Dismantling open-label placebos and their rationales: A remote 4-arm randomized controlled trial protocol.

OBJECTIVE

To explore the effect of rationales on placebos described honestly as inactive pills, (open-label placebos; OLPs) on chronic pain.

DESIGN

Dismantling 4-arm randomized controlled trial.

SETTING

Remote study with United-States residents.

SUBJECTS: Chronic pain patients aged 18 to 89.

METHODS

We plan to recruit 340 subjects, randomized before consent (Zelen randomization procedure) into one of 4 groups. Participants in a no-treatment group will not receive any OLPs. Participants in the three OLP groups will be told to take an OLP pill twice daily for 21 days. The information participants are given about placebos will vary. Those in the "Standard-OLP" group will be provided with a rationale similar to those used in prior OLP trials. Those in the "Mindfulness-OLP" group will be provided with a rationale taking a mindfulness approach. Those in the "Control-OLP" group (and no-treatment group) will be provided with length-matched information about pain demographics; no placebo information will be given. This dismantling design will allow us to compare rationales (Standard-OLP vs Mindfulness-OLP), and examine the rationale effect (Standard-OLP or Mindfulness-OLP vs. Control-OLP), the placebo effect (Standard-OLP or Mindfulness-OLP vs. No-treatment), and the pill effect (Control-OLP vs no-treatment). Pain intensity over 42 days is the primary outcome.

CONCLUSIONS

This trial will investigate how different components of OLPs impact pain among a chronic pain population. We also highlight novel ways to address limitations of prior OLP studies; namely, lack of blinding and improper controls.