Personalized electro-acupuncture versus auricular-acupuncture comparative effectiveness (PEACE): A protocol of a randomized controlled trial for chronic musculoskeletal pain in cancer survivors

Kevin T Liou, Ray Baser, Sally A D Romero, Jamie Green, Q Susan Li, Irene Orlow, Katherine S Panageas, Jun J Mao, Kevin T Liou, Ray Baser, Sally A D Romero, Jamie Green, Q Susan Li, Irene Orlow, Katherine S Panageas, Jun J Mao

Abstract

Introduction: Chronic pain is a leading cause of disability and remains under-treated in nearly half of patients with cancer. The opioid crisis has highlighted an urgent public health need for effective nonpharmacological pain management. Electroacupuncture (EA) and Battlefield Acupuncture (BFA) represent nonpharmacological modalities used in clinical practice to manage pain; however, their effectiveness has not been rigorously evaluated in oncology settings.

Methods: We describe the design of a 3-arm, parallel, single-center, multisite randomized controlled trial that investigates EA and BFA versus usual-care wait-list control (WLC) for chronic musculoskeletal pain among 360 patients with diverse cancer types across various stages. The primary aim is to compare effects of EA and BFA versus WLC on pain, physical function, and co-morbid symptoms. The secondary aim is to examine the interaction between patient outcome expectancy and acupuncture modality (EA vs BFA) on pain reduction. The tertiary aim is to evaluate the association between genetic polymorphisms and responses to acupuncture. Patients will be randomized in a 2:2:1 ratio to EA:BFA:WLC. Acupuncture groups will receive weekly treatments over 10 weeks. WLC will receive usual care over the same evaluation period as the acupuncture groups. The primary endpoint will be the change in average pain intensity score from baseline to week 12. We will collect validated patient-reported outcomes and blood/saliva samples at multiple timepoints over 24 weeks.

Discussion: Our findings will advance nonpharmacological pain management in oncology and inform personalized treatment approaches that integrate individuals' expectations and genetic biomarkers to deliver "precision" acupuncture to cancer patients with chronic pain.

Trial registration: ClinicalTrials.gov Identifier: NCT02979574.

Conflict of interest statement

The authors report no conflicts of interest.

Figures

Figure 1
Figure 1
Study Schema.

References

    1. Steglitz J, Buscemi J, Ferguson M. The future of pain research, education, and treatment: a summary of the IOM report “Relieving pain in America: a blueprint for transforming prevention, care, education, and research”. Behav Med Pract Policy Res 2012;2:6–8.
    1. Mao JJ, Armstrong K, Bowman MA, et al. Symptom burden among cancer survivors: impact of age and comorbidity. J Am Board Fam Med 2007;20:434–43.
    1. Deandrea S, Montanari M, Moja L, et al. Prevalence of undertreatment in cancer pain. A review of published literature. Ann Oncol 2008;19:1985–91.
    1. van den Beuken-van Everdingen MH, Hochstenbach LM, Joosten EA, et al. Update on prevalence of pain in patients with cancer: systematic review and meta-analysis. J Pain Symptom Manage 2016;51:1070–90. e1079.
    1. Zylla D, Steele G, Gupta P. A systematic review of the impact of pain on overall survival in patients with cancer. Support Care Cancer 2017;25:1687–98.
    1. Paice JA. Navigating cancer pain management in the midst of the opioid epidemic. Oncology (Williston Park, NY) 2018;32:386–90. 403.
    1. Weeks J. Influential U.S. Medical Organizations call for insurance coverage of non-pharmacologic approaches to pain. J Altern Complement Med 2016;22:947–9.
    1. Mao JJ, Kapur R. Acupuncture in primary care. Prim Care 2010;37:105–17.
    1. White A. A cumulative review of the range and incidence of significant adverse events associated with acupuncture. Acupunct Med 2004;22:122–33.
    1. Witt CM, Pach D, Brinkhaus B, et al. Safety of acupuncture: results of a prospective observational study with 229,230 patients and introduction of a medical information and consent form. Forsch Komplementarmed 2009;16:91–7.
    1. Aloe L, Manni L. Low-frequency electro-acupuncture reduces the nociceptive response and the pain mediator enhancement induced by nerve growth factor. Neurosci Lett 2009;449:173–7.
    1. Lee HJ, Lee JH, Lee EO, et al. Substance P and beta-endorphin mediate electro-acupuncture induced analgesia in mouse cancer pain model. J Exp Clin Cancer Res 2009;28:102.
    1. Zhang RX, Wang L, Wang X, et al. Electroacupuncture combined with MK-801 prolongs anti-hyperalgesia in rats with peripheral inflammation. Pharmacol Biochem Behav 2005;81:146–51.
    1. Huang W, Pach D, Napadow V, et al. Characterizing acupuncture stimuli using brain imaging with FMRI--a systematic review and meta-analysis of the literature. PLoS One 2012;7:e32960.
    1. He Y, Guo X, May BH, et al. Clinical evidence for association of acupuncture and acupressure with improved cancer pain: a systematic review and meta-analysis. JAMA Oncol 2019.
    1. Han JS. Acupuncture: neuropeptide release produced by electrical stimulation of different frequencies. Trends Neurosci 2003;26:17–22.
    1. Vickers AJ, Cronin AM, Maschino AC, et al. Acupuncture for chronic pain: individual patient data meta-analysis. Arch Intern Med 2012;172:1444–53.
    1. Vickers AJ, Vertosick EA, Lewith G, et al. Acupuncture for chronic pain: update of an individual patient data meta-analysis. J Pain 2018;19:455–74.
    1. Zia FZ, Olaku O, Bao T, et al. The National Cancer Institute's Conference on Acupuncture for Symptom Management in Oncology: State of the Science, Evidence, and Research Gaps. J Natl Cancer Inst Monogr 2017;2017:
    1. Niemtzow R. Battlefield acupuncture. Med Acupunct 2007;19:
    1. Federman DG, Zeliadt SB, Thomas ER, et al. Battlefield acupuncture in the Veterans Health Administration: effectiveness in individual and group settings for pain and pain comorbidities. Med Acupunct 2018;30:273–8.
    1. Fox LM, Murakami M, Danesh H, et al. Battlefield acupuncture to treat low back pain in the emergency department. Am J Emerg Med 2018;36:1045–8.
    1. Goertz CM, Niemtzow R, Burns SM, et al. Auricular acupuncture in the treatment of acute pain syndromes: a pilot study. Mil Med 2006;171:1010–4.
    1. Niemtzow R, Baxter J, Gallagher RM, et al. Building capacity for complementary and integrative medicine through a large, cross-agency, acupuncture training program: lessons learned from a Military Health System and Veterans Health Administration Joint Initiative Project. Mil Med 2018;183:e486–93.
    1. Taylor SL, Giannitrapani K, Ackland PE, et al. Challenges and Strategies for implementing Battlefield Acupuncture in the veterans administration: a qualitative study of provider perspectives. Med Acupunct 2018;30:252–61.
    1. Hui D, Bruera E. A personalized approach to assessing and managing pain in patients with cancer. J Clin Oncol 2014;32:1640–6.
    1. Boutron I, Moher D, Altman DG, et al. Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. Ann Intern Med 2008;148:295–309.
    1. MacPherson H, Altman DG, Hammerschlag R, et al. Revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): extending the CONSORT statement. PLoS Med 2010;7:e1000261.
    1. Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377–81.
    1. Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singapore 1994;23:129–38.
    1. Farrar JT, Young JP, Jr, LaMoreaux L, et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94:149–58.
    1. Osman A, Barrios FX, Kopper BA, et al. Factor structure, reliability, and validity of the Pain Catastrophizing Scale. J Behav Med 1997;20:589–605.
    1. Sloan JA, Aaronson N, Cappelleri JC, et al. Clinical Significance Consensus Meeting Group. Assessing the clinical significance of single items relative to summated scores. Mayo Clin Proc 2002;77:479–87.
    1. Reinhold T, Brinkhaus B, Willich SN, et al. Acupuncture in patients suffering from allergic asthma: is it worth additional costs? J Altern Complement Med (New York, NY) 2014;20:169–77.
    1. Willich SN, Reinhold T, Selim D, et al. Cost-effectiveness of acupuncture treatment in patients with chronic neck pain. Pain 2006;125:107–13.
    1. Revicki DA, Kawata AK, Harnam N, et al. Predicting EuroQol (EQ-5D) scores from the patient-reported outcomes measurement information system (PROMIS) global items and domain item banks in a United States sample. Qual Life Res 2009;18:783–91.
    1. McConnell S, Kolopack P, Davis AM. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC): a review of its utility and measurement properties. Arthritis Rheum 2001;45:453–61.
    1. Gummesson C, Ward MM, Atroshi I. The shortened disabilities of the arm, shoulder and hand questionnaire (QuickDASH): validity and reliability based on responses within the full-length DASH. BMC Musculoskelet Disord 2006;7:44.
    1. LeBlanc M, Stineman M, DeMichele A, et al. Validation of QuickDASH outcome measure in breast cancer survivors for upper extremity disability. Arch Phys Med Rehabil 2014;95:493–8.
    1. Mao JJ, Farrar JT, Bruner D, et al. Electroacupuncture for fatigue, sleep, and psychological distress in breast cancer patients with aromatase inhibitor-related arthralgia: a randomized trial. Cancer 2014;120:3744–51.
    1. Mendoza TR, Wang XS, Cleeland CS, et al. The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory. Cancer 1999;85:1186–96.
    1. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361–70.
    1. Weathers F, Ford J. Stamm BH. Psychometric review of PTSD checklist (PCP-C, PCL-S, PCL-M, PCL-PR). Measurement of Stress, Trauma, and Adaptation Lutherville. MD: Sidran Press; 1996. 250–2.
    1. Buysse DJ, Reynolds CF, 3rd, Monk TH, et al. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28:193–213.
    1. Smith AB, Selby PJ, Velikova G, et al. Factor analysis of the Hospital Anxiety and Depression Scale from a large cancer population. Psychol Psychother 2002;75(Pt 2):165–76.
    1. Ruggiero KJ, Del Ben K, Scotti JR, et al. Psychometric properties of the PTSD Checklist-Civilian Version. J Trauma Stress 2003;16:495–502.
    1. Mollayeva T, Thurairajah P, Burton K, et al. The Pittsburgh sleep quality index as a screening tool for sleep dysfunction in clinical and non-clinical samples: a systematic review and meta-analysis. Sleep Med Rev 2016;25:52–73.
    1. Hays RD, Bjorner JB, Revicki DA, et al. Development of physical and mental health summary scores from the patient-reported outcomes measurement information system (PROMIS) global items. Qual Life Res 2009;18:873–80.
    1. Colagiuri B, Smith CA. A systematic review of the effect of expectancy on treatment responses to acupuncture. Evid Based Complement Alternat Med 2012;2012:857804.
    1. Mao JJ, Xie SX, Bowman MA. Uncovering the expectancy effect: the validation of the acupuncture expectancy scale. Altern Ther Health Med 2011;16:22–7.
    1. Mao JJ, Armstrong K, Farrar JT, et al. Acupuncture expectancy scale: development and preliminary validation in China. Explore (NY) 2007;3:372–7.
    1. Diatchenko L, Slade GD, Nackley AG, et al. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet 2005;14:135–43.
    1. De Gregori M, Garbin G, De Gregori S, et al. Genetic variability at COMT but not at OPRM1 and UGT2B7 loci modulates morphine analgesic response in acute postoperative pain. Eur J Clin Pharmacol 2013;69:1651–8.
    1. Genovese TJ, Mao JJ. Genetic predictors of response to acupuncture for aromatase inhibitor-associated arthralgia among breast cancer survivors. Pain Med (Malden, Mass) 2019;20:191–4.
    1. Hall KT, Lembo AJ, Kirsch I, et al. Catechol-O-Methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome. PLoS One 2012;7:e48135.
    1. Takeshige C, Tsuchiya M, Guo SY, et al. Dopaminergic transmission in the hypothalamic arcuate nucleus to produce acupuncture analgesia in correlation with the pituitary gland. Brain Res Bull 1991;26:113–22.
    1. Kim MR, Kim SJ, Lyu YS, et al. Effect of acupuncture on behavioral hyperactivity and dopamine release in the nucleus accumbens in rats sensitized to morphine. Neurosci Lett 2005;387:17–21.
    1. Hui KK, Liu J, Marina O, et al. The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 as evidenced by fMRI. Neuroimage 2005;27:479–96.
    1. Napadow V, Makris N, Liu J, et al. Effects of electroacupuncture versus manual acupuncture on the human brain as measured by fMRI. Hum Brain Mapp 2005;24:193–205.
    1. Ingle JN, Schaid DJ, Goss PE, et al. Genome-wide associations and functional genomic studies of musculoskeletal adverse events in women receiving aromatase inhibitors. J Clin Oncol 2010;28:4674–82.
    1. Liu M, Wang L, Bongartz T, et al. Aromatase inhibitors, estrogens and musculoskeletal pain: estrogen-dependent T-cell leukemia 1A (TCL1A) gene-mediated regulation of cytokine expression. Breast Cancer Res 2012;14:R41.
    1. Correa DD, Satagopan J, Cheung K, et al. COMT, BDNF, and DTNBP1 polymorphisms and cognitive functions in patients with brain tumors. Neuro Oncol 2016;18:1425–33.
    1. Orlow I, Satagopan JM, Berwick M, et al. Genetic factors associated with naevus count and dermoscopic patterns: preliminary results from the Study of Nevi in Children (SONIC). Br J Dermatol 2015;172:1081–9.
    1. Orlow I, Shi Y, Kanetsky PA, et al. The interaction between vitamin D receptor polymorphisms and sun exposure around time of diagnosis influences melanoma survival. Pigment Cell Melanoma Res 2018;31:287–96.
    1. Mao JJ, Xie SX, Farrar JT, et al. A randomised trial of electro-acupuncture for arthralgia related to aromatase inhibitor use. Eur J Cancer 2014;50:267–76.
    1. Cheng X. Foreign Languages Press, Chinese Acupuncture and Moxibustion. Beijing, China: 1987.
    1. Mao JJ, Farrar JT, Armstrong K, et al. De qi: Chinese acupuncture patients’ experiences and beliefs regarding acupuncture needling sensation—an exploratory survey. Acupunct Med 2007;25:158–65.
    1. Dmitrienko A, Millen BA, Brechenmacher T, et al. Development of gatekeeping strategies in confirmatory clinical trials. Biom J 2011;53:875–93.
    1. Laird NM, Ware JH. Random-effects models for longitudinal data. Biometrics 1982;38:963–74.
    1. Liu GF, Lu K, Mogg R, et al. Should baseline be a covariate or dependent variable in analyses of change from baseline in clinical trials? Stat Med 2009;28:2509–30.
    1. Bauml J, Xie SX, Farrar JT, et al. Expectancy in real and sham electroacupuncture: does believing make it so? J Natl Cancer Inst Monogr 2014;2014:302–7.
    1. Lu K, Luo X, Chen PY. Sample size estimation for repeated measures analysis in randomized clinical trials with missing data. Int J Biostat 2008;4: Article 9.
    1. Vadivelu N, Kai AM, Kodumudi V, et al. The opioid crisis: a comprehensive overview. Curr Pain headache Rep 2018;22:16.
    1. Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin 2016;66:271–89.
    1. Yun H, Sun L, Mao JJ. Growth of integrative medicine at leading cancer centers between 2009 and 2016: a systematic analysis of NCI-designated comprehensive cancer center websites. J Natl Cancer Inst Monogr 2017;2017:
    1. Mao JJ, Palmer CS, Healy KE, et al. Complementary and alternative medicine use among cancer survivors: a population-based study. J Cancer Surviv 2011;5:8–17.
    1. Lu W, Dean-Clower E, Doherty-Gilman A, et al. The value of acupuncture in cancer care. Hematol Oncol Clin North Am 2008;22:631–48. viii.
    1. MacPherson H, Vertosick EA, Foster NE, et al. The persistence of the effects of acupuncture after a course of treatment: a meta-analysis of patients with chronic pain. Pain 2017;158:784–93.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться