INTRODUCTION: People with cystic fibrosis (PwCF) are at high risk for developing cystic fibrosis (CF)-related diabetes (CFRD), which worsens morbidity and mortality. Although the pathological events leading to the development of CFRD are complex and not completely understood, dietary factors may play a role. For example, habitual intake of dietary added sugar (i.e., sugar not naturally occurring in foods) has been shown to be increased in PwCF and this excess intake of added sugar could increase the risk of CFRD. METHODS AND ANALYSIS/DESIGN: The goal of this ongoing double-blind, randomised, parallel-group clinical trial is to recruit approximately 60 clinically stable adults with CF to determine if a low-added sugar intervention improves beta-cell responsiveness and insulin sensitivity (Aim 1), reduces visceral adipose tissue (VAT) and other ectopic fat deposition (Aim 2) and improves plasma redox status (Aim 3) over 8 weeks compared with a typical CF diet. All foods will be provided. Participant selection criteria include confirmed CF diagnosis without CFRD, ≥18 years of age, and baseline estimated daily total added sugar intake >16 tsp. Eligible participants will be randomised to one of two arms: a low-added sugar diet (<5% of kcal from added sugars) or a high-added sugar (≥13% kcal from added sugars) diet. The two diets will be isocaloric and provide 35%-40% kcal from fat. Participants will be seen in the research unit for a screening, baseline/randomisation and 4-week and 8-week follow-up visits. Major study endpoints are changes in beta-cell responsiveness determined by a glucose-potentiated arginine stimulation test (primary endpoint), VAT assessed by magnetic resonance imagin (MRI) and fasted plasma cysteine redox potential. Diet tolerance, body weight and compliance are monitored weekly by phone by an unblinded study dietitian. All analyses will be intention-to-treat. Changes in study endpoints will be assessed with repeated-measures analysis. Models will assess the effects by study arm, time on study, and the interaction between arm and time on study. ETHICS AND DISSEMINATION: The National Institutes of Health (NIH) funds this study (R01 DK133523). The study protocol was approved by the Emory Institutional Review Board (IRB approval number: 000004517). Any protocol modifications will be reviewed and approved by the IRB prior to implementation and communicated with the study team and participants, as relevant.We will provide reports of the findings to the NIH and Emory IRB in regular progress reports and post the findings on www. CLINICALTRIALS: gov. We will inform the findings of the study to the scientific community through presentations and peer-reviewed publications. Authorship for any resulting publications will follow the guidelines established by the International Committee of Medical Journal Editors. TRIAL REGISTRATION NUMBER: This research study is registered at www. CLINICALTRIALS: gov (NCT05766774).