Synaptic imaging & network activity in treatment resistant depression
Research type
Research Study
Full title
Synaptic ImaGing and Network Activity in Treatment Resistant dEpression (SIGNATuRE)
IRAS ID
297200
Contact name
Mitul Mehta
Contact email
Sponsor organisation
Kings College London
Clinicaltrials.gov Identifier
To be confirmed once registered, The Open Science Framework [OSF.io]
Duration of Study in the UK
1 years, 5 months, 31 days
Research summary
Depression is one of the most common health conditions worldwide and can have a severe impact on an individual’s ability to function and their quality of life. People with Major Depressive Disorder (MDD) have a persistent low mood, loss of motivation, and experience reduced pleasure from previously enjoyable activities. Depressive symptoms are also a key feature of Bipolar disorder, in which periods of depression alternate with periods of abnormally elevated mood. Changes in brain anatomy, metabolism, connectivity and function have been shown to be present in patients with depression.
While drug treatments and psychological therapies exist for depression, around 30% of patients fail to successfully respond to any of these treatments. When patients fail to respond to two or more treatments, this is often called treatment resistant depression, or TRD. However, recent research has suggested that some medications which are usually prescribed for other purposes may also have benefits for treating the symptoms of depression. Ketamine, a widely used anaesthetic, has recently emerged as an effective, rapid acting antidepressant with promising effects in treatment resistant depression.
In this study we will use brain imaging techniques (MRI and EEG) to see how brain activation patterns change when people with depression have taken the treatment, and how this relates to any changes in their symptoms. This will help us understand more about the illness itself and how we might be able to treat it better. It will also help us to further develop a combination of fMRI and EEG as biomarkers which can be used in the development of future treatments.
This study is a placebo-controlled, double-blind, cross-over study. We will recruit 50 patients with MDD who will attend for 11 study visits. The first is a screening visit followed by a baseline study day where they will have an MRI scan and EEG scan. We will assess their memory, concentration and mood using tasks and questionnaires and take blood samples for measurement of proteins and hormones. There are 2 study periods, each comprising of 3 treatment infusion visits, 3-5 days apart and a post treatment study day on the day after the 3rd infusion visit. Infusion visits comprise of a 40-minute study medication infusion and completion of mood and symptom questionnaires. The post treatment study day will consist of an MRI scan and an EEG scan, tasks and questionnaires and blood samples for measurement of proteins, hormones and study medication levels. There will be minimum of 8 days between the first post treatment study day and the start of the second treatment period. Their final follow up study day will be at least 8 days after the second post treatment study day. During this visit they will complete tasks and questionnaires and have a final blood sample. During the intervals between the treatment periods and the follow up study day, participants will be asked to complete a computerised task at home to assess their learning.
Participants will be randomised to receive three 40-minute infusions of ketamine 0.5mg/kg during one treatment period and three 40-minute infusions of midazolam 0.045mg/kg during the other. Midazolam is commonly used as an active placebo in ketamine studies as it can mimic the effects of ketamine (sedation and disorientation).REC name
London - City & East Research Ethics Committee
REC reference
21/LO/0493
Date of REC Opinion
15 Jul 2021
REC opinion
Favourable Opinion