TIDE: Tofacitinib in depression, v1.3
Research type
Research Study
Full title
The effects of the anti-inflammatory drug, tofacitinib on emotional and reward processing in patients with treatment-resistant depression and elevated high-sensitivity C-reactive protein
IRAS ID
258096
Contact name
Philip J Cowen
Contact email
Sponsor organisation
University of Oxford / Clinical Trials and Research Governance
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 11 months, 28 days
Research summary
Summary of Research
Treatment-resistant depression (TRD) is common and disabling. There is growing evidence that resistance to treatment may be due to an underlying inflammatory condition in a subgroup of depressed patients. The development of novel anti-inflammatory agents for immunological disorders offers the opportunity of trialling these drugs for TRD. Prior to a formal clinical trial it is helpful to assess whether anti-inflammatory drugs may produce evidence of potential clinical antidepressant effects by using 'experimental medicine' biomarkers.In this study, we will recruit 50 patients with TRD and elevated high-sensitivity C-reactive protein (a marker of inflammation). The purpose of this study is to investigate the effect of tofacitinib (a small-molecule that reduces inflammation by inhibiting the Janus Kinase pathway) on their emotional and reward processing (early markers that predict response to antidepressants).
The study will involve 3 visits in total, all taking place at the Warneford Hospital in Oxford. We will randomly assign participants to receive 7 days of treatment with either tofacitinib or a placebo (a dummy tablet). Neither the participants nor the researchers will know who has been assigned to each tablet. Once the study period is finished, the study treatment will be discontinued.
We will use computerised tasks (the Facial Expression Recognition and the Emotional Recall tasks); we hypothesise that, relative to placebo, tofacitinib will increase the perception of positive facial expressions and the memory of positive words describing oneself. Moreover, we will use fMRI at resting state and during similar emotional and reward processing tasks to assess neural responses in specific brain areas linking depression and inflammation.
Positive results from this study may lead to formal clinical trials of tofacitinib in patients with TRD with evidence of elevated inflammation.
The funding bodies include the Wellcome Trust and the Medical Research Council.
Summary of Results
The effects of the anti-inflammatory drug, tofacitinib on emotional and reward processing in patients with treatment-resistant depression and elevated high-sensitivity C-reactive proteinThis study aimed to investigate whether an anti-inflammatory drug changes how the brain deals with emotional and reward information in people with depression. There is growing scientific evidence that some people do not respond to conventional antidepressants because they have concomitant inflammation and so may benefit from taking anti-inflammatory drugs. Our research has previously shown that antidepressants affect how people experience certain kinds of information, for example by making them focus on positive facial expressions more than negative ones. These effects on ‘emotional processing’ can be found very early on in treatment, even before a patient ‘feels better’. We can measure these early changes and use this information to predict whether the treatment will actually help people feel better in the long term.
The drug we were investigating is called tofacitinib. It is currently licensed for treating inflammatory disorders such as rheumatoid arthritis, and it has been shown to be acceptably safe and well-tolerated in these patients. In the current study we wanted to test whether tofacitinib can change emotional processing in the same way as standard antidepressant drugs.
This study began in January 2020. Initial telephone screenings for participant suitability were carried out for 45 people. A large proportion of those telephone screened were unsuitable to take forward in the study due to various exclusion factors, resulting in only 6 participants going on to have an on-site screening visit. This screening visit involved a number of psychological and physical measures. Following this, two participants fulfilled the inclusion criteria. One of these participants took the full course of tofacitinib and completed the study. The other participants had to stop the study (March 2020) due to the Covid-19 pandemic. The Covid-19 pandemic caused this study to be suspended due to national lockdown and concerns about using an immunomodulatory drug in the face of a new virus. Even though the current Covid situation has improved in terms of national restrictions and the availability of a vaccine, it was felt that it would be unethical to restart this study using the current study drug whilst Covid-19, and variants thereof, are still newly circulating. Thus, the study was permanently terminated in May 2022.No study results can be reported due to this early termination of the study.
REC name
South Central - Oxford B Research Ethics Committee
REC reference
19/SC/0136
Date of REC Opinion
23 Apr 2019
REC opinion
Favourable Opinion