A Pilot Study of Acupuncture Treatment for Dysphagia

Study Overview
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Brief Summary
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The current standard of care for advanced HNC is concurrent chemoradiation therapy (CRT), which has led to increased survival rates, but with significant acute and long-term toxicities. Dysphagia, or difficulty with swallowing, is a common and expected side effect during and following CRT. Dysphagia occurs in up to 50% of patients and significantly impairs the quality of life (QOL) of patients during delivery of and recovery from CRT. Clinical trials evaluating promising and innovative adjunctive approaches that could increase the rate and magnitude of recovery from dysphagia in HNC patients are needed. Acupuncture is a traditional Chinese medical technique that has been found to reduce symptoms and side effects associated with primary cancer therapy. This study evaluated the feasibility of conducting a randomized sham-controlled trial and collected preliminary data on safety and efficacy of acupuncture.

Detailed Description
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AIMS: Aim 1. To assess the feasibility of recruiting and retaining HNC patients with dysphagia into a randomized sham-controlled trial of acupuncture. Aim 2. To collect preliminary data on the efficacy of acupuncture in changing scores of HRQOL in post CRT head and neck cancer patients. Aim 3. (Exploratory) In a subset of HNC subjects treated with both active and sham acupuncture, to collect objective measures on swallowing functions using Videofluoroscopic swallowing study (VFSS); salivary flow production; and plasma Transforming Growth Factor (TGF)-β1, Interleukin 6 (IL-6), Tumor necrosis factor-alpha (TNF-α) and Interleukin 13 levels.

Official Title
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Acupuncture for Dysphagia After Chemoradiation Therapy in Head and Neck Cancer Patients: A Pilot Randomized Control Trial

Conditions
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Carcinomas, Squamous Cell, Dysphagia

Intervention / Treatment
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* Device: Acupuncture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically proven squamous cell carcinoma of the head and neck (SCCHN) at stage II, III and IV, without evidence of distant metastasis. Stage I disease will also be permitted if the patient is receiving CRT; Primary tumor sites eligible: nasopharyngeal, oropharynx, hypopharynx or larynx. Tumors of the nasal and paranasal cavities will also be included. Unknown primary squamous cell carcinoma (SCC) in the neck will also be eligible. SCC of the oral cavity will also be eligible with the approval of the treating staff; Receiving chemoradiation; Currently or recently undergoing swallowing therapy program with or without feeding tube use, with or without neck dissection; Age ≥ 18 years; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Adequate hematological function: neutrophil count >1.0 x109/L, platelet count >50x109/L Signed informed consent. Exclusion Criteria Patients with the following criteria will NOT be eligible for the study: Unstable cardiac disease or myocardial infarction within 6 months prior to study entry; Wearing a pacemaker or implantable cardioverter-defibrillator; History of significant neurologic disorder that affects swallowing, including stroke, neurodegenerative disease, advanced dementia, or uncontrolled seizure disorder; Active clinically significant uncontrolled infection; Prior use of acupuncture for dysphagia;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Acupuncture<br>The active intervention used a three-phase step-up protocol to gradually increase the body areas treated and needling intensity. Acupuncture needles (0.20x25mm) were inserted with a depth of 5-10 mm into predefined points based on a systematic literature review following the STRICTA guideline. Needles were stimulated to obtain the de qi sensation. An electroacupuncture (EA) device was connected at two acupoints. All needles remained in place for 30 minutes. The active acupuncture was administered once every 2 weeks for 24 weeks, starting 2 weeks into CRT and ending at 20 weeks after CRT. [Refs: Lu W, Wayne PM et al. Contemp Clin Trials 2012; 33; 700-711; MacPherson H, Altman DG et al. PLoS Med 2010;7:e1000261] | Device: Acupuncture<br> <br> |
| Sham Comparator: Sham Acupuncture<br>The sham intervention was designed to be maximally inert and minimally invasive, while simulating most aspects of the active protocol. Sham needles (0.12x30mm) were inserted at 14 locations paralleling the same body regions needled in the active group; however, all sham point locations were off the pathways of traditional Chinese medicine acupuncture meridians and points. An identical but deactivated EA device was used following sham protocols previously used. The sham acupuncture was administered once every 2 weeks for 24 weeks, starting 2 weeks into CRT and ending at 20 weeks after CRT. [Refs: Lu W, Wayne PM et al. Contemp Clin Trials 2012; 33; 700-711; Wayne PA, Krebs DE et al. Arch Phys Med Rehabil 2005;86:2248-2255] | Device: Acupuncture<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Outcome Compliance Rate | Outcome compliance rate is the percentage of enrolled participants who completed the primary study assessments (at baseline and in long-term follow-up 6 months post acupuncture treatment). | Assessed at baseline and at 6 months post acupuncture treatment | 
| Treatment Compliance Rate | Treatment compliance rate is the percentage of enrolled participants who completed at least 80% of treatment (10 of 12 acupuncture sessions). | Assessed throughout the 6 month treatment period (12 acupuncture treatments every 2 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MDADI Change From Baseline to 12 Months Post Chemoradiation Therapy (CRT) | The M.D. Anderson Dysphagia Inventory (MDADI) is a validated, self-administered questionnaire established as the best measure of dysphagia-related quality of life in HNC patients. (Carlsson S, et al Dysphagia 2012; 27: 361-369). MDADI has two summary scores: 1) global (1 item) and 2) composite (19 items). Each item is scored on a 5 point Likert scale (strongly disagree, disagree, no opinion, agree, strongly agree). The composite MDADI score is a weighted average of the physical, emotional, and functional subscale questions. Scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning). A minimal clinically important within group difference was a 10% change from baseline. | Assessed at baseline and 6 months post acupuncture which parallels 12 months post-CRT | 
| MDADI Scores | The M.D. Anderson Dysphagia Inventory (MDADI) is a validated, self-administered questionnaire established as the best measure of dysphagia-related quality of life in HNC patients. (Carlsson S, et al Dysphagia 2012; 27: 361-369). MDADI has two summary scores: 1) global (1 item) and 2) composite (19 items). Each item is scored on a 5 point Likert scale (strongly disagree, disagree, no opinion, agree, strongly agree). The composite MDADI score is a weighted average of the physical, emotional, and functional subscale questions. Scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning). A minimal clinically important within group difference was a 10% change from baseline. | Assessed at baseline, 20 weeks post chemoradiation therapy and 6 months post acupuncture | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acupuncture, dysphagia, chemoradiation related effects, squamous cell carcinoma of the head and neck, nasopharyngeal cancer, oropharynx cancer, hypopharynx cancer, larynx cancer