A double-blind, placebo-controlled randomized trial of creatine for the cancer anorexia/weight loss syndrome (N02C4): An Alliance trial

Background: Multiple pilot studies, including one in colorectal cancer patients, suggest that creatine, an amino acid derivative, augments muscle, improves strength, and thereby could palliate the cancer anorexia/weight loss syndrome. Patients and methods: In this randomized, double-blind, placebo-controlled trial, incurable patients with this syndrome were assigned creatine (20 g/day load×5 days followed by 2 g/day orally) versus identical placebo. Patients were weighed once a week for 1 month and then monthly. Patients were also assessed over 1 month for appetite and quality of life (validated questionnaires), fist grip strength, body composition (bioelectrical impedance), and adverse events. The primary endpoint was 10% or greater weight gain from baseline during the first month. Results: Within this combined cohort of 263 evaluable patients (134 received creatine and 129 placebo), only 3 gained ≥ 10% of their baseline weight by 1 month: two creatine-treated and the other placebo-exposed (P = 1.00). Questionnaire data on appetite, quality of life, and activities of daily living showed no statistically significant differences between groups. Similarly, no statistically significant differences between groups were observed for fist-grip strength or body composition. Rates and severity of adverse events were comparable between groups. Finally, a median survival of 230 and 239 days were observed in the creatine and placebo groups, respectively (P = 0.70). Conclusion: Creatine, as prescribed in this trial, had no effect on the cancer anorexia/weight loss syndrome.