MICA:Translational validation of 5HT7 antagonists for the treatment of cognitive impairment in bipolar disorder: a proof of concept neuroimaging study

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Bipolar disorder is a serious mental health problem in which people experience repeated episodes of depression and elated mood. Bipolar disorder affects around 1.2 million people in the UK and costs around £5.2 billion per year. Around 60% of people with bipolar disorder experience problems with their attention and memory, known as cognitive impairment, which greatly affects the ability to work and hold relationships. Currently there are no effective drug treatments for cognitive impairment experienced by people with bipolar disorder. However, drugs which block a type of brain chemical receptor, called the 5HT7 receptor, may be a promising new treatment. The main aim of this study is to understand the effect of a medication called JNJ-18038683, which specifically blocks the 5HT7 receptor, on brain activity and cognitive performance. We will examine the effect of JNJ-18038683 in people with bipolar disorder who show evidence of cognitive impairment and also in healthy people. We plan to do this to determine whether JNJ-18038683 affects brain activity which occurs whilst performing attention and memory tasks, and whether JNJ-18038683 corrects impairments in brain activity and cognitive performance. We plan to recruit 34 people with bipolar disorder and 34 healthy people to take part in the study. Each person taking part in the study will be carefully screened for suitability and will then complete tests of attention and memory function which measures cognitive performance. They will then take 10mg JNJ-18038683 for one week and will be switched to placebo for one week, or vice versa, after a two-week drug free period. Some participants will take JNJ-18038683 first and some will take placebo first, and neither participants nor the staff running the study will know which medication has been taken. We will study the effects of JNJ-18038683 and placebo on brain activity and cognitive performance on day 7 of each treatment period. Brain activity will be measured using a brain scan called magnetic resonance imaging (MRI) which produces very detailed images of the structure and function of the brain. We will examine how JNJ-18038683 and placebo affects the levels of brain activity during the MRI scan by asking participants to complete thinking and mood tasks in the scanner and then analysing the level of brain activity this produces. We plan to assess whether JNJ-18038683 changes brain activity produced during these tasks, and in people with bipolar disorder whether JNJ-18038683 normalises brain activity, by comparing brain activity levels on day 7 of JNJ-18038683 and placebo treatments. We will also assess whether JNJ-18038683 improves cognitive performance by comparing memory and attention test results on day 7 of JNJ-18038683 and placebo treatments. We hope that these results will support the development of further large clinical treatment studies. When the study is complete we will publish its results in scientific journals and communicate this to people with bipolar disorder, mental health professionals and to the general public through press briefings and social media. Overall, we anticipate that this study will allow us to better understand the potential of 5HT7 blockers such as JNJ-18038683 for the treatment of cognitive impairment in people with bipolar disorder which we hope will lead to the development of new treatments.