hours; placebo capsule to match risperidone 2 mg capsule
Other intervention name(s): ketalar; risperdal; placebo risperdal
Intervention MeSH terms: Ketamine; Risperidone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: NMDA receptor antagonism; cognitive processes; healthy volunteers; dopamine antagonist; schizophrenia