Efficacy of Electrical Stimulation for Dysphagia in Head & Neck Cancer Patients

• Sponsor: Boston Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00629265
• Collaborator: Northwestern University (Other), Boston University (Other), University of Wisconsin, Madison (Other), New York University (Other), VA Boston Healthcare System (U.S. Fed), Lahey Clinic (Other), Lenox Hill Hospital (Other), Beth Israel Medical Center (Other), Greater Baltimore Medical Center (Other), Henry Ford Hospital (Other), University of California, San Diego (Other), University of Washington (Other), Mayo Clinic (Other), Icahn School of Medicine at Mount Sinai (Other), National Cancer Institute (NCI) (NIH)
• Enrollment: 170
• Locations: 14
• Arms: 2
• Duration (Months): 62
• Patients Per Site: 12.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of the investigation is to learn whether intense swallowing exercise or intense swallowing exercise coupled with electrical stimulation (E-Stim) helps patients who had head/neck cancer and currently have dysphagia swallow better.

Condition or Disease	Intervention/Treatment	Phase
Dysphagia	Device: Neurotech NT2000 Neuromuscular Electrical Stimulation (NMES)	N/A

Detailed Description

Head and neck cancer patients have a better chance of survival in the 21st century because of radiation therapy (RT), either alone or in combination with surgery and/or chemotherapy (CRT). Such therapy has a high rate of local / regional control, and may extend duration of life. Unfortunately the elimination of the cancer can leave devastating side effects, including the inability to eat and swallow normally. Organ preservation, often assumed to be the preferred treatment, has now been shown to magnify dysphagia. Incidence of dysphagia in this group of patients is extremely high, with symptoms continuing to deteriorate for several years after treatment. Conventional therapy for dysphagia yields only minor benefit. Persistence of dysphagia has a major impact on the quality of life of these cancer survivors.

Recently, a new therapy approach has been introduced for dysphagia, called e-stim or Neuromuscular Electrical Stimulation (NMES). Through low voltage current delivered through the skin, motor nerves are excited, causing muscle contraction. An aggressive marketing campaign has turned e-stim into a very popular and sought-after therapy for dysphagia. However, there are no efficacy studies demonstrating its true benefit.

We have collected preliminary data with Head & Neck cancer patients using this modality and have seen improved swallow function in 9/15 patients. This is extremely promising and supports the need for a randomized clinical trial. The randomized controlled trial (RCT) proposed here will compare NMES therapy combined with exercise therapy to a sham NMES protocol combined with the same exercise therapy.

These therapies will be given to post-radiated H&N cancer patients who have moderate to severe dysphagia at least 3 months post-XRT (or post-XRT + post-CRT), to determine whether NMES is efficacious. Therapy will continue for 12 weeks with an intense, daily home program. Objective indicators of a change in swallow function will be taken from modified barium swallow (MBS) studies. Subjective measures of change will be the patients' self-reported diet, eating ability, and quality of life, and will indicate whether they perceived a benefit from the therapy.

This new treatment may represent the first real hope for improved swallowing in this growing population of cancer survivors. We need to determine whether it represents a truly beneficial treatment or whether our resources should be redirected. If successful, this study will stimulate a multitude of additional research to elucidate the mechanisms underlying this new treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 170 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy of Electrical Stimulation for Dysphagia in Head & Neck Cancer Patients
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active NMES + Swallowing Exercise Active Neurotech NT2000 Neuromuscular Electrical Stimulation (NMES) therapy will be paired concomitantly with repeated effortful sallowing exercises, for 60 swallows, 2 times per day, 6 days per week, for 12 weeks.	Device: Neurotech NT2000 Neuromuscular Electrical Stimulation (NMES); NMES or Sham NMES will be paired with repeated, effortful swallowing behavior, for 60 swallows, 2 times a day, 6 days a week, for 12 weeks.; Other Names: E-Stim Neurotech NT2000
Sham Comparator: Sham NMES + Swallowing Exercise Sham (inactive) Neurotech NT2000 Neuromuscular Electrical Stimulation (NMES) therapy will be paired concomitantly with repeated effortful sallowing exercises, for 60 swallows, 2 times per day, 6 days per week, for 12 weeks.	Device: Neurotech NT2000 Neuromuscular Electrical Stimulation (NMES); NMES or Sham NMES will be paired with repeated, effortful swallowing behavior, for 60 swallows, 2 times a day, 6 days a week, for 12 weeks.; Other Names: E-Stim Neurotech NT2000

Outcome Measures

Primary Outcome Measures

1. Change in Penetration-Aspiration Scale (PAS) Score [Before and after treatment]

   The PAS scale is a validated 8-point ordinal scale (Rosenbek et. al 1996) in which a score of 1 is best (material does not enter the airway) and a score of 8 is worst (material enters the airway, passes below the vocal folds, and no effort is made to eject it). Difference in mean PAS scores after 12 weeks of therapy was analyzed between the two groups of interest: Active NMES + Swallowing Exercise versus Sham (inactive) NMES + Swallowing Exercise. PAS scores were obtained from fluoroscopy (modified barium swallow) studies adminstered at three time points - enrollment, midway through treatment (6 weeks), and at end of treatment (12 weeks). All fluoroscopy studies were sent to, and analyzed by, a blinded external central laboratory.

Secondary Outcome Measures

1. Performance Status Scale for Head and Neck Cancer Patients (PSS); The Head and Neck Cancer Inventory (HNCI) [Before and after treatment]

   Perceive improved in quality of life and eating ability as measured by 2 validated scales: the Performance Status Scale for Head and Neck Cancer Patients (PSS) and The Head and Neck Cancer Inventory (HNCI). The PSS (List, et. al., 1990) is a clinician adminsitered scale that has three domains (normalcy of diet, eating in public, and understandability of speech). Each domain as well as overall score is scored on a scale of 0-100, with 0=worst and 100=best. The HNCI (Funk, et. al., 2003) is patient administered questionnaire that has four domains (social disruption, aesthetics, speech, eating). Each domain as well as overall score is scored on a scale of 0-100, with 0=worst and 100=best.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female ages 21+

• At least 3 months post-radiation therapy for head & neck cancer

• Treatment for their cancer can include chemotherapy.

• Surgery for their cancer, if done, must meet these criteria:

• diagnostic biopsy

• less than ½ of oral tongue resected

• less than ½ of tongue base resected

• no floor of mouth muscles resected

• less than 50% of any other part of the oral cavity, pharynx or larynx resected

• no resection of hyoid

• Neck dissection, unilateral or bilateral neck dissections may have been completed prior to or after radiation therapy.

• Currently free of cancer, confirmed by head and neck exam within 2 months of beginning the study

• MBS demonstrates penetration or aspiration on at least one swallow during the study (minimum PAS = 4)

• The patient is free of any medical conditions that could limit the patient's ability to follow the protocol.

• No history of any swallowing problems prior to the onset of head and neck cancer

• Prior swallow therapy, if given to the patient, is neither an Inclusion nor Exclusion criteria

Exclusion Criteria:

• Inability to cooperate with the examination and treatment.

• An implanted electrical device (e.g., pacemaker, deep brain stimulator, defibrillator, vagal nerve stimulator)

• Previous e-stim treatment to the head & neck

• Any current or previous neurological disease which may adversely affect swallowing.

• History of oropharyngeal swallowing disorder prior to cancer.

• History of pre-cancer oral intake that was limited due to a swallowing problem.

• Previous neurosurgery on the brain that could compromise swallowing or ability to follow protocol.

• Severe COPD (oxygen dependent).

• Need for dilation of the upper esophageal sphincter or esophagus at time of entry.

• Females who are currently pregnant will be excluded from participation.

• Females of childbearing potential must have a negative pregnancy test and must be practicing a medically accepted means of contraception (including, but not limited to, condoms, diaphragms/caps, contraceptive pills, contraceptive rings/patches, intrauterine devices, hysterectomy or abstinence)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Scottsdale	Arizona	United States	85259
2	University of California, San Diego	San Diego	California	United States	92103
3	Northwestern University	Evanston	Illinois	United States	60208
4	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
5	Lahey Clinic	Burlington	Massachusetts	United States	01805
6	VA Boston Healthcare	West Roxbury	Massachusetts	United States	02132
7	Henry Ford Hospital	Detroit	Michigan	United States	48202
8	Mayo Clinic	Rochester	Minnesota	United States	55905
9	Beth Israel Medical Center	New York City	New York	United States	10003
10	Lenox Hill Hospital	New York City	New York	United States	10021
11	New York University	New York	New York	United States	10016
12	Mout Sinai Medical Center	New York	New York	United States	10029
13	University of Washington	Seattle	Washington	United States	98195
14	University of Wisconsin	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• Boston Medical Center
• Northwestern University
• Boston University
• University of Wisconsin, Madison
• New York University
• VA Boston Healthcare System
• Lahey Clinic
• Lenox Hill Hospital
• Beth Israel Medical Center
• Greater Baltimore Medical Center
• Henry Ford Hospital
• University of California, San Diego
• University of Washington
• Mayo Clinic
• Icahn School of Medicine at Mount Sinai
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Susan Langmore, PhD,SLP,BRS, Boston University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Susan Langmore, Director, Speech Language Pathology, Boston Medical Center
• ClinicalTrials.gov Identifier: NCT00629265
• Other Study ID Numbers: H-26283; 5R01CA120950
• First Posted: Mar 5, 2008
• Last Update Posted: Oct 31, 2014
• Last Verified: Oct 1, 2014

• Keywords provided by Susan Langmore, Director, Speech Language Pathology, Boston Medical Center: Dysphagia; Neuromuscular Electrical Stimulation (NMES); Head & Neck Cancer; Radiation and ChemoTherapy
• Additional relevant MeSH terms: Head and Neck Neoplasms; Deglutition Disorders

Study Results

Participant Flow

Recruitment Details	170 subjects were recruited/randomized into the study from 16 medical centers in the United States between January 2009 and December 2011. The majority of subjects were recruited during follow up visits in outpatient Otolaryngology & Radiation Oncology clinics.
Pre-assignment Detail	All potentially eligible patients were screened with a 19 question eligibility form. 488 patients were screened, of which 318 were not eligible or declined to participate. 170 patients were then randomized to either the Active NMES + Swallowing Exercise group or the Sham (inactive) NMES + Swallowing Exercise group.

Arm/Group Title	Active NMES + Swallowing Exercise	Sham NMES + Swallowing Exercise
Arm/Group Description	Active NMES paired concomitantly with repeated, effortful swallowing exercises, for 60 swallows, 2 times a day, 6 days a week, for 12 weeks.	Sham (inactive) NMES paired concomitantly with repeated, effortful swallowing exercises, for 60 swallows, 2 times a day, 6 days a week, for 12 weeks.
Period Title: Overall Study
STARTED	116	54
COMPLETED	84	34
NOT COMPLETED	32	20

Baseline Characteristics

Arm/Group Title	Active NMES Group	Sham NMES Group	Total
Arm/Group Description	NMES therapy combined with exercise therapy	Sham NMES combined with exercise therapy	Total of all reporting groups
Overall Participants	116	54	170
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.1 (9.2)	61.5 (10.6)	61.9 (9.6)
Sex: Female, Male (Count of Participants)
Female	16 13.8%	9 16.7%	25 14.7%
Male	100 86.2%	45 83.3%	145 85.3%
Region of Enrollment (participants) [Number]
United States	116 100%	54 100%	170 100%

Outcome Measures

1. Primary Outcome

Title	Change in Penetration-Aspiration Scale (PAS) Score
Description	The PAS scale is a validated 8-point ordinal scale (Rosenbek et. al 1996) in which a score of 1 is best (material does not enter the airway) and a score of 8 is worst (material enters the airway, passes below the vocal folds, and no effort is made to eject it). Difference in mean PAS scores after 12 weeks of therapy was analyzed between the two groups of interest: Active NMES + Swallowing Exercise versus Sham (inactive) NMES + Swallowing Exercise. PAS scores were obtained from fluoroscopy (modified barium swallow) studies adminstered at three time points - enrollment, midway through treatment (6 weeks), and at end of treatment (12 weeks). All fluoroscopy studies were sent to, and analyzed by, a blinded external central laboratory.
Time Frame	Before and after treatment

Outcome Measure Data

Analysis Population Description

Note: the number of participants analyzed (125) does not match the total number enrolled (170) because 45 people did not have adequate follow up data required for this primary analysis.

Arm/Group Title	Active NMES + Swallowing Exercise	Sham (Inactive) NMES + Swallowing Exercise
Arm/Group Description	Active NMES paired concomitantly with repeated, effortful swallowing exercises, for 60 swallows, 2 times a day, 6 days a week, for 12 weeks.	Sham (inactive) NMES paired concomitantly with repeated, effortful swallowing exercises, for 60 swallows, 2 times a day, 6 days a week, for 12 weeks.
Measure Participants	90	35
Mean (Standard Deviation) [Change in points on PAS]	0.01 (1.04)	-0.57 (1.62)

2. Secondary Outcome

Title	Performance Status Scale for Head and Neck Cancer Patients (PSS); The Head and Neck Cancer Inventory (HNCI)
Description	Perceive improved in quality of life and eating ability as measured by 2 validated scales: the Performance Status Scale for Head and Neck Cancer Patients (PSS) and The Head and Neck Cancer Inventory (HNCI). The PSS (List, et. al., 1990) is a clinician adminsitered scale that has three domains (normalcy of diet, eating in public, and understandability of speech). Each domain as well as overall score is scored on a scale of 0-100, with 0=worst and 100=best. The HNCI (Funk, et. al., 2003) is patient administered questionnaire that has four domains (social disruption, aesthetics, speech, eating). Each domain as well as overall score is scored on a scale of 0-100, with 0=worst and 100=best.
Time Frame	Before and after treatment

Outcome Measure Data

Analysis Population Description

Note: the number of participants analyzed (126) does not match the total number enrolled (170) because 44 people did not have adequate follow up data required for this secondary analysis.

Arm/Group Title	Active NMES + Swallowing Exercise	Sham (Inactive) NMES + Swallowing Exercise
Arm/Group Description	Active NMES paired concomitantly with repeated, effortful swallowing exercises, for 60 swallows, 2 times a day, 6 days a week, for 12 weeks.	Sham (inactive) NMES paired concomitantly with repeated, effortful swallowing exercises, for 60 swallows, 2 times a day, 6 days a week, for 12 weeks.
Measure Participants	91	35
Change in Total PSS score	6.25 (14.45)	4.52 (16.06)
Change in HNCI Eating Domain	6.31 (17.92)	6.74 (15.59)

Adverse Events

Time Frame	3 years, 4 months
Arm/Group Title	Active NMES + Swallowing Exercise		Sham (Inactive) NMES + Swallowing Exercise
Arm/Group Description	Active NMES paired concomitantly with repeated, effortful swallowing exercises, for 60 swallows, 2 times a day, 6 days a week, for 12 weeks.		Sham (inactive) NMES paired concomitantly with repeated, effortful swallowing exercises, for 60 swallows, 2 times a day, 6 days a week, for 12 weeks.
All Cause Mortality
	Active NMES + Swallowing Exercise		Sham (Inactive) NMES + Swallowing Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Active NMES + Swallowing Exercise		Sham (Inactive) NMES + Swallowing Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/116 (12.1%)		5/54 (9.3%)
Blood and lymphatic system disorders
Blood pressure complications	1/116 (0.9%)	1	0/54 (0%)	0
Gastrointestinal disorders
Abdominal Pain	0/116 (0%)	0	1/54 (1.9%)	1
PEG Complications	2/116 (1.7%)	2	0/54 (0%)	0
General disorders
Death	2/116 (1.7%)	2	0/54 (0%)	0
Dehydration requiring hospitilization	1/116 (0.9%)	1	0/54 (0%)	0
Immune system disorders
Acute allergic reaction to cat	0/116 (0%)	0	1/54 (1.9%)	1
Musculoskeletal and connective tissue disorders
Excision of Necrotic Mass	1/116 (0.9%)	1	0/54 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Recurrence in Head & Neck	3/116 (2.6%)	3	0/54 (0%)	0
New Cancer / METs (other than Head & Neck)	0/116 (0%)	0	1/54 (1.9%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	2/116 (1.7%)	2	1/54 (1.9%)	1
Airway obstruction	0/116 (0%)	0	1/54 (1.9%)	1
Exacerbation of COPD	1/116 (0.9%)	1	0/54 (0%)	0
Progressive shortness of breath	1/116 (0.9%)	1	0/54 (0%)	0
Surgical and medical procedures
Lung biopsy for suspicious mass	1/116 (0.9%)	1	0/54 (0%)	0
Other (Not Including Serious) Adverse Events
	Active NMES + Swallowing Exercise		Sham (Inactive) NMES + Swallowing Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/116 (10.3%)		7/54 (13%)
Gastrointestinal disorders
Severe Heartburn	0/116 (0%)	0	1/54 (1.9%)	1
Diarrhea	1/116 (0.9%)	1	1/54 (1.9%)	1
Constipation	1/116 (0.9%)	1	0/54 (0%)	0
Worstening of swallow - more difficult	1/116 (0.9%)	1	0/54 (0%)	0
General disorders
Blood in sputum	1/116 (0.9%)	1	0/54 (0%)	0
Common Cold / Fever / Not Feeling Well	2/116 (1.7%)	2	3/54 (5.6%)	3
Patient over-medicated	1/116 (0.9%)	1	0/54 (0%)	0
Unable to tolerate electrode placement it c/o dizziness	0/116 (0%)	0	1/54 (1.9%)	1
Pain related to oral biopsy	1/116 (0.9%)	1	0/54 (0%)	0
Musculoskeletal and connective tissue disorders
Tongue tingling / edema	2/116 (1.7%)	2	0/54 (0%)	0
Pain / discomfort in neck / throat	4/116 (3.4%)	5	1/54 (1.9%)	1
Respiratory, thoracic and mediastinal disorders
Coughing	3/116 (2.6%)	3	0/54 (0%)	0
Upper respiratory infection	0/116 (0%)	0	1/54 (1.9%)	1
Difficulty breathing d/t glottic stenosis	0/116 (0%)	0	1/54 (1.9%)	1
Surgical and medical procedures
Bronchoscopy for RLL infiltrate	1/116 (0.9%)	1	0/54 (0%)	0
Lung biopsy for suspicious mass	1/116 (0.9%)	1	0/54 (0%)	0

Limitations/Caveats

Because of funding limitations research assistants could not be hired at most sites, and so 170 (instead of 240) subjects were enrolled. However, the results suggest additional patients would not have changed the outcome.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.