Chemo-brainNCT02457039
Acupuncture Prevents Chemobrain in Breast Cancer Patients
A study testing Dense cranial electroacupuncture stimulation, Body acupuncture and Least acupuncture stimulation in people with Chemo-brain and Drug-Related Side Effects and Adverse Reactions, run by The University of Hong Kong at 6 sites in 2 countries.
Trial summary
Chemobrain is an expression used to describe a cluster of chemotherapy-induced cognitive impairment symptoms, including problems with visual and verbal memory, forgetfulness, difficulty in learning, attention, concentration and coordination of multitasking and organization. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Chemo-brain, Drug-Related Side Effects and Adverse Reactions, Mild Cognitive Impairment
- What is being tested?
- Dense cranial electroacupuncture stimulation, Body acupuncture and Least acupuncture stimulation
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 93 participants
- Where
- 6 sitesin 2 countries
- Study dates
- Oct 2015to Mar 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chinese females aged 18 to 65 years;
- have a diagnosis of stage I-IIIa breast cancer; and
- are ready for orally administered or vein injection or both with Cytoxan-containing regimens as adjuvant chemotherapy before or after surgical treatment or in combination with other pharmacotherapy.
Who cannot join
- had chemotherapy in the last 2 years;
- have cardiac pacemakers, epilepsy or other unstable medical conditions;
- had investigational drug treatment within the past 6 months;
- alcoholism or drug abuse within the past 1 year; or
- have severe needle phobia.
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
Hong Kong4 sites
Department of Clinical Oncology, Queen Mary Hospital
Hong Kong
Department of Surgery, Queen Mary Hospital
Hong Kong
Department of Surgery, Tung Wah Hospital
Sai Ying Pun
The Nethersole School of Nursing, The Chinese University of Hong Kong
Shatin, N.T.
China2 sites
Department of Chinese Medicine, The University of Hong Kong - Shenzhen Hospital
Shenzhen, Guangdong, 518053
Department of Clinical Oncology, The University of Hong Kong - Shenzhen Hospital
Shenzhen, Guangdong, 518053
About this study
Official title: An Assessor-Blinded, Randomised Controlled Trial of Acupuncture to Prevent Chemobrain in Breast Cancer Patients
Chemobrain is an expression used to describe a cluster of chemotherapy-induced cognitive impairment symptoms, including problems with visual and verbal memory, forgetfulness, difficulty in learning, attention, concentration and coordination of multitasking and organization. Over 75% cancer patients experienced acute cognitive symptoms during chemotherapy and 17%-34% of them have long-term post-treatment cognitive deficits which can persist up to 10 years. Breast cancer survivors even display as high as 50%-75% prevalence of post-treatment cognitive impairment. Chemobrain has become an apparent quality-of-life issue for cancer survivors and will be encountered more frequently with the rise of the number of cancer survivors. There are no effective interventions available for preventing and treating chemobrain.
Acupuncture is beneficial in reducing various side effects of anti-cancer treatment. It also shows the efficacy in improving mild cognitive impairment and other dementia disorders; facilitates the recovery of pathological microstructural changes of the brain. These results have led to the hypothesis that acupuncture is effective in preventing chemobrain and this preventive effect may be associated with the protection against cytokine production, epigenetic modification and microstructural changes of the brain.
Read more
To test this hypothesis, an assessor-blinded, randomised controlled trial will be conducted to determine if a combination of DCEAS and body acupuncture could reduce the incidence and symptoms of chemobrain in breast cancer patients under chemotherapy compared to least acupuncture stimulation (LAS) as controls.
A total of 168 breast cancer patients who are ready for chemotherapy will be randomly assigned to comprehensive acupuncture intervention (combined DCEAS and body acupuncture regimen + chemotherapy) (CAI) (n = 84) for 2 sessions per week for 8 weeks or least acupuncture stimulation (LAS) (minimal acupuncture + chemotherapy) (n = 84). All patients receive the standard chemotherapy of breast cancer. Treatment outcomes on cognitive performance, fatigue and the depression will be assessed.
Read the detailed description
Although the development of various chemotherapeutic drugs has greatly improved clinical outcomes and survival rate of cancer patients, it also causes various adverse side effects. Chemotherapy-induced cognitive impairment, often referred to as chemobrain, has drawn increasing attention due to the rise in the number of cancer survivors over the past decade. Numerous studies have shown that chemotherapy can cause acute and long-term post-treatment cognitive impairment, including problems with visual and verbal memory, forgetfulness, difficulty in learning, attention, concentration and coordination of multitasking and organization. Over 75% cancer patients reported to experience acute cognitive symptoms during chemotherapy and 17%-34% of them have long-term post-treatment cognitive deficits which can persist up to 10 years. Breast cancer survivors may display higher prevalence of post-treatment cognitive impairment. The severity of reported chemobrain symptoms is variable, from subtle to more severe. Chemobrain has become an apparent quality-of-life issue for survivors and will be encountered more frequency in the future. However, there are no effective interventions available to prevent and treat chemobrain, although some pharmacological, antioxidant and various cognitive approaches have been tested.
It is believed that chemobrain is a consequence of brain neuronal injury induced by systemically administered chemotherapeutic agents via direct and indirect mechanisms, resulting in the suppression of neuronal cell proliferation, epigenetic modification and microstructural changes of the brain. These pathological circumstances are largely developed from alternations in cytokine milieu. While physical and psychological stressors that cancer patients experienced after diagnosis, chemotherapy and long-term follow-up have been shown to increase circulating cytokine levels and increased cytokine levels are associated with cognitive decline in cancer patients, the administration of chemotherapy also results in cytokine production at peripheral and central levels as the medications induce tumor cell death and collateral tissue injury. Patients undergoing chemotherapy have been found to display significant increases in multiple cytokines.
A large body of evidence well confirms that acupuncture is effective in reducing anti-cancer treatment-caused side effects, including pain, nausea, hot flashes, fatigue, xerostomia, anxiety, depression and sleep disturbance. Numerous studies further have shown the effectiveness of acupuncture therapy in improving cognitive function of patients with mild cognitive impairment (MCI) and various dementia. The reduced severity of cognitive symptoms is associated with neuroimaging improvement in brain regions associated with learning and memory process. Acupuncture also ameliorates cognitive impairment in various animal models. Studies have further revealed that the cognition-improving effects of acupuncture are associated with the inhibition of cytokine-mediated neuronal cell apoptosis, inflammatory reaction and oxidative cellular injury and the effects in reducing cognitive symptoms are related to the protection of neuronal cells, improvement of electrophysiological activities of the hippocampus and brain cell proliferation. Moreover, acupuncture also displays a significant effect in facilitating the recovery of the brain at microstructural histopathological level in patients with cerebral infarction and in rats with transient focal cerebral ischemia. The investigators therefore hypothesize that acupuncture may be also effective in preventing and reducing chemotherapy caused cognitive impairment.
Recently, the investigators have developed a novel acupuncture stimulation called dense cranial electroacupuncture stimulation (DCEAS) on the basis of neuroanatomical rationale. In this mode, electrical stimulation is delivered on dense acupoints located on the forehead innervated by the trigeminal nerve. The trigeminal sensory pathway has much intimate fiber connections with brain regions associated with sensory, locomotor, visceral function, sleep, emotion, learning and memory. Therefore, DCEAS can effectively modulate brain functions. Over the past 5 years, the investigators have completed several clinical studies and demonstrated the benefits of DCEAS in the treatment of major depression, insomnia, OCD, postpartum depression and post-stroke depression. In the proposed study, a combination of DCEAS and body acupuncture will be employed to prevent and treat chemobrain in breast cancer patients.
- Conditions
- Chemo-brain, Drug-Related Side Effects and Adverse Reactions, Mild Cognitive Impairment, Breast Cancer
- Being tested
- Dense cranial electroacupuncture stimulation, Body acupuncture, Least acupuncture stimulation, Cytoxan-containing chemotherapy regimens
- Keywords
- Chemo-brain, Drug-Related Side Effects and Adverse Reactions, Mild Cognitive Impairment, Breast cancer
- Medical subject headings
- Drug-Related Side Effects and Adverse Reactions, Cognitive Dysfunction, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dense cranial electroacupuncture stimulationProcedure or surgery
Also called DCEAS
DCEAS is a is a novel stimulation mode in which electrical stimulation is delivered on acupoints located on the forehead.
Six pairs of acupoints are used: Baihui (GV20) and Yintang (EX-HN3), left Sishencong (EX-HN1) and Toulinqi (GB15), right Sishencong (EX-HN1) and Toulinqi (GB15), bilateral Shuaigu (GB8), bilateral Taiyang (EX-HN5), and bilateral Touwei (ST8).
Disposable acupuncture needles (Hwato®, 0.30 mm in diameter and 25-40 mm in length) are inserted at a depth of 10-30 mm perpendicularly or obliquely into acupoints. Manual manipulation is then conducted to evoke needling sensation, followed by electrical stimulation (ITO ES-160, continuous waves at 2 Hz).
Body acupunctureProcedure or surgery
Also called BA
Following acupoints are used: Shui-Gou (GV26), Shen-Men (HT7). He-Gu (LI4), Wai-Guan (TE5), Zhong-Wan (CV12), Guan-Yuan (CV4), Zu-San-Li (ST36), Feng-Long (ST40) and San-Yin-Jiao (SP6).
Disposable acupuncture needles (Hwato®, 0.30 mm in diameter and 25-40 mm in length) are inserted at a depth of 10-30 mm perpendicularly or obliquely into acupoints. Manual manipulation is then conducted to evoke needling sensation. No electrical stimulation is delivered.
Least acupuncture stimulationProcedure or surgery
Also called LAS
The acupoints chosen are less related to the treated syndromes based on Traditional Chinese Medicine (TCM) theory; the number of acupoints used and the intensity of electrical stimulation are also lower than the comprehensive acupuncture regimen. The following 6 acupoints will be used in LAS control: bilateral Tong-Tian (GB17), bilateral Shou San-Li (LI10) and bilateral Fu-Yang (BL59). Electrical stimulation will be only performed on bilateral Tong-Tian (GB17) and the intensities are adjusted to a level at which patients just start feeling the stimulation.
Cytoxan-containing chemotherapy regimensDrug
Also called Chemo
Each subject shall receive oral administration or venous injection or both with adjuvant or neoadujuvant chemotherapy regimens, as decided by clinical oncologist.
In clinical practice, the most commonly used Cytoxan-containing regimens include but are not limit to:
AC (x4) [Adriamycin + Cytoxan], TC (x4) [Taxotere + Cytoxan], AC-P (4+4) [Adriamycin + Cytoxan + Paclitaxel], TAC (x6) [Taxotere + Adriamycin + Cytoxan], or AC-PH (4+4) [Adriamycin + Cytoxan + Paclitaxel + Herceptin].
| Study group | Role | What they receive |
|---|---|---|
| Comprehensive acupuncture (CAI) | Active comparator | Breast cancer patients receiving Cytoxan-containing chemotherapy regimens (Chemo) will receive Dense cranial electroacupuncture stimulation (DCEAS) and Body acupuncture (BA). Receives: Procedure: Dense cranial electroacupuncture stimulation; Procedure: Body acupuncture; Drug: Cytoxan-containing chemotherapy regimens |
| Least acupuncture stimulation (LAS) | Sham comparator | Breast cancer patients receiving Cytoxan-containing chemotherapy regimens (Chemo) will receive Least acupuncture stimulation (LAS) Receives: Procedure: Least acupuncture stimulation; Drug: Cytoxan-containing chemotherapy regimens |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in cognitive function (objective measurement)
The Montreal Cognitive Assessment (MoCA) of corresponding dialects will be used as an objective measurement for subjects' cognitive function. Assessments will be conducted at baseline and every 2 weeks thereafter.
Measured: Baseline, 2 week, 4 week, 6 week, 8 week
Changes in cognitive function (subjective measurement)
The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) of corresponding dialects will be used as a subjective measurement for subjects' cognitive function. Assessments will be conducted at baseline and every 2 weeks thereafter.
Measured: Baseline, 2 week, 4 week, 6 week, 8 week
Secondary outcomes (4)
Changes in quality of Life - composite measure
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30+BR23) and Functional Assessment of Cancer Therapy-Breast (FACT-B) of corresponding dialects will be used for assessment on quality of life. Both of them will be used as the former focuses on physical function, while the latter emphasizes on emotional well-being. Assessments will be conducted at baseline and every 4 weeks thereafter.
Measured: Baseline, 4 week, 8 week
Changes in illness related fatigue measured by FACIT-Fatigue
As fatigue is a common co-morbidity observed in patients receiving chemotherapy, it will be measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) of corresponding dialects. Assessments will be conducted at baseline and every 4 weeks thereafter.
Measured: Baseline, 4 week, 8 week
Changes in chemo adverse effects - composite measure
Adverse side effects will be assessed using Functional Assessment of Cancer Therapy questionnaires (FACT-Taxane, FACT-BRM) of corresponding dialects. Assessments will be conducted at baseline and every 4 weeks thereafter.
Measured: Baseline, 4 week, 8 week
Changes in subject perception of chemotherapy treatment measured by FACIT-TS-G
To determine whether acupuncture can reduce the adverse effects of chemo-therapy treatment and therefore increase subject acceptance, subject treatment satisfaction will be assessed using Functional Assessment of Chronic Illness Therapy questionnaire (FACIT-TS-G). Assessments will be conducted at baseline and every 4 weeks thereafter.
Measured: Baseline, 4 week, 8 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2015 (estimated)
- Study startOct 2015
- Primary completionDec 2018
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (40)Papers the sponsor has linked to this study.
- Other trials for Chemo-brainStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- Chinese University of Hong Kong
- Responsible party
- Principal investigator, Prof. Zhang Zhang-Jin, The University of Hong Kong
- Investigators
- Zhang-Jin ZHANG, MMed, PhD, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02457039
- Sponsor's protocol ID
- UW 14-206
- Status last verified
- May 2019
- First submitted
- 15 May 2015
- Last updated
- 20 May 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Nelson CJ, Nandy N, Roth AJ. Chemotherapy and cognitive deficits: mechanisms, findings, and potential interventions. Palliat Support Care. 2007 Sep;5(3):273-80. doi: 10.1017/s1478951507000442.
PubMed 17969831Asher A. Cognitive dysfunction among cancer survivors. Am J Phys Med Rehabil. 2011 May;90(5 Suppl 1):S16-26. doi: 10.1097/PHM.0b013e31820be463.
PubMed 21765260Hede K. Chemobrain is real but may need new name. J Natl Cancer Inst. 2008 Feb 6;100(3):162-3, 169. doi: 10.1093/jnci/djn007. Epub 2008 Jan 29. No abstract available.
PubMed 18230787Matsuda T, Takayama T, Tashiro M, Nakamura Y, Ohashi Y, Shimozuma K. Mild cognitive impairment after adjuvant chemotherapy in breast cancer patients--evaluation of appropriate research design and methodology to measure symptoms. Breast Cancer. 2005;12(4):279-87. doi: 10.2325/jbcs.12.279.
PubMed 16286908Avisar A, River Y, Schiff E, Bar-Sela G, Steiner M, Ben-Arye E. Chemotherapy-related cognitive impairment: does integrating complementary medicine have something to add? Review of the literature. Breast Cancer Res Treat. 2012 Nov;136(1):1-7. doi: 10.1007/s10549-012-2211-5. Epub 2012 Aug 23.
PubMed 22915072Briones TL, Woods J. Chemotherapy-induced cognitive impairment is associated with decreases in cell proliferation and histone modifications. BMC Neurosci. 2011 Dec 9;12:124. doi: 10.1186/1471-2202-12-124.
PubMed 22152030Simo M, Rifa-Ros X, Rodriguez-Fornells A, Bruna J. Chemobrain: a systematic review of structural and functional neuroimaging studies. Neurosci Biobehav Rev. 2013 Sep;37(8):1311-21. doi: 10.1016/j.neubiorev.2013.04.015. Epub 2013 May 6.
PubMed 23660455Garcia MK, McQuade J, Haddad R, Patel S, Lee R, Yang P, Palmer JL, Cohen L. Systematic review of acupuncture in cancer care: a synthesis of the evidence. J Clin Oncol. 2013 Mar 1;31(7):952-60. doi: 10.1200/JCO.2012.43.5818. Epub 2013 Jan 22.
PubMed 23341529Chou P, Chu H, Lin JG. Effects of electroacupuncture treatment on impaired cognition and quality of life in Taiwanese stroke patients. J Altern Complement Med. 2009 Oct;15(10):1067-1073.
PubMed 20050300Guo Y, Shi X, Uchiyama H, Hasegawa A, Nakagawa Y, Tanaka M, Fukumoto I. A study on the rehabilitation of cognitive function and short-term memory in patients with Alzheimer's disease using transcutaneous electrical nerve stimulation. Front Med Biol Eng. 2002;11(4):237-47. doi: 10.1163/156855701321138905.
PubMed 12735425Yu J, Zhang X, Liu C, Meng Y, Han J. Effect of acupuncture treatment on vascular dementia. Neurol Res. 2006 Jan;28(1):97-103. doi: 10.1179/016164106X91951.
PubMed 16464371Zhao L, Zhang H, Zheng Z, Huang J. Electroacupuncture on the head points for improving gnosia in patients with vascular dementia. J Tradit Chin Med. 2009 Mar;29(1):29-34. doi: 10.1016/s0254-6272(09)60027-3.
PubMed 19514185Zhou Y, Jin J. Effect of acupuncture given at the HT 7, ST 36, ST 40 and KI 3 acupoints on various parts of the brains of Alzheimer' s disease patients. Acupunct Electrother Res. 2008;33(1-2):9-17.
PubMed 18672741Manni L, Aloe L, Fiore M. Changes in cognition induced by social isolation in the mouse are restored by electro-acupuncture. Physiol Behav. 2009 Dec 7;98(5):537-42. doi: 10.1016/j.physbeh.2009.08.011. Epub 2009 Sep 3.
PubMed 19733189Yu J, Liu C, Zhang X, Han J. Acupuncture improved cognitive impairment caused by multi-infarct dementia in rats. Physiol Behav. 2005 Nov 15;86(4):434-41. doi: 10.1016/j.physbeh.2005.07.015. Epub 2005 Sep 21.
PubMed 16181648
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Assessor-Blinded, Randomised Controlled Trial of Acupuncture to Prevent Chemobrain in Breast Cancer Patients
- ClinicalTrials.gov ID
- NCT02457039
- Acronym / sponsor ID
- UW 14-206
- Conditions
- Chemo-brain, Drug-Related Side Effects and Adverse Reactions, Mild Cognitive Impairment, Breast Cancer
- Keywords
- Chemo-brain, Drug-Related Side Effects and Adverse Reactions, Mild Cognitive Impairment, Breast cancer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Collaborators
- Chinese University of Hong Kong
- Study start
- Oct 2015 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 29 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chemobrain is an expression used to describe a cluster of chemotherapy-induced cognitive impairment symptoms, including problems with visual and verbal memory, forgetfulness, difficulty in learning, attention, concentration and coordination of multitasking and organization. Over 75% cancer patients experienced acute cognitive symptoms during chemotherapy and 17%-34% of them have long-term post-treatment cognitive deficits which can persist up to 10 years. Breast cancer survivors even display as high as 50%-75% prevalence of post-treatment cognitive impairment. Chemobrain has become an apparent quality-of-life issue for cancer survivors and will be encountered more frequently with the rise of the number of cancer survivors. There are no effective interventions available for preventing and treating chemobrain.
Acupuncture is beneficial in reducing various side effects of anti-cancer treatment. It also shows the efficacy in improving mild cognitive impairment and other dementia disorders; facilitates the recovery of pathological microstructural changes of the brain. These results have led to the hypothesis that acupuncture is effective in preventing chemobrain and this preventive effect may be associated with the protection against cytokine production, epigenetic modification and microstructural changes of the brain.
To test this hypothesis, an assessor-blinded, randomised controlled trial will be conducted to determine if a combination of DCEAS and body acupuncture could reduce the incidence and symptoms of chemobrain in breast cancer patients under chemotherapy compared to least acupuncture stimulation (LAS) as controls.
A total of 168 breast cancer patients who are ready for chemotherapy will be randomly assigned to comprehensive acupuncture intervention (combined DCEAS and body acupuncture regimen + chemotherapy) (CAI) (n = 84) for 2 sessions per week for 8 weeks or least acupuncture stimulation (LAS) (minimal acupuncture + chemotherapy) (n = 84). All patients receive the standard chemotherapy of breast cancer. Treatment outcomes on cognitive performance, fatigue and the depression will be assessed.
Detailed description
Although the development of various chemotherapeutic drugs has greatly improved clinical outcomes and survival rate of cancer patients, it also causes various adverse side effects. Chemotherapy-induced cognitive impairment, often referred to as chemobrain, has drawn increasing attention due to the rise in the number of cancer survivors over the past decade. Numerous studies have shown that chemotherapy can cause acute and long-term post-treatment cognitive impairment, including problems with visual and verbal memory, forgetfulness, difficulty in learning, attention, concentration and coordination of multitasking and organization. Over 75% cancer patients reported to experience acute cognitive symptoms during chemotherapy and 17%-34% of them have long-term post-treatment cognitive deficits which can persist up to 10 years. Breast cancer survivors may display higher prevalence of post-treatment cognitive impairment. The severity of reported chemobrain symptoms is variable, from subtle to more severe. Chemobrain has become an apparent quality-of-life issue for survivors and will be encountered more frequency in the future. However, there are no effective interventions available to prevent and treat chemobrain, although some pharmacological, antioxidant and various cognitive approaches have been tested.
It is believed that chemobrain is a consequence of brain neuronal injury induced by systemically administered chemotherapeutic agents via direct and indirect mechanisms, resulting in the suppression of neuronal cell proliferation, epigenetic modification and microstructural changes of the brain. These pathological circumstances are largely developed from alternations in cytokine milieu. While physical and psychological stressors that cancer patients experienced after diagnosis, chemotherapy and long-term follow-up have been shown to increase circulating cytokine levels and increased cytokine levels are associated with cognitive decline in cancer patients, the administration of chemotherapy also results in cytokine production at peripheral and central levels as the medications induce tumor cell death and collateral tissue injury. Patients undergoing chemotherapy have been found to display significant increases in multiple cytokines.
A large body of evidence well confirms that acupuncture is effective in reducing anti-cancer treatment-caused side effects, including pain, nausea, hot flashes, fatigue, xerostomia, anxiety, depression and sleep disturbance. Numerous studies further have shown the effectiveness of acupuncture therapy in improving cognitive function of patients with mild cognitive impairment (MCI) and various dementia. The reduced severity of cognitive symptoms is associated with neuroimaging improvement in brain regions associated with learning and memory process. Acupuncture also ameliorates cognitive impairment in various animal models. Studies have further revealed that the cognition-improving effects of acupuncture are associated with the inhibition of cytokine-mediated neuronal cell apoptosis, inflammatory reaction and oxidative cellular injury and the effects in reducing cognitive symptoms are related to the protection of neuronal cells, improvement of electrophysiological activities of the hippocampus and brain cell proliferation. Moreover, acupuncture also displays a significant effect in facilitating the recovery of the brain at microstructural histopathological level in patients with cerebral infarction and in rats with transient focal cerebral ischemia. The investigators therefore hypothesize that acupuncture may be also effective in preventing and reducing chemotherapy caused cognitive impairment.
Recently, the investigators have developed a novel acupuncture stimulation called dense cranial electroacupuncture stimulation (DCEAS) on the basis of neuroanatomical rationale. In this mode, electrical stimulation is delivered on dense acupoints located on the forehead innervated by the trigeminal nerve. The trigeminal sensory pathway has much intimate fiber connections with brain regions associated with sensory, locomotor, visceral function, sleep, emotion, learning and memory. Therefore, DCEAS can effectively modulate brain functions. Over the past 5 years, the investigators have completed several clinical studies and demonstrated the benefits of DCEAS in the treatment of major depression, insomnia, OCD, postpartum depression and post-stroke depression. In the proposed study, a combination of DCEAS and body acupuncture will be employed to prevent and treat chemobrain in breast cancer patients.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Comprehensive acupuncture (CAI) | Active comparator | Procedure: Dense cranial electroacupuncture stimulation, Procedure: Body acupuncture, Drug: Cytoxan-containing chemotherapy regimensBreast cancer patients receiving Cytoxan-containing chemotherapy regimens (Chemo) will receive Dense cranial electroacupuncture stimulation (DCEAS) and Body acupuncture (BA). |
| Least acupuncture stimulation (LAS) | Sham comparator | Procedure: Least acupuncture stimulation, Drug: Cytoxan-containing chemotherapy regimensBreast cancer patients receiving Cytoxan-containing chemotherapy regimens (Chemo) will receive Least acupuncture stimulation (LAS) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Chinese females aged 18 to 65 years;
- have a diagnosis of stage I-IIIa breast cancer; and
- are ready for orally administered or vein injection or both with Cytoxan-containing regimens as adjuvant chemotherapy before or after surgical treatment or in combination with other pharmacotherapy.
Key exclusion criteria (5 listed)
- had chemotherapy in the last 2 years;
- have cardiac pacemakers, epilepsy or other unstable medical conditions;
- had investigational drug treatment within the past 6 months;
- alcoholism or drug abuse within the past 1 year; or
- have severe needle phobia.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dense cranial electroacupuncture stimulationAlso: DCEASDCEAS is a is a novel stimulation mode in which electrical stimulation is delivered on acupoints located on the forehead. Six pairs of acupoints are used: Baihui (GV20) and Yintang (EX-HN3), left Sishencong (EX-HN1) and Toulinqi (GB15), right Sishencong (EX-HN1) and Toulinqi (GB15), bilateral Shuaigu (GB8), bilateral Taiyang (EX-HN5), and bilateral Touwei (ST8). Disposable acupuncture needles (Hwato®, 0.30 mm in diameter and 25-40 mm in length) are inserted at a depth of 10-30 mm perpendicularly or obliquely into acupoints. Manual manipulation is then conducted to evoke needling sensation, followed by electrical stimulation (ITO ES-160, continuous waves at 2 Hz). | Procedure or surgery | Comprehensive acupuncture (CAI) |
| Body acupunctureAlso: BAFollowing acupoints are used: Shui-Gou (GV26), Shen-Men (HT7). He-Gu (LI4), Wai-Guan (TE5), Zhong-Wan (CV12), Guan-Yuan (CV4), Zu-San-Li (ST36), Feng-Long (ST40) and San-Yin-Jiao (SP6). Disposable acupuncture needles (Hwato®, 0.30 mm in diameter and 25-40 mm in length) are inserted at a depth of 10-30 mm perpendicularly or obliquely into acupoints. Manual manipulation is then conducted to evoke needling sensation. No electrical stimulation is delivered. | Procedure or surgery | Comprehensive acupuncture (CAI) |
| Least acupuncture stimulationAlso: LASThe acupoints chosen are less related to the treated syndromes based on Traditional Chinese Medicine (TCM) theory; the number of acupoints used and the intensity of electrical stimulation are also lower than the comprehensive acupuncture regimen. The following 6 acupoints will be used in LAS control: bilateral Tong-Tian (GB17), bilateral Shou San-Li (LI10) and bilateral Fu-Yang (BL59). Electrical stimulation will be only performed on bilateral Tong-Tian (GB17) and the intensities are adjusted to a level at which patients just start feeling the stimulation. | Procedure or surgery | Least acupuncture stimulation (LAS) |
| Cytoxan-containing chemotherapy regimensAlso: ChemoEach subject shall receive oral administration or venous injection or both with adjuvant or neoadujuvant chemotherapy regimens, as decided by clinical oncologist. In clinical practice, the most commonly used Cytoxan-containing regimens include but are not limit to: AC (x4) [Adriamycin + Cytoxan], TC (x4) [Taxotere + Cytoxan], AC-P (4+4) [Adriamycin + Cytoxan + Paclitaxel], TAC (x6) [Taxotere + Adriamycin + Cytoxan], or AC-PH (4+4) [Adriamycin + Cytoxan + Paclitaxel + Herceptin]. | Drug | Comprehensive acupuncture (CAI), Least acupuncture stimulation (LAS) |
Primary outcome
Changes in cognitive function (objective measurement)
Time frame: Baseline, 2 week, 4 week, 6 week, 8 week
The Montreal Cognitive Assessment (MoCA) of corresponding dialects will be used as an objective measurement for subjects' cognitive function. Assessments will be conducted at baseline and every 2 weeks thereafter.
Changes in cognitive function (subjective measurement)
Time frame: Baseline, 2 week, 4 week, 6 week, 8 week
The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) of corresponding dialects will be used as a subjective measurement for subjects' cognitive function. Assessments will be conducted at baseline and every 2 weeks thereafter.
4 secondary outcomes
Changes in quality of Life - composite measure
Time frame: Baseline, 4 week, 8 week
Changes in illness related fatigue measured by FACIT-Fatigue
Time frame: Baseline, 4 week, 8 week
Changes in chemo adverse effects - composite measure
Time frame: Baseline, 4 week, 8 week
Changes in subject perception of chemotherapy treatment measured by FACIT-TS-G
Time frame: Baseline, 4 week, 8 week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2019.
- Background: PubMed 17969831Nelson CJ, Nandy N, Roth AJ. Chemotherapy and cognitive deficits: mechanisms, findings, and potential interventions. Palliat Support Care. 2007 Sep;5(3):273-80. doi: 10.1017/s1478951507000442.
- Background: PubMed 21765260Asher A. Cognitive dysfunction among cancer survivors. Am J Phys Med Rehabil. 2011 May;90(5 Suppl 1):S16-26. doi: 10.1097/PHM.0b013e31820be463.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhang-Jin ZHANG, MMed, PhD principal investigator
The University of Hong Kong
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dense cranial electroacupuncture stimulation, Body acupuncture and Least acupuncture stimulation in people with Chemo-brain and Drug-Related Side Effects and Adverse Reactions, run by The University of Hong Kong at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Hong Kong, China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in cognitive function (objective measurement) (time frame: Baseline, 2 week, 4 week, 6 week, 8 week). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02457039, which also lists 40 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2019.