Effects of a Multidisciplinary Intervention on Fatigue in Lymphoma Survivors With Chronic Fatigue: Protocol for a Randomized Controlled Trial (REFUEL).

BACKGROUND

Chronic fatigue (CF) is a highly disabling late effect after cancer, affecting 25% to 40% of lymphoma survivors years after cancer treatment. There is a lack of randomized controlled trials testing interventions to reduce fatigue levels among survivors with CF.

OBJECTIVE

The primary aim of the Randomized Controlled Trial in Chronically Fatigued Lymphoma Survivors (REFUEL) is to examine the effects of a multidisciplinary intervention on the level of fatigue among lymphoma survivors with CF before and immediately after the intervention (3 months after randomization). Secondary aims are to (1) investigate the effects of the intervention on the level of fatigue 6 and 9 months after randomization and the effects on health-related quality of life (HRQoL); other patient-reported outcome measures; and physical fitness 3, 6, and 9 months after randomization; (2) evaluate the cost-utility of the intervention; (3) examine the effect of the intervention on HRQoL among the survivors' partners; and (4) investigate the long-term perceived benefits and daily use of acquired self-management strategies, as well as measure changes in fatigue, daily functioning, HRQoL, mental health, and work-life balance management within each group at 1- and 2-year follow-ups.

METHODS

The REFUEL trial is a 2-armed randomized controlled trial. Lymphoma survivors (2-12 years after diagnosis) with CF are randomly allocated to a 12-week multidisciplinary intervention including patient education, physical exercise, a cognitive behavioral therapy-based group program, and individual nutrition counseling or to usual care. Fatigue is measured by the Chalder Fatigue Questionnaire. Other patient-reported outcome measures are measured by validated questionnaires (eg, the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire, the Patient Health Questionnaire-9, and the Generalized Anxiety Disorder-7). Cardiorespiratory fitness is measured as peak oxygen consumption during a cardiopulmonary exercise test or indirectly using a modified Balke treadmill protocol. Muscle strength is assessed by push-ups and leg press. The primary analyses will be performed using a generalized linear mixed model for repeated measures, with an intention-to-treat approach.

RESULTS

A total of 150 survivors were included from December 2021 to March 2023. Three-month postrandomization assessments were completed in June 2023 and 2-year follow-up assessments were completed in June 2025.

CONCLUSIONS

The REFUEL trial will provide new and highly needed scientific evidence about the effects of a multidisciplinary intervention on the level of fatigue and secondary outcomes regarding HRQoL aspects among lymphoma survivors with CF.

TRIAL REGISTRATION

ClinicalTrials.gov NCT05130099; https://www.clinicaltrials.gov/study/NCT05130099.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/69336.