The Immune and Endocrine Systems in Chronic Non-cancer Patients Treated With Opioids
Condition: Pain; Opioids; Immune System; Endocrine System; Quality of Life
Study type: Observational

Summary: 
      The primary aim is to investigate the dose and time dependent effects of different opioids on
      the immune and endocrine systems.

      The secondary aim is to investigate whether associations between the function of the immune
      and endocrine systems and opioid use influence cognitive function, pain and quality of life.
    

Detailed description: 
      BACKGROUND

      Epidemiological data from the US and Denmark have shown that 3-5% of the population use
      opioids for treatment of chronic pain conditions.

      Long-term use of opioids may cause "classic" opioid-induced adverse effects, but also serious
      consequences such as hyperalgesia, cognitive disorders, and suppression of the immune and
      endocrine systems.

      Relatively few studies suggest that these substances affect hormone function in humans. The
      best studied is the circumstances regarding sex hormones.

      A single systematic study and several clinical observations suggest that both
      pituitary-adrenal function and formation of growth hormone is also reduced by opioids.

      Other studies have shown that not only are hormones changing during treatment with opioids,
      but the immunological function is also affected. There have been shown a link between the
      immunological and hormonal function so that parts of the immune system also affect the
      pituitary-adrenal function.

      Opioid use and misuse per se has long been suspected to be associated with infections because
      both the innate and the adaptive immune system are getting affected through a number of
      mechanisms.

      This study investigates the possibility of hormonal disorders being contributing factor to
      the development of cognitive impairment in patients who are in opioid treatment. The same
      applies to patients' well-being, mood and pain perception.

      STUDY DESIGN

      A cross-sectional study will be carried out at Multidisciplinary Pain Centre, Rigshospitalet,
      investigating opioid treated chronic non-cancer patients. These patients should have been
      treated only with one opioid for more than one month and will be compared to an age,
      educational and sex matched control group of chronic non-cancer patients not treated with
      analgesics.

      STUDY SAMPLE

      The study is an explorative study of 25 opioid treated patients and 25 controls.

      The patients will be included or excluded for either group on the basis of specific
      criterions.

      If the hypotheses of the study seem to be confirmed more patients will be included in order
      to investigate the effects of different opioid substances.

      METHOD

      Data will be collected by a trained medical student, who will administer the instruments and
      retrieve information from the patients' files.

      Hormone assay

      The adrenocortical function will be tested with the 30 min ACTH test. Leydig-cell function,
      IGF, TSH, thyroxine and prolactine will be measured as well.

      Immunology Fresh whole blood will be used for flow cytometry, where the amount of the
      different cells in the immune system will be measured. Furthermore, plasma samples (snap
      frozen) will be collected (biobank).

      The following cell types will be analyzed by using flow cytometry: NK cells, B cells and T
      cells. To study the immune response fresh whole blood will be stimulated with pathogens.
      Production of cytokines will be examined by analyzes of culture supernatants. Possible
      alteration in inflammation will be determined by analysing the plasma samples.

      Establishment of research biobank

      All material is collected as part of the study. A biobank will be established and blood
      samples will be safely stored at Rigshospitalet as long as the study is going on. The purpose
      of the research biobank is to use the samples in follow-up studies.

      Assessment of cognitive function

      Regarding neuropsychological assessment, two instruments were selected:

        1. CRT measures sustained attention or vigilance. It is a computer test, in which through
           headphones, 100 auditory signals are delivered to the patient at random intervals. The
           patient is instructed to press a button as soon as the sound is heard.

        2. DST assesses attention/concentration, recent and working memory. Patients are asked to
           repeat the series of numbers of increasing lengths, in both forward (direct) and
           backward (reverse) order.

      Pain evaluation

      Patients' pain intensity will be assessed using the Brief Pain Inventory (BPI) measuring pain
      at its worst, least and average during the last 24 hours and the current pain intensity.

      Mood

      Depression and anxiety will be evaluated using the Hospitality Anxiety and Depression Scale
      (HADS). Scores above 8 indicates that a depressive or anxiety disorder is likely to be
      present.

      Health-related quality of life

      The Short Form 36 (SF-36) will also be included in the self-administered questionnaire. The
      SF-36 is a 36-item survey that measures eight dimensions of health. Higher scores on the
      SF-36 (range 0 to 100) indicate better health-related quality of life.

      RESULTS

      The results will be analysed by using specific statistic tools as descriptive variables,
      primary outcome, secondary outcome, significance levels, and clinical significance.
    

Observational model: Other
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Pain patients at Multidisciplinary Pain Centre at Rigshospitalet, Denmark
      
Biospecimen description: 
      whole blood/serum
    
Keywords: Pain, opioids, immune system, endocrine system, quality of life