Ketamine-ECT Study
| ISRCTN | ISRCTN14689382 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14689382 |
| EudraCT/CTIS number | 2011-005476-41 |
| Secondary identifying numbers | 12141 |
- Submission date
- 25/07/2012
- Registration date
- 30/07/2012
- Last edited
- 07/04/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Mental and Behavioural Disorders
Plain English Summary
Background and study aims
Depression is a major cause of disability with many patients failing to recover with current drug and psychological treatments. Electroconvulsive Therapy (ECT), the most effective treatment known for severe depression, can be life-saving but remains controversial. The most serious concerns are problems with memory and other cognitive (thinking) abilities. This can lead to patients stopping ECT before it has improved their mood, and many people report distressing long-term loss of past memories. If these memory and cognitive effects could be prevented, and fewer ECT treatments were needed, this would represent an important advance and would change clinical practice. Ketamine is an anaesthetic drug that blocks the effects of a major brain chemical, glutamate, involved in memory and mood. Preliminary research has found that ketamine protects against the adverse effects of ECT on memory and makes it work more quickly. The proposed study will investigate the benefit of adding ketamine to the usual anaesthetic used for ECT. It will involve enough patients receiving ECT in an NHS setting to be able to assess whether it would be a useful routine treatment.
Who can participate?
160 patients due to receive ECT in 5 NHS Trusts in the North of England, who give informed consent. The 5 trusts are: Manchester Mental Health & Social Care Trust, Northumberland, Tyne & Wear NHS Foundation Trust, Leeds & York Partnership NHS Foundation Trust, Greater Manchester West Mental Health NHS Foundation Trust and Pennine Care NHS Foundation Trust.
What does the study involve?
Patients will be randomised to either receive ketamine injection or saline dummy (placebo) during ECT. The effects of the treatment will be assessed using validated measures of memory, cognitive function and mood improvement during and at the end of treatment, and one and four months after treatment. In depression there are changes in nerve cell connections (neural networks) between brain areas responsible for mood and cognitive function; glutamate is involved in these. We will use brain imaging to investigate whether ketamine a) prevents the ECT-induced impaired working of the front part of the brain (frontal cortex) believed to contribute to cognitive adverse effects, and b) reduces disruption in connections between the frontal cortex and an important memory area of the brain (hippocampus). Given the difficulty in studying severely ill people we will use magnetic resonance imaging (MRI) in a small subgroup to look at the network connections and brain glutamate levels. We will relate this to results obtained in a majority of patients from a simple, portable, imaging technology, near infrared spectroscopy (NIRS).
What are the possible benefits and risks of participating?
The main possible benefit from taking part is that patients who do get ketamine may have less difficulty with their memory or cognition following ECT than they might have had otherwise. In addition they may also improve more quickly and therefore need fewer ECT treatments to get well. The effects of ECT on patients' mood and memory will be carefully assessed, which may help them and their clinical team plan their care. Also, people who take part in studies like this can get benefit just from taking part. Patients will not know whether they will receive ketamine or not, but, if the study is successful and ketamine is helpful in improving the outcome of ECT treatment, it may help patients in the future. The main risk is due to the fact that both ketamine and ECT increase blood pressure. However, we will not recruit anyone into the study who has heart problems, uncontrolled blood pressure or raised pressure in the head, as well as some other conditions that might increase risks (such as liver damage). Otherwise the risks are the same as for ECT itself and of having a brief anaesthetic. This means that patients having ECT as an outpatient will need to be fully recovered from the anaesthetic and the effects of ECT before leaving hospital.
Where is the study run from?
Neuroscience and Psychiatry Unit, University of Manchester (UK)
When is the study starting and how long is it expected to run for?
September 2012 to August 2014
Who is funding the study?
NIHR Efficacy and Mechanism Evaluation (UK)
Who is the main contact?
Ms Jo Lowe
jo.e.lowe@manchester.ac.uk
Contact information
Scientific
University of Manchester
Neuroscience and Psychiatry Unit
Stopford Building
Oxford Road
Manchester
M13 9PT
United Kingdom
| jo.e.lowe@manchester.ac.uk |
Study information
| Study design | Randomised interventional phase IV trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Ketamine augmentation of electroconvulsive therapy to improve outcomes in depression |
| Study hypothesis | That the addition of ketamine at a sub-anaesthetic dose (versus placebo) to the usual anaesthetic for electroconvulsive therapy (ECT) given for depression will prevent adverse cognitive effects of ECT and speed the improvement in depressive symptoms. |
| Ethics approval(s) | First MREC, 25/01/2012, ref: 12/NW/0021 |
| Condition | Bipolar affective disorder, depression |
| Intervention | Ketamine, 0.5mg/kg or 0.9% sodium chloride given with the anesthetic induction agent at each ECT treatment session; Study Entry : Single Randomisation only |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Ketamine |
| Primary outcome measure | Change in memory measured at baseline and end of ECT course |
| Secondary outcome measures | 1. Changes in memory measured at baseline and one and 4 month follow up 2. Cognitive changes measured at baseline and a end of ECT, and one and 4 month follow up 3. Evaluation of Memory (GSEMy) symptoms ratings measured at baseline, after 4 ECT treatments, at end of ECT and at one and 4 month follow up |
| Overall study start date | 01/09/2012 |
| Overall study end date | 31/08/2014 |
Eligibility
| Participant type(s) | Mixed |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 160; UK Sample Size: 160 |
| Participant inclusion criteria | Patients: 1. Only patients who are referred by their consultant for ECT and who are patients of one of the following 5 participating Trusts will be able to take part: Manchester Mental Health & Social Care Trust, Northumberland, Tyne & Wear NHS Foundation Trust, Leeds & York Partnership NHS Foundation Trust, Greater Manchester West Mental Health NHS Foundation Trust and Pennine Care NHS Foundation Trust (added as of 13/11/2012) 2. Male or female aged 18 years and above 3. Current DSM-IV diagnosis of a major depressive episode, moderate or severe as part of unipolar or bipolar disorder mood disorder diagnosed by the Mini International Neuropsychiatric Interview (MINI) 4. American Society of Anaesthesiologists (ASA) score (excluding mental health considerations in the scoring) of 1, 2 or stable 3, and judged as suitable to receive ketamine by an anaesthetist 5. Verbal IQ = 85, sufficiently fluent in English to validly complete neuropsychological testing 6. Capacity to give informed consent 7. Willing to undertake neuropsychological testing as part of the study. Healthy control: 1. Aged 18 years or more 2. Currently psychiatrically well, confirmed through MINI interview and no current psychotropic medication 3. In good physical health 4. Male or female participants 5. Aged 18 years and above |
| Participant exclusion criteria | Patients: 1. DSM-IV diagnosis of a primary psychotic or schizoaffective disorder, current primary obsessive compulsive disorder or anorexia nervosa 2. History of drug or alcohol dependence (DSM-IV criteria) within the last year 3. ECT in last 6 months (to avoid confounding the assessment of cognitive outcomes) or has previously received ECT in the current trial 4. Known hypersensitivity or contraindication to ketamine or excipients in the injection; including significant cardiovascular disease, uncontrolled hypertension, glaucoma, cirrhosis or significant liver impairment 5. Known hypersensitivity or contraindication to concomitant medications used for ECT: thiopentone (thiopental), propofol and suxamethonium or excipients in the injections 6. Evidence of organic brain disease including dementia, neurological illness or injury, or medical illness which may significantly affect neuropsychological function 7. Detained under the Mental Health Act (1983 as amended 2007) or unable to give informed consent 8. Pregnancy, or at risk of pregnancy and not taking adequate contraception, breastfeeding 9. Score = 24 on the Mini Mental State Examination (MMSE) 10. In the subgroup receiving MRI based investigation (fMRI, MRS and ASL) contraindication to MRI (eg metal implants or foreign bodies such as from a surgical implant, accident or injury). Control: 1. Personal history of psychiatric disorder, as revealed by MINI interview 2. First degree family history of major psychiatric illness requiring treatment 3. Significant physical illness including organic brain disease, neurological illness or injury that could interfere with interpretation of results 4. Psychotropic medication or other medication that could interfere with interpretation of results 5. Score = 24 on the Mini Mental State Examination (MMSE) 6. In the subgroup receiving MRI based investigation (fMRI, MRS and ASL) contraindication to MRI (eg metal implants or foreign bodies such as from a surgical implant, accident or injury). |
| Recruitment start date | 01/09/2012 |
| Recruitment end date | 31/08/2014 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
M13 9PT
United Kingdom
Sponsor information
Hospital/treatment centre
Rawnsley Building
Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
England
United Kingdom
| Website | http://www.mhsc.nhs.uk/ |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Efficacy and Mechanism Evaluation Programme, EME
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 21/10/2015 | Yes | No | |
| Results article | results | 01/03/2017 | Yes | No | |
| Results article | results | 01/05/2017 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
07/04/2017: Publication reference added.
03/04/2017: Publication reference added.
