Preventing adverse events of chemotherapy by educating patients about the nocebo effect (RENNO study) - study protocol of a randomized controlled trial with gastrointestinal cancer patients.

BACKGROUND: Patients undergoing chemotherapy are highly burdened by side effects. These may be caused by the pharmacodynamics of the drug or be driven by psychological factors such as negative expectations or pre-conditioning, which reflect nocebo effects. As such, negative pre-treatment expectations or prior experiences might exacerbate the burden of chemotherapy side effects. Educating patients about this nocebo effect has been put forward as a potential strategy to optimize patients' pre-treatment expectations. In this study, we evaluate whether a briefing about the nocebo effect is efficacious in reducing side effects.

METHODS: In this exploratory study, a total number of n = 100 outpatients with newly diagnosed gastrointestinal cancers are randomized 1:1 to an information session about the nocebo effect (nocebo-education) or an attention control group (ACG) with matching interaction time. Assessments take place before the intervention (T1 pre), post-intervention (T1 post), and 10 days (T2) and 12 weeks (T3) after the initial chemotherapy. The primary outcomes are the patient-rated number and intensity of side effects at 10-days and at 12-weeks follow-up. Secondary outcomes include coping with side effects, tendency to misattribute symptoms, compliance intention, attitude towards the chemotherapy, co-medication to treat side effects and the clinician-rated severity of toxicity. Further analyses are conducted to investigate whether a potential beneficial effect is mediated by a change of expectations before and after the intervention.

DISCUSSION: Informing patients about the nocebo effect might be an innovative and feasible intervention to reduce the burden of side effects and strengthen patients' perceived control over adverse symptoms.

TRIAL REGISTRATION: The trial is registered at the German Clinical Trials Register (ID: DRKS00009501 ; retrospectively registered on March 27, 2018). The first patient was enrolled on September 29, 2015.