Effect of Laser Auriculotherapy on Managing Neuropsychological Symptom Clusters in Patients With Gastrointestinal Neoplasms: Protocol for a Randomized Clinical Trial

Abstract

Background

Individuals with gastrointestinal neoplasms undergoing chemotherapy may develop symptoms related to anxiety, fatigue, and sleep disturbances, which are components of neuropsychological symptom clusters. Among non-pharmacological strategies that may aid in symptom management, laser auriculotherapy—a modality of acupuncture—has emerged as a promising approach in symptom management studies.

Objective

This study aims to present a research protocol designed to evaluate the effect of laser auriculotherapy in reducing neuropsychological symptom clusters associated with anxiety, fatigue, and sleep disturbances in patients with gastrointestinal neoplasms undergoing chemotherapy.

Methods

A randomized, controlled, double-blind clinical trial will be conducted, involving 62 patients recruited with gastrointestinal cancer initiating chemotherapy treatment at a University Hospital that is a reference in the treatment of cancer patients. Participants will be randomly assigned to one of two groups: (1) Experimental Group: laser auriculotherapy applied to predetermined and validated acupuncture points, or (2) Control Group: Sham laser auriculotherapy (placebo). Patients will be followed for 4 weeks. Two important moments will be considered to evaluate the results of the intervention (Pre-intervention and Post-intervention). The primary outcomes will include the reduction in anxiety scores measured by the BAI, the reduction in fatigue scores measured by the Piper Fatigue Scale, and the reduction in sleep scores measured by the Pittsburgh Sleep Quality Index. The secondary outcome will evaluate changes in vital parameters ((blood pressure, heart rate, respiratory rate, temperature and oxygen saturation).

Discussion

The study aims to contribute to the reduction of the cluster of neuropsychological symptoms in patients with gastrointestinal cancer, using a non-pharmacological strategy that can be inserted into the clinical practice of health professionals and oncology reference centers.

Keywords

gastrointestinal neoplasm auriculotherapy concurrent symptoms complementary therapies

Introduction

Gastrointestinal system neoplasms involve various organs, including the esophagus, stomach, small intestine, gallbladder, liver, pancreas, colon, and rectum. Among these, the colon and rectum are the most frequently affected sites, followed by stomach and esophageal cancers. These neoplasms contribute significantly to cancer-related morbidity and mortality.^1,2 They are responsible for one in four cancer cases and one in three cancer deaths, with an incidence of 4.8 million cancer cases and 3.4 million cancer-related deaths worldwide.³

Regarding treatment, surgery, chemotherapy, and radiotherapy are commonly employed for gastrointestinal cancer management. Among these modalities, chemotherapy stands out as the treatment that induces the most feared side effects due to its systemic action.⁴

At the onset of diagnosis and chemotherapy treatment, patients with gastrointestinal cancer often experience multiple symptoms influenced by physiological, psychological, and situational factors. Additionally, the carcinogenesis process itself contributes to the emergence of distressing symptoms such as fatigue, cancer-related pain, sleep disturbances, anxiety, and depression, all of which can negatively impact patients’ quality of life.⁵

Among the symptom clusters identified in studies involving oncology patients, neuropsychological clusters are particularly prominent. These are characterized by the presence of emotional and/or behavioral symptoms in patients diagnosed with cancer.⁶ At the beginning of chemotherapy, patients with gastrointestinal cancer often present symptoms such as anxiety, sleep disturbances, and fatigue, which are components of the neuropsychological symptom cluster.⁵

It is noteworthy that patients with gastrointestinal cancer often have fragile mental health due to the long treatment journey and the high recurrence and mortality of the disease.⁷ Managing symptoms associated with cancer diagnosis and chemotherapy initiation poses a challenge for healthcare professionals, necessitating the implementation of strategies to alleviate these symptoms. One such strategy is auriculotherapy—a modality of acupuncture—which operates through mechanisms involving pluripotent cells located in the ear that contain information about the entire body, as well as their connection to energy meridians and organs. Stimulation of acupuncture points can be performed using needles, crystals, seeds, or low-intensity lasers.⁸

Laser auriculotherapy is painless and suitable for individuals with needle phobias. Additionally, laser application can target acupuncture points that are otherwise challenging for needle insertion. Treatment with laser auriculotherapy involves short durations, ranging from 10 to 60 seconds per acupuncture point, which is considerably shorter than the 10 to 30 minutes required for metallic needle retention.⁹

In this context, it is important to recognize groups of symptoms in oncology, and the development of non-pharmacological strategies for holistic care is essential. Studies developed by health professionals addressing symptom management in cancer patients stand out.^10,11

Research on auriculotherapy has demonstrated its benefits in managing conditions such as lower back pain, tendinopathy, osteoarthritis, and emotional symptoms.^12,13 Furthermore, a review carried out with 669 cancer patients pointed to the beneficial effect of auriculotherapy in the management of associated symptoms, such as fatigue, sleep disorders and anxiety. However, among the materials used, the following stand out: needles, seeds, magnetic pellets and crystal balls, demonstrating a need for studies with the laser.¹⁴ A randomized clinical trial evaluating the effects of laser auriculotherapy on women with breast cancer found a reduction in health-related quality of life and cancer-related fatigue in the experimental group. However, further investigation is recommended in different population groups, with different comorbidities and cancer stages.^15,16

Rigorous placebo-controlled clinical trials with detailed intervention protocols are necessary to substantiate its benefits, particularly for managing symptoms in patients with gastrointestinal cancer undergoing chemotherapy. Therefore, this study aims to present a protocol for a randomized clinical trial to evaluate the effect of laser auriculotherapy in reducing neuropsychological symptom clusters, including anxiety, fatigue, and sleep disturbances, in patients with gastrointestinal neoplasms undergoing chemotherapy.

Methods

Study Design

This is a randomized, two-arm, 1:1, placebo-controlled clinical trial with a double-blind design. It aims to evaluate the effect of Laser Auriculotherapy (LA) in reducing neuropsychological symptom clusters, including anxiety, fatigue, and sleep disturbances, in patients with gastrointestinal neoplasms undergoing chemotherapy. The results will be compared to a Control Group consisting of patients receiving Simulated Auriculotherapy (SA) as a placebo.

Participants will be randomly assigned to one of the two intervention groups. The study will adhere to the CONSORT¹⁷ and SPIRIT¹⁸ guidelines (Standard Protocol Items: Recommendations for Interventional Trials). The study considered aspects of the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA).¹⁹

Population and Sample

The study will include patients diagnosed with gastrointestinal cancer who are starting chemotherapy treatment. Sample size was calculated using the G*Power software, version 3.1.9.2 (available at: https://www.gpower.hhu.de/). Assuming a Cohen’s effect size of 0.80, a power of 0.80, and a significance level of 5%, the required sample size is 52. The dropout rate considered will be 20%, which corresponds to a sample of 62 participants for recruitment. The calculation of the sample estimate considered the test power of 80% to guarantee the necessary statistics.^20,21

Eligibility and Recruitment Criteria

Inclusion Criteria

-Patients aged 18 years of older, diagnosed with gastrointestinal cancer, and scheduled to begin chemotherapy treatment.

-Have a Karnofsky Performance Status score greater than 60.

Exclusion Criteria

-Patients with conditions that impair their ability to comprehend or participate in the study;

-Patients already using the complementary therapy employed in this study;

-Patients with active infections or injuries in the auricular pavilion;

-Patients refusal to receive auricular laser treatment;

-Patients with recurrent disease or terminals.

Recruitment

Recruitment will occur in the oncology department of a university hospital. This hospital is a non-profit institution with a High-Complexity Onco-Hematology Care Unit and serves as a referral center for cancer patients. Participants will be recruited upon admission for chemotherapy treatment. They will be contacted and screened based on the eligibility criteria for study participation.

Participant recruitment began on January 20, 2025 and is scheduled to end in January 2026. The clinical trial is in the participant recruitment phase.

Allocation

Participant randomization will be conducted using the website www.randomizer.org, which will assign participants to each group (Control Group - CG or Experimental Group - EG) through simple randomization without researcher influence. The website will generate a list with the sequence of participants evenly divided between the two intervention groups. Randomization will not only avoid selection bias but also ensure comparability of groups regarding known and unknown risk factors. The researcher responsible for administering the data collection instruments, the statistician, and the study participants will be blinded to the group allocation. Participants will wear protective eyewear during laser auriculotherapy to conceal their group assignment.

Initial Assessment

Recruited participants who agree to participate in the study will sign a free and informed consent form. After this, they will be introduced to the study, its interventions, and the instruments used for data collection. Any doubts about the study will be clarified before proceeding with the intervention.

Following this step, participants will be assigned to either the CG or EG based on the pre-generated randomization list. Assessments will be conducted at three time points: T0 (Baseline): Before the intervention, T1 (During the intervention), and F1 (Follow-up): Post-intervention. Table 1 presents the detailed study phases, including the SPIRIT timeline for enrollment, interventions, and assessments.

Table 1.

Shows the Detailed Stages of the Study, Including the SPIRIT Enrollment Schedule, Interventions, and Assessments

Study Period
	Enrolment	Baseline	Post-allocation: Allocation, interventions, follow-up
Timepoint			Allocation	T0	T1 intervention	Follow-up (F1)
Enrolment
Eligibility criteria	X
Recruitment	X
Initial assessment	X
Informed consent	X
Allocation			X
Interventions
Simulated auriculotherapy (control group)					X
Laser auriculotherapy (intervention group)					X
Assessments
Sociodemographic data		X
PSQI-BR				X		X
BAI				X		X
Piper fatigue scale				X		X

Note: T0: Pre-intervention - before the intervention is carried out - the patient’s admission period for chemotherapy; T1: Intervention Period. F1: Post-intervention: After the intervention is completed, the questionnaires will be administered again.

Study Groups

The experimental group will be composed of patients diagnosed with gastrointestinal cancer undergoing chemotherapy. These patients will receive laser auriculotherapy applied to predetermined auricular points to reduce anxiety, fatigue, and sleep disorders.

The control group will be composed of patients diagnosed with gastrointestinal cancer undergoing chemotherapy who will receive simulated laser auriculotherapy as a placebo. The laser device will remain off, and no activation of auricular points will occur.

Intervention

Patients selected for the study will be invited to participate and provided with an explanation of the research stages, objectives, risks, and benefits. The Free and Informed Consent Form (ICF) will be presented and signed during their first nursing consultation for chemotherapy.

After consenting, the following instruments will be applied by a trained researcher (P1): Sociodemographic and Clinical Characteristics Form, Pittsburgh Sleep Quality Index (PSQI-BR), Piper Fatigue Scale, and the Beck Anxiety Inventory (BAI). The instruments will be administered to all participants (EG and CG) before the intervention. Importantly, the study adheres to blinding protocols, ensuring the researcher (P1) is unaware of group allocations.

The principal researcher will measure physiological parameters with the participant seated after five minutes of rest. The same device will be used for all participants, and it will be disinfected with 70% alcohol after each use.

For the EG, participants will be seated in a chair, and their auricular pavilion will be cleaned with cotton soaked in 70% alcohol. Protective glasses will be provided due to the laser light. Laser auriculotherapy will then be applied to the following points: Shenmen, kidney, spleen, sympathetic, liver, heart, and anxiety. These auricular points were selected based on a literature review and validated by expert judges.¹⁴ Figure 1 provides a visualization of the selected points. Chart 1 and Chart 2 details the application of the points in the intervention, indication and location.

Figure 1.

Application Points for Reducing Anxiety-Fatigue and Sleep Disorders. *Note: SN: Nervous System; TCM: Traditional Chinese Medicine

Chart 1.

Laser Auriculotherapy Application Protocol

Application protocol
Application points	Device	Number of sessions	Laser frequency
Shenmen, kidney, sympathetic, heart, anxiety, liver, and spleen	Low-power laser – DMC equipment – wavelength: 660 nm (red laser)	Once a week for four weeks	2 joules per acupoint, applied for 20 seconds at each point

Chart 2.

Description of the Indication and the Location of the Auricular Points

Points	Indication	Location
Shenmen	Emotional stability and reduction of anxiety	In the triangular fossa, at the apex of the angle formed by the upper and lower branches of the antihelix
Kidney	Hormonal balance/energy function, improvement of fatigue, anxiety and stress	In the cymba concha, close to the junction of the lower branch of the antihelix, on the same vertical line as the Shen Men point
Sympathetic	Self-regulation of the body’s biological systems	At the intersection of the lower branch of the antihelix and the inner face of the helix
Anxiety	Anxiety, agitation, insomnia, emotional stress and irritability	In the lower portion of the earlobe, proximal to the face
Heart	Anxiety and insomnia	Is located in the center of the depression of the cavum conchae
Liver	Control of emotions, depression, irritability and stress, contributes to states of fatigue	In the cymba concha, proximal to the junction with the antihelix, just above the beginning of the root of the helix
Spleen	Contributes to states of fatigue, worries and balance	In the upper and posterior portion of the concha cava

The choice of Shenmen, Kidney and Autonomic Nervous System (NVS) points are characterized as “opening points”, due to their role in opening or unclogging energy channels in auriculotherapy and in promoting the adequate flow of vital energy in the body, contributing to relaxation. Anxiety and heart points help with emotional symptoms related to anxiety, relaxation, and sleep disorders. The spleen and liver points contribute to regulating bodily function and reducing oncological fatigue.^14,16

Participants in the EG will undergo one session of laser auriculotherapy per week for 4 weeks, coinciding with their chemotherapy sessions. For the CG, the same process will be followed, but the laser device will remain off.

The number of sessions was chosen based on a review of the literature that presented studies with auriculotherapy protocols lasting four weeks or more with symptom reduction.^14,15,22,23

The ear mapping followed the location references of the Auriculotherapy Atlas²⁴ and the World Federation of Acupuncture-Moxibustion Societies.²⁵ The treatment will be unilateral with alternating ear auricle, starting with the participant’s dominant side.

In the CG, participants will receive simulated auriculotherapy as a placebo. They will be seated in a chair and provided with protective goggles as part of the blinding process. A laser device will be used but kept off, with no laser emission, ensuring that the auricular points are not stimulated. The auricular pavilion will be cleaned using cotton soaked in 70% ethanol.

After the intervention, physiological parameters will again be measured for both groups. Each participant will remain seated for five minutes while the principal investigator records their vital signs.

It is important to note that the auriculotherapy sessions will take place in the chemotherapy outpatient clinic, with scheduling arranged beforehand in coordination with the institution’s management. The sessions will be conducted by a researcher trained in auriculotherapy.

Data collection instruments will be applied at two points: before the intervention begins and during the final session. The protocol for application points, technique, materials, and number of laser auriculotherapy sessions was developed by the researchers and validated by a panel of expert judges.

Data Collection Instruments

The following instruments will be used for data collection.

Socio Demographic and Clinical Characteristics Form

An adapted form from the study by Nunes and Ceolim (2019),⁴ which was developed and validated by researchers with experience in oncology and in validating instruments for collecting sociodemographic data from cancer patients.

Pittsburgh Sleep Quality Index (PSQI-BR)

Validated for the Brazilian culture, this instrument is divided into seven components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medications, and daytime dysfunction. The components are scored from zero to three, and the total score ranges from zero to 21 points. A score higher than five indicates poor sleep quality, while scores equal to or lower than five indicate good sleep quality.^26,27

Beck Anxiety Inventory (BAI)

The instrument was adapted to Portuguese to assess common symptoms of anxiety. It consists of 21 questions, each with four possible responses corresponding to the level of anxiety. The classification based on the score is as follows: 0-10: minimal, 11-19: mild, 20-30: moderate, and 31-63: severe.²⁸

Piper Fatigue Scale

This scale was revised and validated for the Brazilian oncology population. It is a multidimensional assessment tool containing 22 items and five open-ended questions, which are not used in the score calculation but provide additional data on fatigue. The scale covers three dimensions: behavioral (items 2 to 7), affective (items 8 to 12), and sensory/psychological (items 13 to 23).²⁹

Additionally, physiological parameters such as heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature (T), and oxygen saturation (SpO2) will be measured before and after each intervention by a single evaluator during all sessions.

A field diary will also be used for the researcher to record important notes, such as participant exclusions and losses to follow-up. It is emphasized that participant losses and dropouts will be carefully documented to ensure the reliability of the study.

Expected Results - Primary Outcomes

The primary outcomes will include the reduction in anxiety scores measured by the BAI, the reduction in fatigue scores measured by the Piper Fatigue Scale, and the reduction in sleep scores measured by the Pittsburgh Sleep Quality Index.

Secondary Outcomes

Secondary outcomes will include the evaluation of physiological parameters during the sessions of laser auriculotherapy. This will involve identifying whether the use of laser auriculotherapy leads to changes in vital signs (heart rate, respiratory rate, blood pressure, temperature, and oxygen saturation).

Safety Outcomes

Safety outcomes include the assessment of adverse events during the study, respecting ethical principles related to research involving human subjects. Adverse events will be recorded and assessed during the intervention sessions.

Adverse events will be assessed by asking participants about self-reported adverse events.

Management of Losses and Dropouts

Losses and dropouts will be carefully recorded to ensure the reliability of the study. If a participant from the sample decides to withdraw from the study, they will be removed from data collection, and another participant will be included.

Study Discontinuation Criteria

Regarding the discontinuity criteria, the following stand out.

-Patients who refuse to continue participating in the intervention;

-Give up conventional treatment or interrupt treatment;

-Do not attend consecutive sessions for personal reasons or complications;

-Death.

Blinding

The study will be double-blind, meaning that both participants and those performing statistical analysis of the research data will be unaware of the group assignments (intervention group with laser auriculotherapy and control group with simulated laser auriculotherapy). Furthermore, data collection instruments will be applied by a researcher who does not know the group to which each participant belongs. However, the researcher performing the intervention will not be blinded, which means the field team will not be fully blinded.

Allocation Concealment

The researcher responsible for administering the data collection instruments, the statistician, and the study participants will be blinded to group allocation. Participants will wear protective eyewear during laser auriculotherapy to conceal their group assignments.

Data Collection and Management

The study will be coordinated by a researcher with over 10 years of research experience. An assistant researcher will be responsible for recruiting participants and applying the intervention in both the control and intervention groups. A second researcher will administer the post-intervention questionnaires without knowledge of the group assignments. The entire process of data collection and analysis will be supervised by the principal investigator.

The researchers will ensure that participants’ anonymity is protected, and all personal data will remain confidential, safeguarding their identities and any identifying information. Prior to the intervention, training will be provided regarding the questionnaires and the application of auricular points.

Data Analysis

The data collected in this study will be stored and processed in a computerized database using Microsoft Office Excel 2010 and Statistical Package for the Social Sciences (SPSS) version 20.0.

Descriptive and inferential statistics will be performed on the collected variables, and the results will be presented in tables, charts, and figures. To assess the relationship between variables, the Chi-square test (χ²), Fisher’s test, or Student's t-test will be used. Additional statistical tests will be employed as needed. A significance level of 5% (P = 0.05) will be adopted for the entire study, with other statistical tests used as necessary. Heterogeneity analysis will be performed between groups and subgroup analysis will also be performed.

Ethical Considerations

The present study was analyzed and approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte – UFRN – CAAE - 81496224.9.0000.5537 (August 8, 2024). This study was also registered in the Brazilian Registry of Clinical Trials – REBEC - RBR-9pvbx34 as a clinical trial (November 12, 2024).

Participant involvement will be voluntary, non-profit, and will occur after reading and signing the Informed Consent Form (ICF), which indicates that the individual agrees to participate in the study, outlining all stages, objectives, risks, and benefits. Participants may withdraw at any stage of the study without affecting their treatment and without penalty or judgment of any kind. Consent will be obtained in writing from each research participant. The flow diagram of the study is displayed in Figure 2 below.

Figure 2.

Flow Diagram of Study Follow-Up Adapted From CONSORT 2010

Discussion

The experience of symptoms in cancer patients has contributed to new advancements in science, driving research on symptom clusters to better understand the patterns of association, interaction, and synergy among multiple symptoms.³⁰

An important fact is that the cluster of neuropsychological symptoms is related to biobehavioral changes. These changes were first described through the phenomenon of “sickness behavior,” where altered behavior in rodents was observed following infection induction and the injection of pro-inflammatory cytokines in the laboratory.^6,10

Similarly to sickness behavior, an elevation in pro-inflammatory cytokines has been observed in cancer patients, linked to biobehavioral changes such as fatigue, mood disorders, cancer-related pain, cognitive disturbances, and sleep disorders.¹⁰

It is noteworthy that the release of cytokines such as IL-1β, IL-6, IL-8, TNF-α, IL-12p70, and IFN-γ is associated with neuropsychological symptoms, including depressed mood, fatigue, depression, sleep disturbances, and pain.^6,31

In patients with gastrointestinal neoplasms undergoing chemotherapy, the presence of symptoms such as fatigue, anxiety, and sleep disturbances is common, necessitating the planning of healthcare professionals’ actions to help improve these symptoms.⁵

In this context, Complementary and Alternative Medicine (CAM) has increasingly gained attention for cancer patients, contributing to the management of symptoms related to both neoplasms and oncological treatments.³²

Among CAM practices is auriculotherapy, a modality of acupuncture that is based on the concept that the auricular pavilion is a microsystem, and through stimulation of localized points on the ear, symptom relief can be promoted for conditions such as pain,¹⁰ anxiety, stress, and sleep disorders.^14,33

It is worth noting that with the advancement of technology, various methods for stimulating the points have emerged, with low-intensity laser auriculotherapy being prominent. The use of laser light has been highlighted for nearly three decades through low-intensity lasers, which induce a photochemical reaction in cells known as photobiomodulation.^34,35

The use of auriculotherapy in the management of neuropsychological symptom clusters, with a focus on anxiety, fatigue, and sleep disturbances in patients with gastrointestinal cancer, is still incipient in the literature. However, studies have utilized low-intensity lasers for pain and emotional symptoms in populations with breast cancer or undergoing palliative chemotherapy.^12,13

One study that tested an auriculotherapy protocol for pain, fatigue, and sleep disorder management in women with breast cancer demonstrated symptom reduction and highlighted auriculotherapy as a complementary practice for managing symptoms in women with breast cancer.³⁶

The mechanism of action of auriculotherapy, particularly in emotional disturbances such as anxiety, may be linked to its effects on the nervous system, promoting the release of endorphins and melatonin in the brain, which contributes to relaxation and the balance of the autonomic nervous system.³⁷

Overall, non-pharmacological strategies for symptom management, are being tested and have provided patients with greater self-control over their symptoms.^38-41 It is noteworthy that this study meets the sustainable development objective related to health and well-being of the World Health Organization, especially with regard to promoting the management of oncological symptoms.⁴²

Conclusion

This clinical trial protocol aims to contribute to the management of neuropsychological symptoms in patients with gastrointestinal cancer, using a non-pharmacological strategy that can be inserted into the clinical practice of health professionals and oncology reference centers.

Footnotes

ORCID iDs

Silmara de Oliveira Silva

Rodrigo Assis Neves Dantas

Daniele Vieira Dantas

Ethical Considerations

The present study was analyzed and approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte – UFRN – CAAE - 81496224.9.0000.5537 (August 8, 2024).

Consent to Participate

Authors Contributions

Principal responsibility for the study design and conduct was assumed by SOS, MES, DVD and RAND. All authors contributed to study design. JFF, VDLP, RPPOAC, and MCBS drafted the manuscript. All authors read and commented on drafts and approved the final manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Clinical Trial Registration

RBR-9pvbx34 - Brazilian Registry of Clinical Trials - REBEC - ().

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