Humoral and Cellular Immune Responses After Influenza Vaccination in Patients With Postcancer Fatigue and in Patients With Chronic Fatigue Syndrome
Condition: Postcancer Fatigue; Chronic Fatigue Syndrome
MeSH terms: Fatigue Syndrome, Chronic; Syndrome; Fatigue
Study type: Interventional

Summary: 
      Postcancer fatigue (PCF) is a frequently occurring, severe and invalidating problem,
      impairing quality of life. Patients with chronic fatigue syndrome (CFS) also suffer from
      severe fatigue symptoms. Although it is possible to effectively treat CFS, the nature of the
      underlying physiology remains unclear. The presence of an underlying immunological problem
      has been suggested as an explanation for PCF and CFS. The aim of this study is to compare the
      humoral and cellular immune responses upon influenza vaccination in PCF patients, CFS
      patients, non-fatigued cancer survivors, and healthy controls.

      PCF (n=20) and CFS patients (n=20) will be vaccinated against influenza. Age and gender
      matched non-fatigued cancer survivors (n=20) and healthy controls (n=20) will be included for
      comparison. Antibody responses will be measured at baseline and at day 21 by a
      hemagglutination inhibition test. T cell responses will be measured at baseline and at day 7
      by lymphocyte proliferation, activation, and cytokine secretion.
    

Detailed description: 
      Background PCF is a frequently occurring, severe, and invalidating problem in cancer
      survivors, impairing quality of life. The prevalence of PCF observed in longitudinal
      follow-up studies ranged from 19-39%. Cognitive behavior therapy, especially designed for
      PCF, seemed to be an effective treatment option for PCF. However, although it is now possible
      to effectively treat PCF, the nature of the underlying physiology of PCF remains unclear.

      Hypotheses about mechanisms explaining cancer-related fatigue have already been described,
      including dysregulation of brain serotonin, dysregulation of the
      hypothalamic-pituitary-adrenal axis responsiveness, disruption of the circadian rhythm,
      alterations in muscle and ATP metabolism, and activation of the vagal afferent nerve.
      Furthermore, the presence of an underlying immunological problem has been suggested as an
      explanation for PCF.

      Another group of patients suffering from severe fatigue symptoms are patients with CFS. The
      estimated worldwide prevalence of CFS is 0.4-1%. In the Netherlands, about 100.000 patients
      are suffering from chronic fatigue, of which 30.000 to 40.000 suffer from CFS. In contrast to
      fatigue in patients with PCF, in patients with CFS no clear precipitating factor could be
      identified. Also for patients with CFS, a cognitive behavior therapy is designed, which is
      proven to be effective, but the pathophysiological mechanism of CFS remains unclear.

      Hypotheses explaining the pathophysiological mechanism of CFS include morphological and
      metabolic alterations in the brain, diminished central activation of muscles, altered central
      nervous system functioning, a neuroendocrine disturbance, or cognitive impairment.
      Furthermore, the presence of an underlying immunological problem has been suggested as an
      explanation for CFS.

      If an underlying immunological problem is present, PCF and CFS patients might have an altered
      response to vaccination.

      Aim Therefore, the aim of this study is to compare the humoral and cellular immune responses
      upon vaccination, using seasonal influenza vaccination as a model of a vaccination, in PCF
      and CFS patients, non-fatigued cancer survivors, and healthy controls.

      Research questions

        1. Is the humoral and/or cellular immune response after influenza vaccination different
           between fatigued patients (PCF and CFS) and non-fatigued individuals?

        2. Is the humoral and/or cellular immune response after influenza vaccination different
           between PCF and CFS patients? Design The immune responses upon influenza vaccination
           will be assessed in 20 PCF patients and in 20 CFS patients. As a control group for PCF
           patients, 20 non-fatigued cancer survivors will be included. Additionally, 20 healthy
           controls will participate in this study as a control group without a cancer history and
           without fatigue symptoms. These four groups will be age- and sex-matched.

      At baseline, participants will complete the Checklist Individual Strength, a questionnaire
      about the current use of medicines, and a questionnaire about their vaccination history. All
      participants will be intramuscularly vaccinated with a single dose of the seasonal influenza
      vaccine. Peripheral blood mononuclear cells will be collected at baseline (day 1) and 7 days
      after vaccination (day 8), and serum will be collected at baseline and 21 days after
      vaccination (day 22). Half a year after vaccination, all participants will be contacted to
      check whether a possible infection by influenza had taken place in the meantime or not.

      The humoral immune responses on influenza vaccination will measured at day 1 and day 22 in
      serum by the haemagglutination-inhibition antibody test. The cellular immune responses will
      be measured at day 1 and day 8 by T lymphocyte proliferation, activation, and cytokine
      secretion.

      Relevance of this study To the best of our knowledge, we are the first to explore both the
      humoral and cellular immune responses after influenza vaccination in both PCF and CFS
      patients. By means of this study, we would like to improve the understanding of the
      underlying physiology of PCF and CFS.
    

Intervention name(s): Seasonal influenza vaccination
Intervention type(s): Biological
Intervention description(s): single dose of influenza vaccination
Intervention model: Single Group Assignment
Masking: None (Open Label)