Investigating the Effects of Typhoid Vaccine on Sleep in Healthy Volunteers

May 8, 2018 updated by: University of Oxford
Research studies have found a relationship between the immune system (how the body reacts to an infection) and the development of depression. As it is still unclear how they might be linked the investigators will use a typhoid vaccination to activate the body's immune system and will measure the response by looking at changes in sleep patterns.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Elevated levels of pro-inflammatory cytokines are implicated in the pathogenesis of major depression. Both clinical and animal studies have shown that pro-inflammatory cytokines can induce a behavioural repertoire of symptoms collectively referred to as 'sickness behaviours,' which include cognitive and mood symptoms, such as depression, anxiety, memory impairment, fatigue, anhedonia and sleep disturbance.

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.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Participant is willing and able to give informed consent for participation in the study.
  • 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:

The participant may not enter the study if ANY of the following apply:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Typhoid Vaccine
Typhoid vaccination in single 0.5mL injections into the non-dominant deltoid muscle in the arm
Biological: Typhoid Vaccine
Typhoid Vaccine injection given 7 days apart
Other Names:
  • Typhim Vi®
Placebo Comparator: Placebo
A single 0.5mL injection of 0.9% sodium chloride saline solution into the non-dominant deltoid muscle in the arm
Biological: Placebo
Saline injection given 7 days apart
Other Names:
  • 0.9% sodium chloride saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Acute (night 1) differences in sleep architecture, measured using polysomnography, following afternoon administration of the typhoid vaccine compared to placebo (saline) injection
Time Frame: 19 hours
19 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Interleukin-6 (IL-6) levels following typhoid vaccine compared to placebo (saline) injection
Time Frame: 2 hours
Blood sample taken 2 hours post injection
2 hours
Change in PANAS subjective mood rating scores, following afternoon administration of the typhoid vaccine compared to placebo (saline) injection
Time Frame: 1 hour, 2 hours, 3 hours, 4 hours
1 hour, 2 hours, 3 hours, 4 hours
Change in VAS Bond and Lader subjective mood rating scores, following afternoon administration of the typhoid vaccine compared to placebo (saline) injection
Time Frame: 1 hour, 2 hours, 3 hours, 4 hours
1 hour, 2 hours, 3 hours, 4 hours
Change in adverse effects scores, following afternoon administration of the typhoid vaccine compared to placebo (saline) injection
Time Frame: 1 hour, 2 hours, 3 hours, 4 hours and 19 hours
1 hour, 2 hours, 3 hours, 4 hours and 19 hours
Change in LSEQ subjective rating scores, following afternoon administration of the typhoid vaccine compared to placebo (saline) injection
Time Frame: 19 hours
19 hours
Randomisation guess, following afternoon administration of the typhoid vaccine compared to placebo (saline) injection
Time Frame: 19 hours
19 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Investigators

  • Principal Investigator: Ann L Sharpley, BSc, PhD, Psychopharmacology Research Unit

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2015

Primary Completion (Actual)

July 1, 2015

Study Completion (Actual)

July 1, 2015

Study Registration Dates

First Submitted

November 19, 2015

First Submitted That Met QC Criteria

December 8, 2015

First Posted (Estimate)

December 11, 2015

Study Record Updates

Last Update Posted (Actual)

May 14, 2018

Last Update Submitted That Met QC Criteria

May 8, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MSD-IDREC-C3-2014-011

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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