Can open label placebos improve pain and gluten tolerance via open label placebos in fibromyalgia patients? A study protocol for a randomised clinical trial in an outpatient centre.

introductionFibromyalgia syndrome (FMS) is defined as a medical condition with chronic widespread musculoskeletal pain accompanied by mood disorders, fatigue and sleep disturbances. Treatment of this condition can often be challenging. As nutrition in general and nutritional interventions in the context of illness management become more and more important, current research also focuses on the relevance of diets for FMS, including gluten as field of interest. To date, there is no clear evidence that a gluten-free diet or other nutritional interventions are significantly important for the reduction of pain in the context of FMS. Only a very few studies show that FMS patients respond to a gluten-free diet and that cytokine production (also in FMS) can be reduced through the change. However, these studies have not investigated whether and to what extent cognitive factors, such as the expectation of symptom reduction triggered by diet, play a role. Recent research shows that treatment expectation plays an important role in the course of the disease and in the effectiveness of treatment approaches. For example, there are promising pain treatment options using open-label placebos (OLPs), which show that expectation alone, rather than the pharmacological substance of medication, can reduce pain experience. In our study protocol, we hypothesise that treatment expectation can be positively influenced by the given information regarding the placebos, resulting in improved treatment outcomes for pain and indigestions. METHODS AND ANALYSIS: In this trial, patients with FMS will undergo a food challenge and take an OLP (patients will be informed about the placebo), followed by a 3-week OLP treatment. The subjects will be randomised into four groups: (a) gluten-free porridge+neutral OLP instructions; (b) gluten-free porridge+positive OLP instructions; (c) gluten-containing porridge+neutral OLP instructions and (d) gluten-containing porridge+positive OLP instructions. Patients will be recruited via different institutions and support groups in Hamburg. The inclusion criteria are (a) diagnosed FMS, (b) absence of wheat allergy, coeliac disease or pain-related red flags and (c) being a minimum age of 18 years. The study requires 100 subjects to assess the primary outcomes: pain intensity and occurence of indigestion. Secondary outcomes are functional capacity, treatment expectation, and different pain-related and inflammation-related blood parameters. The measure time points will be before and after the food challenge and before and after the 3-week OLP treatment. ETHICS AND DISSEMINATION: Ethical approval was obtained in October 2021 from the Hamburg Medical Ethics Council. The results of the study will be disseminated through publications, presentations and conference meetings. TRIAL REGISTRATION NUMBER: German Clinical Trials Register (DRKS; DRKS00027130).