Healthy VolunteersPhase 4Schiz_2NCT01140620

Effects of Ketamine and Risperidone on Cognition

A Phase 4 study testing ketamine, risperidone and saline in people with Healthy Volunteers and Schizophrenia, run by University of Manchester at 3 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers, Schizophrenia
What is being tested?: ketamine, risperidone and saline
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 87 participants
Where: 3 sitesUnited Kingdom
Study dates: Jun 2010to Dec 2010
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

Show all 21Show fewer

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.

Who cannot join

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.

Show all 21Show fewer

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.

Trial locations and contacts

3 sites in 1 country.

United Kingdom3 sites

School of Psychology, University of Cardiff
Cardiff, CF10 3AT
Institute of Psychiatry, King's College London
London, Greater London, SE5 8AF
University of Manchester (Dept of Neuropyschiatry)
Manchester, Manchester, M13 9PT

Other trials in United Kingdom

About this study

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

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.

Read the 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.

Conditions: Healthy Volunteers, Schizophrenia
Being tested: ketamine, risperidone, saline, placebo risperidone
Keywords: NMDA receptor antagonism, cognitive processes, healthy volunteers, dopamine antagonist, schizophrenia
Medical subject headings: Schizophrenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ketamineDrug
Also called ketalar
ketamine infusion to achieve plasma concentrations of 100 ng/mL. Duration approximately 3 hours
risperidoneDrug
Also called risperdal
risperidone (2 mg) capsule. One dosing of 2 mg.
salineDrug
saline infusion. Duration approximately 3 hours
placebo risperidoneDrug
Also called placebo risperdal
placebo capsule to match risperidone 2 mg capsule

Study groups in NCT01140620
Study group	Role	What they receive
ketamine and risperidone	Experimental	Oral risperidone pretreatment and intravenous ketamine infusion Receives: Drug: ketamine; Drug: risperidone
ketamine and placebo	Active comparator	Oral placebo risperidone pretreatment and intravenous ketamine infusion Receives: Drug: ketamine; Drug: placebo risperidone
saline and risperidone	Active comparator	Oral risperidone pretreatment and intravenous saline infusion Receives: Drug: risperidone; Drug: saline
saline and placebo	Placebo comparator	Oral placebo risperidone pretreatment and intravenous saline infusion Receives: Drug: saline; Drug: placebo risperidone
Patients with Schizophrenia	No intervention	Patients with schizophrenia will not receive study drug and will not undergo randomisation.

What is being measured

The primary outcome is the main question the study is designed to answer.

Biconditional learning task
Accuracy (% correct) for simple and biconditional learning trials, averaged over 8 blocks
Measured: 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.
Measured: 6 months
Salience Attribution task
1. Implicit aberrant salience (ms).
2. i. Overall reaction time b.ii. Implicit adaptive salience (ms).
3. Explicit adaptive salience (mm).
4. Explicit aberrant salience (mm).
5. Commission errors.
6. Omission errors.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: 6 months
Questionnaires and assessment scale scores
1. CADSS.
2. BPRS.
3. Effects of Drug Rating Scale.
Measured: 6 months

Secondary outcomes (1)

Pharmacogenomic analysis
An exploratory genetic analysis aiming to correlate any genetic polymorphisms associated with schizotypy, schizophrenia or brain development with study outcomes.
Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2010Dec 2010

First posted9 Jun 2010 (estimated)
Study startJun 2010
Primary completionNov 2010
Study completionDec 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Healthy VolunteersStudies of the same condition, open and under way.
More trials run by University of ManchesterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 87 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01140620
Sponsor's protocol ID: P1V-SCH-CT02-09
Acronym: Schiz_2
Status last verified: Nov 2016
First submitted: 8 Jun 2010
Last updated: 9 Nov 2016
Results posted: No
Data monitoring committee: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Not yet recruitingObservational study
Establishment of Biobank of Nasal Epithelium Samples From Healthy Volunteers
Healthy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
Not yet recruitingObservational study
Screening Protocol
Pain

All Healthy Volunteers trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01140620
Acronym / sponsor ID: Schiz_2 / P1V-SCH-CT02-09
Conditions: Healthy Volunteers, Schizophrenia
Keywords: NMDA receptor antagonism, cognitive processes, healthy volunteers, dopamine antagonist, schizophrenia
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 87 participants (actual)
Lead sponsor: University of ManchesterUniversity, hospital or other
Collaborators: Cardiff University, King's College London, P1vital Limited
Study start: Jun 2010
Primary completion: Nov 2010 (actual)
Study completion: Dec 2010 (actual)
First posted: 9 Jun 2010 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 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 study will provide information about the sensitivity of the biomarker tasks in detecting the effects of the pharmacological treatments for schizophrenia in healthy volunteers.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
ketamine and risperidone	Experimental	Drug: ketamine, Drug: risperidoneOral risperidone pretreatment and intravenous ketamine infusion
ketamine and placebo	Active comparator	Drug: ketamine, Drug: placebo risperidoneOral placebo risperidone pretreatment and intravenous ketamine infusion
saline and risperidone	Active comparator	Drug: risperidone, Drug: salineOral risperidone pretreatment and intravenous saline infusion
saline and placebo	Placebo comparator	Drug: saline, Drug: placebo risperidoneOral placebo risperidone pretreatment and intravenous saline infusion
Patients with Schizophrenia	No intervention	–Patients with schizophrenia will not receive study drug and will not undergo randomisation.

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (21 listed)

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.

Key exclusion criteria (21 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ketamineAlso: ketalarketamine infusion to achieve plasma concentrations of 100 ng/mL. Duration approximately 3 hours	Drug	ketamine and placebo, ketamine and risperidone
risperidoneAlso: risperdalrisperidone (2 mg) capsule. One dosing of 2 mg.	Drug	ketamine and risperidone, saline and risperidone
salinesaline infusion. Duration approximately 3 hours	Drug	saline and placebo, saline and risperidone
placebo risperidoneAlso: placebo risperdalplacebo capsule to match risperidone 2 mg capsule	Drug	ketamine and placebo, saline and placebo

Primary outcome

Biconditional learning task
Time frame: 6 months
Accuracy (% correct) for simple and biconditional learning trials, averaged over 8 blocks
Eye movement task
Time frame: 6 months
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.
Salience Attribution task
Time frame: 6 months
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.
Signal detection task
Time frame: 6 months
1. d׳ value 2. Hits, when participants respond positively and a voice is present. 3. False alarm rate. 4. β value.
N-Back
Time frame: 6 months
1. Correct responses across three levels of difficulty. 2. Percentage of overall responses that was correct. 3. Errors of omission. 4. Errors of commission.
Spatial working memory
Time frame: 6 months
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
Verbal Fluency
Time frame: 6 months
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.
Event-related potentials (Manchester EEG pilot study only)
Time frame: 6 months
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
Questionnaires and assessment scale scores
Time frame: 6 months
1. CADSS. 2. BPRS. 3. Effects of Drug Rating Scale.

1 secondary outcome

Pharmacogenomic analysis
Time frame: 12 months

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2016.
websiteLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Healthy Volunteers

Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Not yet recruitingObservational study
Establishment of Biobank of Nasal Epithelium Samples From Healthy Volunteers
Healthy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
Not yet recruitingObservational study
Screening Protocol
Pain

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Professor Bill Deakin principal investigator

University of Manchester

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing ketamine, risperidone and saline in people with Healthy Volunteers and Schizophrenia, run by University of Manchester at 3 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Biconditional learning task (time frame: 6 months). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01140620.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2016.