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

Teri W Hoenemeyer, Navneet Kaur Baidwan, Kathryn Hall, Ted J Kaptchuk, Kevin R Fontaine, Tapan S Mehta, Teri W Hoenemeyer, Navneet Kaur Baidwan, Kathryn Hall, Ted J Kaptchuk, Kevin R Fontaine, Tapan S Mehta

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.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Hoenemeyer, Baidwan, Hall, Kaptchuk, Fontaine and Mehta.

Figures

Figure 1
Figure 1
Consort diagram.
Figure 2
Figure 2
Forest plot showing the mean difference in the FSS scores among the genotype categories within SNPs rs4680 and rs4818 when those randomized to OLP were compared to TAU.
Figure 3
Figure 3
Forest plot showing the mean difference in the FdQoL scores among the genotype categories within SNPs rs4680 and rs4818 when those randomized to OLP were compared to TAU. Brief description of methods [A complete description can be found in (29)].

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