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

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $657,319

## Abstract

PROJECT SUMMARY
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 mecha...

## Key facts

- **NIH application ID:** 10849676
- **Project number:** 5R01CA240417-05
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** JUN J MAO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $657,319
- **Award type:** 5
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10849676

## Citation

> US National Institutes of Health, RePORTER application 10849676, Effect and Mechanism of Acupuncture for Cancer-related Cognitive Impairment (ENHANCE) (5R01CA240417-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10849676. Licensed CC0.

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