An Exploratory Analysis of the Association Between Catechol-O-Methyltransferase and Response to a Randomized Open-Label Placebo Treatment for Cancer-Related Fatigue

Abstract

Previous studies have identified catechol-O-methyltransferase (COMT), as a key enzyme influencing sympathetic function. Although the COMT SNP rs4680 and rs4818, are well-studied, little is known about their influence on cancer-related fatigue (CrF) and placebo response. In this study, we examined whether genetic variation in COMT, at the functional SNP rs4680 and linked rs4818, influenced open-label placebo (OLP) responses found in cancer survivors reporting moderate to severe CrF. We randomized cancer survivors (N = 74) reporting moderate-to-severe CrF to receive OLP or to treatment-as-usual (TAU) and assessed if rs4680 and rs4818 were associated with changes in fatigue severity and fatigue-distressed quality of life. At the end of the initial 21 days, the treatments were crossed over and both groups were re-assessed. Participants with the rs4680 high-activity G-allele (G/G or G/A) or rs4818 C/G genotypes reported significant decreases in fatigue severity and improvements in fatigue-distressed quality of life. The COMT rs4818 findings replicated findings in a similar study of OLP in cancer fatigue. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02522988.

Keywords: COMT (rs 4680); COMT rs4818 polymorphism; cancer related fatigue; non-deceptive placebo; placebo effect.