Table 4

Brief description of the substudies included in the BEAMS study protocol

Substudy titleParticipantsSubstudy details
Morphine/morphine metabolite sub-study55
  • Aim: to determine the relationship between the steady-state plasma concentrations of M3G and M6G along with the effects of renal function with change in breathlessness intensity

  • Blood samples collected at baseline and steady state at trough levels end of week 1 and week 3

Pharmacogenetic substudyAll consenting
  • Aim: identification and assessment of genetic variations in opioid receptor, neuronal, immune, metabolic or signalling pathways that may influence clinical responsiveness to ER morphine for symptomatic treatment of chronic breathlessness

  • Blood sample collection at baseline

Sleep substudy30
20
  • Aim: to investigate the effect that study interventions have on sleep quality

  • Data obtained from Fitbit Charge HR for all participants

  • Thirty participants recruited to non-invasive, home-based sleep studies at baseline and at the end of stage 3

  • Up to 20 participants from two centres (Sydney and Adelaide) will participate in two formal overnight laboratory sleep studies at baseline and at the end of stage 3.

Driving substudy20
  • Aim: assess effects of introducing and steady-state ER morphine use on driving simulator performance in subgroup of participants

  • Short questionnaire to assess driving history

  • Participants from two centres (Sydney and Adelaide) will complete three 30 min office-based driving simulations. One at baseline, one on day 2 and again on day 7 of stage 1.

Caregiver well-being substudyAll consenting
  • Aim: to compare the impact on caregiver well-being between study interventions when compared with baseline

  • Caregivers asked to provide basic demographic data and complete the Zarit burden interview 12-item short-form questionnaire133

  • Assess level of subjective burden at baseline and the end of stages 1, 2, 3 and 4 (or study withdrawal)

Patient and caregiver qualitative substudyAll consenting
  • Aim: to understand the experience of living with chronic breathlessness and the attitudes towards ER morphine use for its symptomatic treatment

  • Limited to participants from Adelaide

  • Separate patient and caregiver qualitative interviews

  • People who decline to participate in the BEAMS study but who fulfil the inclusion criteria will also be offered participation in this substudy.

Economic analysis substudyAll consenting
  • Aim: to compare within trial incremental costs and cost effectiveness of regular low-dose ER morphine using prospectively collected data

  • Data collected will include hospitalisations, presentations to emergency departments, use of primary care, allied health practitioners and palliative care services throughout the study and for 4 weeks after last study medication is given.

Testosterone level substudyAll consenting from stage 4
  • Aim: to further evaluate changes in total testosterone levels given concerns in previous studies that suggest morphine may reduce testosterone levels134 135

  • Prospectively obtained blood samples at baseline and on completion of stage 4

Cortisol substudyAll consenting (who have not been on glucocorticoids in the preceding 4 weeks)
  • Aim: to understand if hypothalamic–pituitary–adrenal axis dysregulation of chronic disease is influenced by reduction in chronic breathlessness as a stressor, with some return of normal diurnal variation.

  • Saliva tests three times each of 8 days across the study.

  • BEAMS, Breathlessness, Exertion And Morphine Sulfate; ER, extended release; M3G, morphine, morphine-3-glucuronid; M6G, morphine-6-glucuronide.