Program Official

Principal Investigator

Jun J
Mao
Awardee Organization

Sloan-Kettering Inst Can Research
United States

Fiscal Year
2023
Activity Code
R01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Effect and Mechanism of Acupuncture for Cancer-related Cognitive Impairment (ENHANCE)

Cancer-related cognitive impairment (CRCI) is a devastating condition, affecting 3 in 4 breast cancer survivors. Non-pharmacologic interventions (e.g. exercise, cognitive training) demonstrated preliminary effects for CRCI, but their specific efficacies need to be confirmed in larger, rigorous trials using active/attention controls. More importantly, given the multi-faceted etiology and presentation of CRCI, it is unlikely that a single therapy is optimal for all patients; thus, there remains a critical need to test novel interventions and personalize treatment. Acupuncture has a growing evidence base in cancer symptom management, but its role in treating CRCI remains unclear. In animal models, acupuncture has been shown to modulate hippocampal expression of brain-derived neurotrophic factor (BDNF), an important cognitive biomarker. A Chinese study (N=80) found that acupuncture improved cognitive function and increased serum BDNF in breast cancer patients compared to usual care, but findings were limited by small sample size and lack of sham control, thus precluding evaluation of specific efficacy. In secondary analyses of our recent comparative effectiveness trial (N=160) of acupuncture versus cognitive-behavioral therapy for insomnia (CBT-I), acupuncture significantly improved subjective insomnia as well as perceived and objective cognitive functions, suggesting that targeting sleep improves cognition. Acupuncture also significantly increased serum BDNF, particularly among those with low baseline levels, whereas CBT-I did not. This suggests that BDNF is a specific mechanism by which acupuncture influences cognition and could help to identify individuals most likely to respond to acupuncture, thereby personalizing therapy. Based on this data, our central hypothesis is that acupuncture is an efficacious treatment for CRCI that works through a mechanism involving BDNF and sleep. Building on this work, we bring together a multi-disciplinary team to propose the Effect and Mechanism of Acupuncture for Cancer-related Cognitive Impairment (ENHANCE) trial. We found that nearly 80% of breast cancer survivors with CRCI report insomnia, echoing the growing research on connections between cognition and sleep. Thus, we will recruit 260 breast cancer survivors with CRCI and insomnia and randomize them to one of 3 conditions in an RCT: 1) acupuncture, 2) sham acupuncture (SA), or 3) usual-care wait-list control (WLC). We will collect serum BDNF and patient-reported/objective measures of cognition and sleep from baseline to Week 26. The Specific Aims are 1) to determine the effects of acupuncture on perceived CRCI and objective cognitive function; 2) to evaluate the mechanism of acupuncture on perceived CRCI and objective cognitive function via BDNF; and 3) to elucidate the role of insomnia on perceived CRCI and objective cognitive function in context of acupuncture. If successful, our study would expand treatment options for CRCI, advance mechanistic understanding of acupuncture, and disentangle the relationship between sleep and cognition, helping to shift the treatment paradigm towards a personalized model that targets CRCI phenotypes based on BDNF profile and insomnia.

Publications

  • Zhi WI, Baser RE, Talukder D, Mei YZ, Harte SE, Bao T. Mechanistic and thermal characterization of acupuncture for chemotherapy-induced peripheral neuropathy as measured by quantitative sensory testing. Breast cancer research and treatment. 2023 Feb;197(3):535-545. Epub 2022 Dec 17. PMID: 36527520
  • Bryl K, Chimonas S, Li X, Li SQ, Mao JJ. The relationship between anxiety and vaginal-related sexual health in postmenopausal breast cancer survivors on aromatase inhibitors therapies: a cross sectional study. Breast cancer research and treatment. 2023 Jul;200(2):257-264. Epub 2023 May 24. PMID: 37226019
  • Ulrich CM, Ratcliffe SJ, Zhou Q, Huang L, Hochheimer C, Gordon T, Knafl K, Miller V, Naylor MD, Schapira MM, Richmond TS, Grady C, Mao JJ. Association of Perceived Benefit or Burden of Research Participation With Participants' Withdrawal From Cancer Clinical Trials. JAMA network open. 2022 Nov 1;5(11):e2244412. PMID: 36449287
  • Yang M, Baser RE, Liou KT, Li SQ, Piulson L, Panageas KS, Mao JJ. Effect of acupuncture versus usual care on sleep quality in cancer survivors with chronic pain: Secondary analysis of a randomized clinical trial. Cancer. 2023 Jul 1;129(13):2084-2094. Epub 2023 Mar 29. PMID: 36989257
  • Bao T, Baser R, Chen C, Weitzman M, Zhang YL, Seluzicki C, Li QS, Piulson L, Zhi WI. Health-Related Quality of Life in Cancer Survivors with Chemotherapy-Induced Peripheral Neuropathy: A Randomized Clinical Trial. The oncologist. 2021 Nov;26(11):e2070-e2078. Epub 2021 Aug 26. PMID: 34390283
  • Li X, Mao JJ, Garland SN, Root J, Li SQ, Ahles T, Liou KT. Comparing sleep measures in cancer survivors: Self-reported sleep diary versus objective wearable sleep tracker. Research square. 2023 Oct 9. PMID: 37886444
  • Hung TKW, Latte-Naor S, Li Y, Kuperman GJ, Seluzicki C, Pendleton E, Pfister DG, Mao JJ. Assessment of Oncology Patient Engagement and Interest in Virtual Mind-Body Programming: Moving Toward Personalization of Virtual Care. JCO oncology practice. 2023 Feb;19(2):e185-e196. Epub 2022 Nov 18. PMID: 36399698
  • Yang M, Baser RE, Khanin R, Autuori I, Li QS, Panageas KS, Orlow I, Mao JJ. COMT Val158Met Affects the Analgesic Response to Acupuncture Among Cancer Survivors With Chronic Pain. The journal of pain. 2023 Sep;24(9):1721-1730. Epub 2023 May 13. PMID: 37187218
  • Bao T, Zhi WI, Baser RE, Li QS, Weitzman M, Gillespie EF, Robson M, Mao JJ. Electro-acupuncture versus battle field auricular acupuncture in breast cancer survivors with chronic musculoskeletal pain: subgroup analysis of a randomized clinical trial. Breast cancer research and treatment. 2023 Nov;202(2):287-295. Epub 2023 Aug 24. PMID: 37612534
  • Zhi WI, Baser RE, Zhi LM, Talukder D, Li QS, Paul T, Patterson C, Piulson L, Seluzicki C, Galantino ML, Bao T. Yoga for cancer survivors with chemotherapy-induced peripheral neuropathy: Health-related quality of life outcomes. Cancer medicine. 2021 Aug;10(16):5456-5465. Epub 2021 Jul 2. PMID: 34213086