7-day Atorvastatin and Emotional Processing

NCT03966859 | Completed

• 1 other identifier: R61966/RE001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Healthy

Keywords

Atorvastatin; Emotional processing; Reward processing; Inflammation (C-Reactive Protein)

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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.

  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

  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

  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)

Study Arms (2)

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

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

Drug: Atorvastatin 20mg

Interventions

Atorvastatin 20mg DRUG

oral dose, once daily for 7 days

Also known as: Lipitor, Atorva

Atorvastatin

Lactose placebo OTHER

oral dose, once daily for 7 days

Also known as: placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• University of Oxford: lead
• Wellcome Trust: collaborator

Study Sites (1)

Riccardo De Giorgi

Oxford, OX3 7JX, United Kingdom

Location

Related Publications (21)

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• Harmer 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.

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• Macin 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.

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  BACKGROUND

• Parsaik AK, Singh B, Murad MH, Singh K, Mascarenhas SS, Williams MD, Lapid MI, Richardson JW, West CP, Rummans TA. Statins use and risk of depression: a systematic review and meta-analysis. J Affect Disord. 2014 May;160:62-7. doi: 10.1016/j.jad.2013.11.026. Epub 2013 Dec 17.

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MeSH Terms

Conditions

Inflammation

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Philip J Cowen, MBBS, MD, FRPsych

  University of Oxford, Medical Sciences Division, Department of Psychiatry

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The atorvastatin drug and the placebo will be encapsulated in identical capsules. Participants will not be aware of the treatment that they will be receiving; neither will the researcher. Allocation of treatments will be recorded on a Randomisation List, which will be updated when each new participant enters the randomised phase. The list will be held by a scientist uninvolved in the study.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: May 20, 2019
• First Posted: May 29, 2019
• Study Start: June 19, 2019
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2020
• Last Updated: December 1, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)