HealthyNCT03966859
7-day Atorvastatin and Emotional Processing
A study testing Atorvastatin 20mg in people with Healthy, run by University of Oxford at 1 site in United Kingdom.
Trial summary
Work in our group has revealed that short-term (7-day) administration of antidepressants produces positive biases in the processing of emotional information in healthy volunteers. Such effect might be an important neuropsychological mechanism of antidepressant action. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Atorvastatin 20mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 19 Jun 2019to 1 Feb 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female
- Aged 18-50 years
- Sufficiently fluent English to understand and complete the tasks
- Body Mass Index in the range of 18-30
- Participant is willing and able to give informed consent for participation in the study
- Not currently taking any regular medications (except the contraceptive pill)
Who cannot join
- Currently any regular medications (except the contraceptive pill)
- History or current significant psychiatric illness
- Current alcohol or substance misuse disorder
- History or current significant hepatic disease
- History or current significant neurological condition (e.g. epilepsy)
- Known hypersensitivity to the study drug (i.e. atorvastatin)
Show all 9Show fewer
- 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 as those used in the present study
- Participation in a study that involves the use of a medication within the last three months
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Seven-Day Atorvastatin Administration on Emotional Processing, Reward Processing, and Inflammation in Healthy Volunteers
Work in our group has revealed that short-term (7-day) administration of antidepressants produces positive biases in the processing of emotional information in healthy volunteers. Such effect might be an important neuropsychological mechanism of antidepressant action.
The current study will investigate the effect of seven-day administration of atorvastatin 20mg on emotional and reward processing tasks in healthy volunteers. There is evidence that statins may exert antidepressant effects via anti-inflammatory and anti-oxidant pathways, and it is therefore predicted that atorvastatin will have positive effects on emotional and reward processing.
Read the detailed description
Depression is common and associated with considerable health disability. Traditional antidepressants mainly work by modulating monoamine levels in the synaptic cleft; however, the evidence that depression is caused by impaired serotonin or noradrenaline activity is weak and inconsistent, and indeed current antidepressant strategies remain burdened by partial efficacy, poor side-effects profile, and a slow onset of therapeutic action. Therefore, there is a pressing need to develop antidepressant medications with novel non-monoaminergic mechanisms of action - or, conversely, to identify alternative pathophysiological pathways leading to depression that can be targeted with new drugs. Intriguingly, there is growing evidence that both peripheral and central inflammation play a role in the pathophysiology of depression.
Patients with depression consistently show negative biases in emotional processing, which are believed to play a key role in the aetiology and maintenance of their clinical symptoms. Overall, robust evidence suggests that early changes in emotional processing can serve as valid surrogate markers of antidepressant efficacy; for example, seven days' treatment with selective serotonin and noradrenaline reuptake inhibitors (citalopram and reboxetine respectively) compared to placebo decreases the recognition of negative facial expressions and recall of negative versus positive stimuli in healthy volunteers. Conversely, another study using the pro-inflammatory cytokine interferon-α showed that inflammatory-mediated depression can be associated with an increased recognition of negative facial expressions. Furthermore, depression associated with inflammation is characterised by significant symptoms of anhedonia, which has been linked to diminished neural responses to reward anticipation. Such reward-deficit is particularly refractory to conventional serotoninergic and noradrenergic antidepressants, and even the antidepressant bupropion (a noradrenaline and dopamine reuptake inhibitor), whilst inducing positive changes in emotional processing, appears to worsen reward processing. However, the reversal of this deficit in reward processing is still considered as a valuable marker of target engagement for anti-inflammatory drugs in depression, as a more sensitive outcome measure than traditional rating scales designed to capture the global clinical symptomatology.
The 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors or statins are recommended and have been widely used since the '80s for the primary and secondary prevention of cardiovascular diseases. It is now established that these medications have significant anti-inflammatory effects that are independent from their lipid-lowering properties, as well as appearing early in treatment only after seven day of administration. Statins are considered extremely safe drugs: their more common side-effect are muscle pain or weakness (usually mild and quickly responding to stopping or switching medication) and elevation of liver transaminases (significant only in case of pre-existing hepatic disease), whereas more serious adverse events include rhabdomyolysis (very rare but severe myopathy associated with elevated creatine kinase and myoglobinuria), new-onset diabetes mellitus (in predisposed individual with pre-existing hyperglycaemia), and haemorrhagic stroke (in patients with prior haemorrhagic stroke or lacunar infarct); however, clinical trials have ultimately concluded that such adverse events attributed to statin therapy in routine practice are not actually caused by it, especially at doses lower than 80mg/day and when used for less than 52 weeks. Other common (≥ 1/100, < 1/10) but usually mild side-effects include: nasopharyngitis, pharyngo-laryngeal pain, epistaxis, headache, and gastrointestinal disturbances (constipation, diarrhoea, flatulence, dyspepsia, nausea). Importantly, a potential antidepressant effect for statins has been confirmed in animals, as well as clinically in observational and interventional studies. Although their anti-inflammatory and anti-oxidant properties have been involved, the mechanisms underlying the antidepressant effects of statins remain unclear, therefore further translational studies have been advocated in order to elucidate this aspect.
In this exploratory study, we will investigate the effect of seven-day administration of atorvastatin 20mg once daily compared to placebo on emotional and reward processing tasks in 50 healthy volunteers. In view of the previous evidence that statins may exert antidepressant effects via anti-inflammatory and anti-oxidant pathways, we predict that atorvastatin will have positive effect on emotional and reward processing.
- Conditions
- Healthy
- Being tested
- Atorvastatin 20mg, Lactose placebo
- Keywords
- Atorvastatin, Emotional processing, Reward processing, Inflammation (C-Reactive Protein)
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atorvastatin 20mgDrug
Also called Lipitor, Atorva
oral dose, once daily for 7 days
Lactose placeboOther
Also called placebo
oral dose, once daily for 7 days
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants will receive lactose placebo tablets, encapsulated in opaque capsules, and will be asked to take one capsule daily for seven days at night-time, by mouth Receives: Other: Lactose placebo |
| Atorvastatin | Experimental | Participants will receive 20mg atorvastatin tablets, encapsulated in opaque capsules, and will be asked to take one capsule daily for seven days at night-time, by mouth Receives: Drug: Atorvastatin 20mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Accuracy and reaction times during facial expression recognition task
Faces representing varying degrees [from "neutral" (0%) to "full prototypical emotion" (100%) of basic emotions (happiness, fear, anger, disgust, sadness, surprise)] are displayed on the screen and participants are asked to quickly and correctly classify them. Accuracy and reaction times on positive vs negative stimuli are compared between those receiving drug and placebo.
Measured: Assessed during the research visit after the seventh day of atorvastatin or placebo administration, i.e. on the eight day after the patient started taking atorvastatin or placebo
Accuracy and reaction times during faces dot-probe task
Faces acting as positive or negative emotional stimuli (happy or fearful facial expressions) are presented together with a matched neutral face. One is presented above and one below a central fixation point. Subsequently, a probe appears behind one of the two faces and participants are asked to quickly indicate the position of the probe. Accuracy and reaction times on positive vs negative stimuli are compared between those receiving drug and placebo.
Measured: Assessed during the research visit after the seventh day of atorvastatin or placebo administration, i.e. on the eight day after the patient started taking atorvastatin or placebo
Accuracy and reaction times during emotional categorisation task
Words describing positive and negative personality characteristics are presented, and participants are asked to quickly indicate whether they would like or dislike being described with the presented word. Accuracy and reaction times on positive vs negative stimuli are compared between those receiving drug and placebo.
Measured: Assessed during the research visit after the seventh day of atorvastatin or placebo administration, i.e. on the eight day after the patient started taking atorvastatin or placebo
Accuracy during emotional recall task
After a delay from the Emotional categorisation task, participants are asked to recall and write down as many words as possible from it. Accuracy in recall of positive vs negative stimuli are compared between those receiving drug and placebo.
Measured: Assessed during the research visit after the seventh day of atorvastatin or placebo administration, i.e. on the eight day after the patient started taking atorvastatin or placebo
Accuracy and reaction times during emotional recognition memory task
The original personality descriptors in the Emotional categorisation task, plus an equal number of matched distractor words, are presented, and participants are asked to indicate whether they recognise it from the Emotional categorisation task. Accuracy and reaction times on positive vs negative stimuli are compared between those receiving drug and placebo.
Measured: Assessed during the research visit after the seventh day of atorvastatin or placebo administration, i.e. on the eight day after the patient started taking atorvastatin or placebo
Secondary outcomes (2)
Accuracy and reaction times during reward processing
During a computer-based task, participants are instructed to learn and select which images are associated with wins rather than losses. Accuracy and reaction times are assessed and compared between those receiving drug and placebo.
Measured: Assessed during the research visit after the seventh day of atorvastatin or placebo administration, i.e. on the eight day after the patient started taking atorvastatin or placebo
Changes in C-Reactive Protein levels
Changes in high sensitivity-C Reactive Protein (hs-CRP) from baseline to seven-day, comparing those receiving drug and placebo
Measured: A blood sample will be drawn on the day of randomisation and on the day of the research visit (i.e. after the seventh day on atorvastatin or placebo)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2019
- Study start19 Jun 2019
- Primary completion1 Feb 2020
- Study completion1 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomised, in a double-blind fashion, to either placebo or atorvastatin. The randomisation code will be drawn up by a researcher not involved in the study using an online randomisation tool (https://www.sealedenvelope.com/simple-randomiser/v1/lists).
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Wellcome Trust
- Responsible party
- Sponsor
- Investigators
- Philip J Cowen, MBBS, MD, FRPsych, Principal investigator, University of Oxford, Medical Sciences Division, Department of Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03966859
- Sponsor's protocol ID
- R61966/RE001
- Status last verified
- Nov 2020
- First submitted
- 20 May 2019
- Last updated
- 1 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: To comply with the General Data Protection Regulation (GDPR) and the new Data Protection Act, personal data will be deleted as soon as possible after it is no longer needed for the study. Screening information: For volunteers who do not wish to be contacted for future studies, screening information (including contact details) will be stored for up to one year of completing study analyses, and then destroyed by shredding. Contact details may be retained after the end of the study for participants who have agreed to be contacted for future studies. Consent forms: Consent forms will be kept for 10 years after the end of the study, and then destroyed by shredding.
Publications
Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, Blumenthal R, Danesh J, Smith GD, DeMets D, Evans S, Law M, MacMahon S, Martin S, Neal B, Poulter N, Preiss D, Ridker P, Roberts I, Rodgers A, Sandercock P, Schulz K, Sever P, Simes J, Smeeth L, Wald N, Yusuf S, Peto R. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016 Nov 19;388(10059):2532-2561. doi: 10.1016/S0140-6736(16)31357-5. Epub 2016 Sep 8.
PubMed 27616593Cooper CM, et al. Psychological Medicine 2017; Page 1 of 10. doi:10.1017/S00332917170023792017
Cowen PJ, Browning M. What has serotonin to do with depression? World Psychiatry. 2015 Jun;14(2):158-60. doi: 10.1002/wps.20229. No abstract available.
PubMed 26043325Felger JC, Treadway MT. Inflammation Effects on Motivation and Motor Activity: Role of Dopamine. Neuropsychopharmacology. 2017 Jan;42(1):216-241. doi: 10.1038/npp.2016.143. Epub 2016 Aug 2.
PubMed 27480574Harmer CJ, Shelley NC, Cowen PJ, Goodwin GM. Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. Am J Psychiatry. 2004 Jul;161(7):1256-63. doi: 10.1176/appi.ajp.161.7.1256.
PubMed 15229059Harmer CJ, Duman RS, Cowen PJ. How do antidepressants work? New perspectives for refining future treatment approaches. Lancet Psychiatry. 2017 May;4(5):409-418. doi: 10.1016/S2215-0366(17)30015-9. Epub 2017 Jan 31.
PubMed 28153641Jain MK, Ridker PM. Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov. 2005 Dec;4(12):977-87. doi: 10.1038/nrd1901.
PubMed 16341063Jha MK, Trivedi MH. Personalized Antidepressant Selection and Pathway to Novel Treatments: Clinical Utility of Targeting Inflammation. Int J Mol Sci. 2018 Jan 12;19(1):233. doi: 10.3390/ijms19010233.
PubMed 29329256GBD 2015 DALYs and HALE Collaborators. Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016 Oct 8;388(10053):1603-1658. doi: 10.1016/S0140-6736(16)31460-X.
PubMed 27733283Kilic FS, Ozatik Y, Kaygisiz B, Baydemir C, Erol K. Acute antidepressant and anxiolytic effects of simvastatin and its mechanisms in rats. Neurosciences (Riyadh). 2012 Jan;17(1):39-43.
PubMed 22246008Kohler-Forsberg O, Gasse C, Berk M, Ostergaard SD. Do Statins Have Antidepressant Effects? CNS Drugs. 2017 May;31(5):335-343. doi: 10.1007/s40263-017-0422-3.
PubMed 28303466Li H, Wang C, Zhang S, Sun S, Li R, Zou M, Cheng G. Safety Profile of Atorvastatin 80 mg: A Meta-Analysis of 17 Randomized Controlled Trials in 21,910 Participants. Drug Saf. 2016 May;39(5):409-19. doi: 10.1007/s40264-016-0394-0.
PubMed 26860922Macin SM, Perna ER, Farias EF, Franciosi V, Cialzeta JR, Brizuela M, Medina F, Tajer C, Doval H, Badaracco R. Atorvastatin has an important acute anti-inflammatory effect in patients with acute coronary syndrome: results of a randomized, double-blind, placebo-controlled study. Am Heart J. 2005 Mar;149(3):451-7. doi: 10.1016/j.ahj.2004.07.041.
PubMed 15864233McCabe C, Mishor Z, Cowen PJ, Harmer CJ. Diminished neural processing of aversive and rewarding stimuli during selective serotonin reuptake inhibitor treatment. Biol Psychiatry. 2010 Mar 1;67(5):439-45. doi: 10.1016/j.biopsych.2009.11.001. Epub 2009 Dec 24.
PubMed 20034615Miller AH, Haroon E, Felger JC. Therapeutic Implications of Brain-Immune Interactions: Treatment in Translation. Neuropsychopharmacology. 2017 Jan;42(1):334-359. doi: 10.1038/npp.2016.167. Epub 2016 Aug 24.
PubMed 27555382
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Seven-Day Atorvastatin Administration on Emotional Processing, Reward Processing, and Inflammation in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03966859
- Acronym / sponsor ID
- R61966/RE001
- Conditions
- Healthy
- Keywords
- Atorvastatin, Emotional processing, Reward processing, Inflammation (C-Reactive Protein)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Wellcome Trust
- Study start
- 19 Jun 2019 (actual)
- Primary completion
- 1 Feb 2020 (actual)
- Study completion
- 1 Feb 2020 (actual)
- First posted
- 29 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Work in our group has revealed that short-term (7-day) administration of antidepressants produces positive biases in the processing of emotional information in healthy volunteers. Such effect might be an important neuropsychological mechanism of antidepressant action.
The current study will investigate the effect of seven-day administration of atorvastatin 20mg on emotional and reward processing tasks in healthy volunteers. There is evidence that statins may exert antidepressant effects via anti-inflammatory and anti-oxidant pathways, and it is therefore predicted that atorvastatin will have positive effects on emotional and reward processing.
Detailed description
Depression is common and associated with considerable health disability. Traditional antidepressants mainly work by modulating monoamine levels in the synaptic cleft; however, the evidence that depression is caused by impaired serotonin or noradrenaline activity is weak and inconsistent, and indeed current antidepressant strategies remain burdened by partial efficacy, poor side-effects profile, and a slow onset of therapeutic action. Therefore, there is a pressing need to develop antidepressant medications with novel non-monoaminergic mechanisms of action - or, conversely, to identify alternative pathophysiological pathways leading to depression that can be targeted with new drugs. Intriguingly, there is growing evidence that both peripheral and central inflammation play a role in the pathophysiology of depression.
Patients with depression consistently show negative biases in emotional processing, which are believed to play a key role in the aetiology and maintenance of their clinical symptoms. Overall, robust evidence suggests that early changes in emotional processing can serve as valid surrogate markers of antidepressant efficacy; for example, seven days' treatment with selective serotonin and noradrenaline reuptake inhibitors (citalopram and reboxetine respectively) compared to placebo decreases the recognition of negative facial expressions and recall of negative versus positive stimuli in healthy volunteers. Conversely, another study using the pro-inflammatory cytokine interferon-α showed that inflammatory-mediated depression can be associated with an increased recognition of negative facial expressions. Furthermore, depression associated with inflammation is characterised by significant symptoms of anhedonia, which has been linked to diminished neural responses to reward anticipation. Such reward-deficit is particularly refractory to conventional serotoninergic and noradrenergic antidepressants, and even the antidepressant bupropion (a noradrenaline and dopamine reuptake inhibitor), whilst inducing positive changes in emotional processing, appears to worsen reward processing. However, the reversal of this deficit in reward processing is still considered as a valuable marker of target engagement for anti-inflammatory drugs in depression, as a more sensitive outcome measure than traditional rating scales designed to capture the global clinical symptomatology.
The 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors or statins are recommended and have been widely used since the '80s for the primary and secondary prevention of cardiovascular diseases. It is now established that these medications have significant anti-inflammatory effects that are independent from their lipid-lowering properties, as well as appearing early in treatment only after seven day of administration. Statins are considered extremely safe drugs: their more common side-effect are muscle pain or weakness (usually mild and quickly responding to stopping or switching medication) and elevation of liver transaminases (significant only in case of pre-existing hepatic disease), whereas more serious adverse events include rhabdomyolysis (very rare but severe myopathy associated with elevated creatine kinase and myoglobinuria), new-onset diabetes mellitus (in predisposed individual with pre-existing hyperglycaemia), and haemorrhagic stroke (in patients with prior haemorrhagic stroke or lacunar infarct); however, clinical trials have ultimately concluded that such adverse events attributed to statin therapy in routine practice are not actually caused by it, especially at doses lower than 80mg/day and when used for less than 52 weeks. Other common (≥ 1/100, < 1/10) but usually mild side-effects include: nasopharyngitis, pharyngo-laryngeal pain, epistaxis, headache, and gastrointestinal disturbances (constipation, diarrhoea, flatulence, dyspepsia, nausea). Importantly, a potential antidepressant effect for statins has been confirmed in animals, as well as clinically in observational and interventional studies. Although their anti-inflammatory and anti-oxidant properties have been involved, the mechanisms underlying the antidepressant effects of statins remain unclear, therefore further translational studies have been advocated in order to elucidate this aspect.
In this exploratory study, we will investigate the effect of seven-day administration of atorvastatin 20mg once daily compared to placebo on emotional and reward processing tasks in 50 healthy volunteers. In view of the previous evidence that statins may exert antidepressant effects via anti-inflammatory and anti-oxidant pathways, we predict that atorvastatin will have positive effect on emotional and reward processing.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Participants will be randomised, in a double-blind fashion, to either placebo or atorvastatin. The randomisation code will be drawn up by a researcher not involved in the study using an online randomisation tool (https://www.sealedenvelope.com/simple-randomiser/v1/lists).
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: Lactose placeboParticipants will receive lactose placebo tablets, encapsulated in opaque capsules, and will be asked to take one capsule daily for seven days at night-time, by mouth |
| Atorvastatin | Experimental | Drug: Atorvastatin 20mgParticipants will receive 20mg atorvastatin tablets, encapsulated in opaque capsules, and will be asked to take one capsule daily for seven days at night-time, by mouth |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Male or female
- Aged 18-50 years
- Sufficiently fluent English to understand and complete the tasks
- Body Mass Index in the range of 18-30
- Participant is willing and able to give informed consent for participation in the study
Key exclusion criteria (9 listed)
- Currently any regular medications (except the contraceptive pill)
- History or current significant psychiatric illness
- Current alcohol or substance misuse disorder
- History or current significant hepatic disease
- History or current significant neurological condition (e.g. epilepsy)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atorvastatin 20mgAlso: Lipitor, Atorvaoral dose, once daily for 7 days | Drug | Atorvastatin |
| Lactose placeboAlso: placebooral dose, once daily for 7 days | Other | Placebo |
Primary outcome
Accuracy and reaction times during facial expression recognition task
Time frame: Assessed during the research visit after the seventh day of atorvastatin or placebo administration, i.e. on the eight day after the patient started taking atorvastatin or placebo
Faces representing varying degrees [from "neutral" (0%) to "full prototypical emotion" (100%) of basic emotions (happiness, fear, anger, disgust, sadness, surprise)] are displayed on the screen and participants are asked to quickly and correctly classify them. Accuracy and reaction times on positive vs negative stimuli are compared between those receiving drug and placebo.
Accuracy and reaction times during faces dot-probe task
Time frame: Assessed during the research visit after the seventh day of atorvastatin or placebo administration, i.e. on the eight day after the patient started taking atorvastatin or placebo
Faces acting as positive or negative emotional stimuli (happy or fearful facial expressions) are presented together with a matched neutral face. One is presented above and one below a central fixation point. Subsequently, a probe appears behind one of the two faces and participants are asked to quickly indicate the position of the probe. Accuracy and reaction times on positive vs negative stimuli are compared between those receiving drug and placebo.
Accuracy and reaction times during emotional categorisation task
Time frame: Assessed during the research visit after the seventh day of atorvastatin or placebo administration, i.e. on the eight day after the patient started taking atorvastatin or placebo
Words describing positive and negative personality characteristics are presented, and participants are asked to quickly indicate whether they would like or dislike being described with the presented word. Accuracy and reaction times on positive vs negative stimuli are compared between those receiving drug and placebo.
Accuracy during emotional recall task
Time frame: Assessed during the research visit after the seventh day of atorvastatin or placebo administration, i.e. on the eight day after the patient started taking atorvastatin or placebo
After a delay from the Emotional categorisation task, participants are asked to recall and write down as many words as possible from it. Accuracy in recall of positive vs negative stimuli are compared between those receiving drug and placebo.
Accuracy and reaction times during emotional recognition memory task
Time frame: Assessed during the research visit after the seventh day of atorvastatin or placebo administration, i.e. on the eight day after the patient started taking atorvastatin or placebo
The original personality descriptors in the Emotional categorisation task, plus an equal number of matched distractor words, are presented, and participants are asked to indicate whether they recognise it from the Emotional categorisation task. Accuracy and reaction times on positive vs negative stimuli are compared between those receiving drug and placebo.
2 secondary outcomes
Accuracy and reaction times during reward processing
Time frame: Assessed during the research visit after the seventh day of atorvastatin or placebo administration, i.e. on the eight day after the patient started taking atorvastatin or placebo
Changes in C-Reactive Protein levels
Time frame: A blood sample will be drawn on the day of randomisation and on the day of the research visit (i.e. after the seventh day on atorvastatin or placebo)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2020.
- Background: PubMed 27616593Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, Blumenthal R, Danesh J, Smith GD, DeMets D, Evans S, Law M, MacMahon S, Martin S, Neal B, Poulter N, Preiss D, Ridker P, Roberts I, Rodgers A, Sandercock P, Schulz K, Sever P, Simes J, Smeeth L, Wald N, Yusuf S, Peto R. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016 Nov 19;388(10059):2532-2561. doi: 10.1016/S0140-6736(16)31357-5. Epub 2016 Sep 8.
- BackgroundCooper CM, et al. Psychological Medicine 2017; Page 1 of 10. doi:10.1017/S00332917170023792017
- Background: PubMed 26043325Cowen PJ, Browning M. What has serotonin to do with depression? World Psychiatry. 2015 Jun;14(2):158-60. doi: 10.1002/wps.20229. No abstract available.
- Background: PubMed 27480574Felger JC, Treadway MT. Inflammation Effects on Motivation and Motor Activity: Role of Dopamine. Neuropsychopharmacology. 2017 Jan;42(1):216-241. doi: 10.1038/npp.2016.143. Epub 2016 Aug 2.
- Background: PubMed 15229059Harmer CJ, Shelley NC, Cowen PJ, Goodwin GM. Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. Am J Psychiatry. 2004 Jul;161(7):1256-63. doi: 10.1176/appi.ajp.161.7.1256.
- Background: PubMed 28153641Harmer CJ, Duman RS, Cowen PJ. How do antidepressants work? New perspectives for refining future treatment approaches. Lancet Psychiatry. 2017 May;4(5):409-418. doi: 10.1016/S2215-0366(17)30015-9. Epub 2017 Jan 31.
- Background: PubMed 16341063Jain MK, Ridker PM. Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov. 2005 Dec;4(12):977-87. doi: 10.1038/nrd1901.
- Background: PubMed 29329256Jha MK, Trivedi MH. Personalized Antidepressant Selection and Pathway to Novel Treatments: Clinical Utility of Targeting Inflammation. Int J Mol Sci. 2018 Jan 12;19(1):233. doi: 10.3390/ijms19010233.
- Background: PubMed 27733283GBD 2015 DALYs and HALE Collaborators. Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016 Oct 8;388(10053):1603-1658. doi: 10.1016/S0140-6736(16)31460-X.
- Background: PubMed 22246008Kilic FS, Ozatik Y, Kaygisiz B, Baydemir C, Erol K. Acute antidepressant and anxiolytic effects of simvastatin and its mechanisms in rats. Neurosciences (Riyadh). 2012 Jan;17(1):39-43.
- Background: PubMed 28303466Kohler-Forsberg O, Gasse C, Berk M, Ostergaard SD. Do Statins Have Antidepressant Effects? CNS Drugs. 2017 May;31(5):335-343. doi: 10.1007/s40263-017-0422-3.
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- Individual participant dataSharing planned: No. To comply with the General Data Protection Regulation (GDPR) and the new Data Protection Act, personal data will be deleted as soon as possible after it is no longer needed for the study. Screening information: For volunteers who do not wish to be contacted for future studies, screening information (including contact details) will be stored for up to one year of completing study analyses, and then destroyed by shredding. Contact details may be retained after the end of the study for participants who have agreed to be contacted for future studies. Consent forms: Consent forms will be kept for 10 years after the end of the study, and then destroyed by shredding.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philip J Cowen, MBBS, MD, FRPsych principal investigator
University of Oxford, Medical Sciences Division, Department of Psychiatry
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Atorvastatin 20mg in people with Healthy, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Accuracy and reaction times during facial expression recognition task (time frame: Assessed during the research visit after the seventh day of atorvastatin or placebo administration, i.e. on the eight day after the patient started taking atorvastatin or placebo). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03966859, which also lists 21 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2020.