Simvastatin and Emotional Processing (OxSTEP) (OxSTEP)

  • STATUS
    Recruiting
  • End date
    Jul 5, 2023
  • participants needed
    100
  • sponsor
    University of Oxford
Updated on 4 October 2022
body mass index
depression
depressed mood
hmg-coa reductase inhibitors
Accepts healthy volunteers

Summary

Simvastatin is being employed because it is a 'statin'. As a drug class, statins have broad anti-inflammatory properties. Low-level inflammation is thought to be a potentially important mediator of the effects of psychosocial stress (including loneliness) on affect and vulnerability to depression. In this study we are using statins as an experimental tool to investigate this relationship further. Statins are widely prescribed agents that are regarded as very safe and so are suitable tools in this context. We have selected simvastatin because it is one of the most widely used statins and has an excellent safety profile, being also available 'over the counter'.

Description

Depression is common and associated with considerable disability (James-2018). Furthermore, the impact of the current Covid-19 pandemic on the mental health of the general population, especially in terms of depression, anxiety, and stress is proving enormous (Vindegaard-2020). Such effect is likely due to an intricate combination of biological factors (potentially neuroimmune [Troyer-2020]) as well as psychosocial aspects (such as self-isolation and loneliness [Blanco-2020]) - the latter significantly associated with worse mental health outcomes (Leigh-Hunt-2017). In particular, an important factor associated with increased vulnerability to depression is social isolation and loneliness, both of which are exacerbated by the measures needed to control the Covid-19 pandemic. Within this context, there is a need to identify factors that may be protective against the negative mental health consequences of such psychosocial stressors.

There is increasing evidence that low-level inflammation is an important mechanism by which psychosocial stress, including loneliness, predisposes to depressive symptomatology (Nersesian-2018). Consistent with this, a recent observational study conducted by our group in the context of the COVID-19 pandemic found that people who were taking a statin (which have broad anti-inflammatory properties) had a relatively increased positive bias on measures of emotional processing that are known to be associated with psychological vulnerability to depression (COSIE study, R69299/RE001). This raises the interesting possibility that reduced levels of inflammation have a protective effect within the current context of the high levels of psychosocial stress associated with the pandemic. This is consistent with a wealth of epidemiological studies showing that, at a population level, prescription of statins is associated with decreased rates of anxiety and depression (Parsaik-2014).

The aim of the current study is to extend these observational studies and experimentally test in a prospective double-blind controlled design whether reducing inflammation by administering a statin lowers vulnerability to depression in at-risk individuals, as measured by well-established cognitive biomarkers.

Patients with depression and people vulnerable to depression consistently show negative biases in emotional processing, which are believed to play a key role in the development and maintenance of clinical depressive symptoms (Roiser-2013). Overall, evidence suggests that early changes in emotional processing can serve as valid surrogate markers of antidepressant efficacy (Harmer-2017). Intriguingly, our previous study showed that patients on statins were less likely to show negative cognitive biases (COSIE study, R69299/RE001): this observation provides a potential cognitive biomarker of the ability of statins to prevent depression. We and others have also shown that induction of inflammation in healthy participants is associated with negative cognitive biases and deficits in reward learning (Cooper-2017; Miller-2017). In addition, inflammation is associated with impairment in tests of learning and memory (Gorelick-2010). This could add to the likelihood of inflammation leading to depression through compromise of problem-solving skills.

While the COSIE study suggests that statin treatment is associated with decreased negative emotional processing in an at-risk population, such observational studies are subject to confounders and require prospective controlled investigations for confirmation. In the present study therefore we propose to assess the effect of 28-days administration of statin treatment compared to placebo on emotional processing, reward learning, and working memory, in 100 healthy volunteers at-risk for depression due to loneliness in the context of the Covid-19 pandemic. We will also measure waking salivary cortisol as an index of the effect of inflammation to activate the hypothalamic-pituitary-adrenal (HPA) axis. The statin we have selected is simvastatin in view of its widespread use and safety. Our prediction is that, relative to placebo, in this at-risk group, simvastatin will lead to positive effects on emotional processing, reward learning, working memory, and will also lower waking salivary cortisol.

Details
Condition Depression, Inflammation
Treatment Placebo, Simvastatin 20mg
Clinical Study IdentifierNCT04973800
SponsorUniversity of Oxford
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Male or female
Age 21-65 years
At-risk for depression as measured by a score >6 on the UCLA 3-item Loneliness Scale
Body Mass Index in the range of 18-30
Willing and able to give informed consent for participation in the study
Registered with a GP and consenting to GP being informed of participation in the study
Currently living in the UK and sufficiently fluent English to understand and complete the tasks
Able to access and use a computer with Internet
Able to complete online questionnaires and tasks

Exclusion Criteria

Currently on any regular prescribed medications (except the contraceptive pill), unless unlikely to compromise safety or affect data quality in the opinion of the Investigator
History or current significant psychiatric illness (other than past [>6 months] episodes of depression or anxiety)
Current alcohol or substance misuse disorder (< 6 months)
History of, or current significant hepatic disease
History of, or current significant neurological condition (e.g. epilepsy)
History of haemorrhagic stroke or deep brain structures stroke
Known hyperglycaemia/pre-diabetes
Known hypersensitivity to the study drug (i.e. simvastatin) or sucrose
Pregnant, breast feeding, women of child-bearing potential not using appropriate contraceptive measures
Participation in a study that uses the same or similar computer tasks (apart from the N-back) as those used in the present study
Participation in a study that involves the use of a medication within the last 3 months
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note