Investigating the Effects of Typhoid Vaccine on Sleep in Healthy Volunteers
NCT ID: NCT02628054
Last Updated: 2018-05-14
Study Results
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Basic Information
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COMPLETED
NA
16 participants
INTERVENTIONAL
2015-02-28
2015-07-31
Brief Summary
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Detailed Description
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Raised circulating pro-inflammatory cytokines exhibited during chronic medical illness, such as rheumatoid arthritis, are frequently associated with higher rates of co-morbid depression compared to the general population. Medically healthy individuals with major depression have also been shown to have raised pro-inflammatory cytokine levels. Moreover, administration of interferon-α (IFN-α), a recombinant form of inflammatory cytokine that is commonly used as a therapy for hepatitis C virus (HCV) and certain cancers, is well documented to precipitate depression and cognitive impairment in 30-50% of patients. In a previous study in this Department the investigators showed, using magnetic resonance spectroscopy (MRS), that IFN- α increased markers of glutamate activity. This is of particular interest because of the postulated role of glutamate in mood regulation and cognition.
Converging evidence of the link between inflammation and depression has therefore led to the hypothesis that chronic low-grade inflammation could lead to more persistent alterations in neuropsychological function that might be instrumental in the pathogenesis of major depression. However, the mechanisms for this potential modulation of mood and cognitive function remain unclear.
In order to examine the relationship between inflammation and depression, experimental models of inflammation have been developed that involve exogenous administration of cytokines or cytokine-inducers, for example salmonella typhi (typhoid) vaccination. This study will utilise typhoid vaccination as a model of acute inflammatory challenge in healthy volunteers, which has previously been shown to stimulate a mild, non-sickness inducing inflammatory response that significantly increases levels of the pro-inflammatory cytokine, interleukin (IL)-6, in a safe manner without increasing symptoms of illness, body temperature and blood pressure. This model has been shown to elicit a transient depression-like syndrome in healthy volunteers, including a range of behavioural changes such as cognitive dysfunction, fatigue and modulation of subjective ratings of mood. The investigators believe this will serve as a good model to investigate effects of immune activation on sleep.
Sleep electroencephalogram (EEG) recordings will explore the effects of immune activation on sleep, as sleep changes are observed in clinical depression. Healthy volunteers will be recruited for this study, so that the investigators can investigate the effects of inflammatory challenge in participants that do not currently have an inflammatory condition.
The present exploratory study therefore aims to enhance the investigators understanding of the intriguing link between inflammation and emotional dysfunction by examining the effects of inflammatory challenge using typhoid vaccine on sleep using a detailed psychiatric assessment and sleep EEG recordings.
Conditions
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Study Design
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RANDOMIZED
CROSSOVER
BASIC_SCIENCE
TRIPLE
Study Groups
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Typhoid Vaccine
Typhoid vaccination in single 0.5mL injections into the non-dominant deltoid muscle in the arm
Typhoid Vaccine
Typhoid Vaccine injection given 7 days apart
Placebo
A single 0.5mL injection of 0.9% sodium chloride saline solution into the non-dominant deltoid muscle in the arm
Placebo
Saline injection given 7 days apart
Interventions
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Typhoid Vaccine
Typhoid Vaccine injection given 7 days apart
Placebo
Saline injection given 7 days apart
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Healthy adults, Male or Female, aged 18 to 40 years.
* Not currently taking any medications (except the contraceptive pill).
* Good sleeper determined by self-report and sleep screening interview
Exclusion Criteria
* Any current or previous Axis 1 psychiatric disorder on DSM-5
* Diagnosis of current sleep disorder
* Any significant current medical condition likely to interfere with the conduct of the study or analysis of data
* Typhoid vaccination within the last 3 years
* Any vaccination within the last 6 months
* History of allergies to drugs or vaccines or any component of the typhoid vaccine
* Congenital or acquired immune deficiency (including participants receiving immunosuppressive or antimitotic drugs)
* Bleeding disorder, e.g. haemophilia or thrombocytopenia
* Current or recent physical illness or infection within previous 2 weeks
* Steroidal or non-steroidal anti-inflammatory medication within preceding 2 weeks, including aspirin and ibuprofen
* Current substance misuse
* Child bearing age and not using reliable form of contraception
* Has taken part in a psychological or medical experiment involving taking any kinds of drugs within the last 6 weeks
* Pregnant or breast feeding
18 Years
40 Years
ALL
Yes
Sponsors
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University of Oxford
OTHER
Responsible Party
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Principal Investigators
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Ann L Sharpley, BSc, PhD
Role: PRINCIPAL_INVESTIGATOR
Psychopharmacology Research Unit
References
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Anisman H. Cascading effects of stressors and inflammatory immune system activation: implications for major depressive disorder. J Psychiatry Neurosci. 2009 Jan;34(1):4-20.
Brydon L, Harrison NA, Walker C, Steptoe A, Critchley HD. Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans. Biol Psychiatry. 2008 Jun 1;63(11):1022-9. doi: 10.1016/j.biopsych.2007.12.007. Epub 2008 Feb 1.
Brydon L, Walker C, Wawrzyniak A, Whitehead D, Okamura H, Yajima J, Tsuda A, Steptoe A. Synergistic effects of psychological and immune stressors on inflammatory cytokine and sickness responses in humans. Brain Behav Immun. 2009 Feb;23(2):217-24. doi: 10.1016/j.bbi.2008.09.007. Epub 2008 Sep 20.
Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008 Jan;9(1):46-56. doi: 10.1038/nrn2297.
Felger JC, Lotrich FE. Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience. 2013 Aug 29;246:199-229. doi: 10.1016/j.neuroscience.2013.04.060. Epub 2013 May 3.
Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD. Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol Psychiatry. 2009 Sep 1;66(5):407-14. doi: 10.1016/j.biopsych.2009.03.015. Epub 2009 May 7.
Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Dolan RJ, Critchley HD. Neural origins of human sickness in interoceptive responses to inflammation. Biol Psychiatry. 2009 Sep 1;66(5):415-22. doi: 10.1016/j.biopsych.2009.03.007. Epub 2009 May 1.
Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009 May 1;65(9):732-41. doi: 10.1016/j.biopsych.2008.11.029. Epub 2009 Jan 15.
Motivala SJ, Sarfatti A, Olmos L, Irwin MR. Inflammatory markers and sleep disturbance in major depression. Psychosom Med. 2005 Mar-Apr;67(2):187-94. doi: 10.1097/01.psy.0000149259.72488.09.
Raison CL, Borisov AS, Broadwell SD, Capuron L, Woolwine BJ, Jacobson IM, Nemeroff CB, Miller AH. Depression during pegylated interferon-alpha plus ribavirin therapy: prevalence and prediction. J Clin Psychiatry. 2005 Jan;66(1):41-8. doi: 10.4088/jcp.v66n0106.
Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006 Jan;27(1):24-31. doi: 10.1016/j.it.2005.11.006. Epub 2005 Nov 28.
Wright CE, Strike PC, Brydon L, Steptoe A. Acute inflammation and negative mood: mediation by cytokine activation. Brain Behav Immun. 2005 Jul;19(4):345-50. doi: 10.1016/j.bbi.2004.10.003. Epub 2004 Dec 8.
Sharpley AL, Cooper CM, Williams C, Godlewska BR, Cowen PJ. Effects of typhoid vaccine on inflammation and sleep in healthy participants: a double-blind, placebo-controlled, crossover study. Psychopharmacology (Berl). 2016 Sep;233(18):3429-35. doi: 10.1007/s00213-016-4381-z. Epub 2016 Aug 9.
Other Identifiers
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MSD-IDREC-C3-2014-011
Identifier Type: -
Identifier Source: org_study_id
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