Pilot study of a muscadine grape extract supplement to decrease fatigue among older cancer survivors.

Abstract

12057 Background: Fatigue is a prevalent symptom among older cancer survivors and is associated with declines in physical function and quality of life (QOL). A proprietary muscadine grape extract supplement (MGES) may decrease fatigue based on pre-clinical data showing effects on oxidative stress, inflammation, and mitochondrial function and clinical observations from a Phase 1 trial suggesting a relationship between higher dose of MGES and decreased fatigue. The objective of this pilot study was to evaluate whether MGES may decrease fatigue and improve function and QOL among older cancer survivors. Methods: We conducted a randomized placebo-controlled pilot study (NCT04495751) of MGE supplementation (4 tablets twice daily, approximately 1280 mg total phenolics) for 12 weeks (wks) among older adult cancer survivors who reported baseline fatigue. Additional eligibility included age ≥65 years, history of solid tumor or lymphoma with no evidence of disease, at least 1 year post completion of active treatment. Fatigue was assessed with the PROMIS Fatigue 7a at baseline, and 2, 4, 8, 12 (primary outcome) and 16 wks. Physical function [Pepper Assessment Tool for Disability (PAT-D, activities of daily living and self-reported mobility subscales, higher scores indicate more limitations), Short Physical Performance Battery (SPPB, higher scores indicate better performance), 6-minute walk] and QOL (PROMIS Global Health) were measured at baseline and 12 wks. Toxicity was assessed using the CTCAE v5. Intention to treat (IIT) analyses utilized t-tests with a one-sided alpha = 0.10 to compare outcomes at 12 wks. Results: Sixty-four adults (mean age 76 years, 78% female, 91% white, 6% black) were randomized. Most common malignancies were breast (50%), lymphoma (12.5%), and prostate (12.5%). Fifty-one participants (80%) completed 12 wks of MGES or placebo with N = 62 evaluable for IIT analysis. There were no ≥grade 3 toxicities; 26 grade 2 toxicities (gastrointestinal) were attributable to study intervention. In IIT analyses, there was no difference in fatigue by randomization at 12 wks (MGE 50.1 vs placebo 51.4, p = 0.22). However, participants randomized to MGES reported improved physical function (PAT-D total score 1.4 vs 1.6, p = 0.07, ADL score 1.2 vs 1.4 p = 0.08, mobility score 1.7 vs 2.2, p = 0.05) and had improved gait speed scores on the SPPB, 3.7 vs 3.3, p = 0.1).There were no differences in total SPPB score (9.8 vs 9.2, p = 0.37), six-minute walk distance (369 vs 349 feet, p = 0.43) and QOL at 12 wks. Conclusions: In this pilot study, MGE supplementation for 12 wks among older cancer survivors did not improve fatigue or QOL compared to placebo but self-reported physical function and gait speed score were improved, suggesting a potential benefit on physical function. Ancillary studies investigating effects on oxidative stress, inflammation, mitochondrial function, and microbiome are on-going. Clinical trial information: NCT04495751 .