Clinical Trial: Investigating the Effects of Typhoid Vaccine on Sleep in Healthy Volunteers

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Investigating the Effects of Typhoid Vaccine on Sleep in Healthy Volunteers

Brief Summary: 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.

Detailed Summary:

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
Sponsor: University of Oxford

Current Primary Outcome: 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 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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
  • 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 ]
  • 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 ]
  • 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 ]
  • Change in LSEQ subjective rating scores, following afternoon administration of the typhoid vaccine compared to placebo (saline) injection [ Time Frame: 19 hours ]
  • Randomisation guess, following afternoon administration of the typhoid vaccine compared to placebo (saline) injection [ Time Frame: 19 hours ]


Original Secondary Outcome: Same as current

Information By: University of Oxford

Dates:
Date Received: November 19, 2015
Date Started: February 2015
Date Completion:
Last Updated: December 8, 2015
Last Verified: December 2015