Therapeutic Fasting as a Novel Approach to Mitigate Musculoskeletal Symptoms in Breast Cancer Patients undergoing Aromatase Inhibitor Therapy: A Feasibility Study Protocol.

Abstract

Introduction: Aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) or aromatase inhibitor-induced arthralgia (AIA), common side effects of long-term adjuvant endocrine therapy for breast cancer patients, can significantly affect quality of life. Preliminary clinical evidence suggests that fasting may alleviate these symptoms, as demonstrated in conditions such as rheumatoid arthritis and fibromyalgia. This study aims to evaluate the feasibility and acceptability of prolonged therapeutic fasting program, including structured behavioral and educational support, in patients with AIMSS/AIA and explore the applicability of validated measurement tools for assessing symptom burden in preparation for a confirmatory bicentric trial.

Methods: This is a bicentric, single-arm, prospective pilot study. We will enroll 54 participants undergoing endocrine therapy with aromatase inhibitors who suffer from AIMSS/AIA. All participants will receive a 7-day online- prolonged therapeutic fasting intervention (max. 350 kcal/day), consisting of vegetable juices and broths under medical supervision. The primary outcome is the feasibility of prolonged therapeutic fasting during aromatase inhibitor therapy assessed through participant adherence to the fasting protocol and completion rate. As a secondary endpoint, we will assess the feasibility of using validated measurement instruments to collect data on symptoms, quality of life, mindfulness, stress, and sleep quality in preparation for a confirmatory trial. The following well established tools will be used: Numeric Rating Scale (NRS), Visual Analog Scale (VAS), Brief Pain Inventory (BPI), Fibromyalgia Impact Questionnaire (FIQ), Health Assessment Questionnaire-Disability Index (HAQ-DI), WHO-5 Well-Being Index (WHO-5), Mindful Attention Awareness Scale (MAAS), Brief Fatigue Inventory (BFI) and Pittsburgh Sleep Quality Index (PSQI). Specifically, we aim to explore their applicability by evaluating completion rates, participant acceptability, and data completeness within this patient population. Exploratory parameters, including changes in dietary habits, anthropometric data, and cancer-related fatigue will be tracked to contextualize the feasibility findings and inform outcome selection for a future confirmatory trial. An accompanying N-of-1 trial using a mobile application (StudyU) and qualitative interviews will give more insight into individual and subjective changes.

Conclusion: If the intervention proves feasible and well accepted, these findings will support the development of a confirmatory trial designed to investigate the potential clinical benefits and underlying mechanisms of fasting in AIMSS/AIA. Long-term studies incorporating biomarkers and microbiota analysis could further explore the mechanisms underlying symptom improvement and guide personalized treatment strategies.

Trial registration: ClinicalTrials.gov.NCT06172088. Registered 14 December 2023.URL: https://clinicaltrials.gov/study/NCT06172088.