We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Acupuncture-Like Transcutaneous Electrical Nerve Stimulation (ALTENS) or Pilocarpine in Treating Early Dry Mouth in Patients Undergoing Radiation Therapy for Head and Neck Cancer

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00656513
First Posted: April 11, 2008
Last Update Posted: August 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
  Purpose

RATIONALE: Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) and pilocarpine may help to relieve chronic xerostomia (dry mouth). It is not yet known which remedy is more effective in treating chronic dry mouth caused by radiation therapy in patients with head and neck cancer.

PURPOSE: This randomized phase II/III trial is studying ALTENS to see how well it works compared with pilocarpine in treating chronic dry mouth caused by radiation therapy in patients with head and neck cancer.


Condition Intervention Phase
Head and Neck Cancer Xerostomia Drug: Pilocarpine Procedure: ALTENS Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
One arm Phase II followed by a two-arm Phase III
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: A Phase II/III Study Comparing Acupuncture-like Transcutaneous Electrical Nerve Stimulation (ALTENS) Versus Pilocarpine in Treating Early Radiation-Induced Xerostomia

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Phase II: Treatment Compliance (Number of Compliant Patients) [ Time Frame: Randomization to 12 weeks ]
    Patients completing at least 19 out of 24 ALTENS therapy sessions were categorized as compliant. Fleming's two-stage was used, assuming a successful target compliance rate of 80%, statistical power of 0.87, and a type I error rate of 0.13. If fewer than 9 of the first 13 patients were compliant, then treatment delivery will be deemed not feasible. If there were between 9-12 compliant patients, the second stage analysis would be required to determine feasibility of treatment delivery. If all 13 patients are compliant, treatment delivery will immediately be deemed feasible. The second stage analysis required at least 31 compliant out of 39 overall patients for the treatment delivery to be deemed feasible.

  • Phase III: Change From Baseline in Overall Xerostomia Burden at 9 Months [ Time Frame: Baseline (randomization) and 9 months ]
    Xerostomia burden is measured by the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning.The score is the average of all responses of all domains and can range from 0 to 4, with higher scores indicating increased xerostomia burden. Change in xerostomia burden is calculated by subtracting the baseline score from the 9-month score such that a negative change indicates an improvement of the xerostomia burden.


Secondary Outcome Measures:
  • Phase II: Pecentage of Patients With Beneficial Treatment Response [ Time Frame: Pre-treatment and 6 months from registration ]
    This secondary objective was to evaluate the effect of ALTENS treatment on overall radiation-induced xerostomia burden by looking at treatment response. Treatment response was determined by a reduction of at least 20% from baseline to 6 months in the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning.The score is the average of all responses of all domains and can range from 0 to 4. Higher scores indicate increased xerostomia burden. This scale has high reproducibility and sensitivity. For the first and second stage analyses, 4 and 10 patients, respectively, must respond to treatment in order to proceed to the phase III component.

  • Change From Baseline in Overall Xerostomia Burden at 4, 6, and 15 Months (Phase III) [ Time Frame: Baseline, 4, 6, and 15 months from randomization ]
    Xerostomia burden is measured by the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning.The score is the average of all responses of all domains and can range from 0 to 4, with higher scores indicating increased xerostomia burden. Change in xerostomia burden is calculated by subtracting the baseline score from the 9-month score such that a negative change indicates an improvement of the xerostomia burden.

  • Change From Baseline in Symptom Burden at 4, 6, 9 and 15 Months (Phase III) [ Time Frame: Baseline, 4, 6, 9 and 15 months from randomization ]
    Symptom burden is measured by the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS). The XeQOLS is a validated patient-reported 15-item assessment scale with 4 domains: physical functioning,pain/discomfort, personal/psychologic functioning, and social functioning. The domain score is the average of all responses on a given domain and can range from 0 to 4, with higher scores indicating increased symptom burden. Change in symptom burden is calculated by subtracting the baseline score from the 9-month score such that a negative change indicates an improvement of the symptom burden.

  • Change From Baseline in Stimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) [ Time Frame: Baseline, 4, 6, 9 and 15 months from randomization ]
    Stimulated (citric acid primed) whole salivary production (WSP) was measured by expectoration weight, with one gram of saliva produced considered as one ml of saliva. WSP is expressed in ml/min calculated by dividing the measured weight or volume of WSP by five. Procedure: Patients refrain from eating, drinking, and smoking at least two hours prior to each measurement. Stimulation is elicited by asking patients to rinse 5 ml of 2% citric acid solution in the mouth for 15 seconds and then completely expectorating the citric acid. For each measurement, patients are asked to expectorate continuously into a pre-weighed dry plastic container over a 5-minute period without swallowing. The collected saliva with the plastic container will be weighed (total weight) immediately after each collection. The total weight minus the weight of the container is the weight or volume of whole saliva collected.

  • Change From Baseline in Unstimulated Whole Salivary Production (WSP) at 4, 6, 9 and 15 Months (Phase III) [ Time Frame: Pre-treatment to 4, 6, 9 and 15 months from randomization ]
    Basal whole salivary production (WSP) was measured by expectoration weight, with one gram of saliva produced considered as one ml of saliva. WSP is expressed in ml/min calculated by dividing the measured weight or volume of WSP by five. Procedure: Patients refrain from eating, drinking, and smoking at least two hours prior to each measurement. For each measurement, patients are asked to expectorate continuously into a pre-weighed dry plastic container over a 5-minute period without swallowing. The collected saliva with the plastic container will be weighed (total weight) immediately after each collection. The total weight minus the weight of the container is the weight or volume of whole saliva collected.

  • Quality of Life (QOL) as Measured by the University of Washington Head and Neck Questionnaire (UWHNSS) Phase III [ Time Frame: Baseline and 9 months from randomization. ]
    The UWHNSS includes ten categories—pain, disfigurement, activity, recreation/entertainment, employment, eating, saliva, taste, speech, mucus/phlegm. Patient scores on the UWHNSS range from 0 to 100 with higher scores indicating declining quality of life. Change in total score was calculated by subtracting baseline from follow-up , thus a positive change score indicates a worsening while a negative change score indicates an improvement.


Enrollment: 196
Study Start Date: September 2008
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Pilocarpine: Phase III Drug: Pilocarpine
5mg by mouth 3 times a day for 12 weeks
Other Name: pilocarpine hydrochloride
Experimental: ALTENS: Phase III Procedure: ALTENS
Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit
Other Name: acupuncture-like transcutaneous electrical nerve stimulation
Experimental: ALTENS: Phase II Procedure: ALTENS
Acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) twice weekly for 12 weeks via a Codetron unit
Other Name: acupuncture-like transcutaneous electrical nerve stimulation

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of head and neck cancer

    • No clinical evidence of disease recurrence by ear, nose, and throat exam with a nasopharyngeal scope, if indicated, 8 weeks prior to registration
  • Completed radiotherapy (i.e., standard or intensity-modulated radiotherapy) with or without chemotherapy ≥ 3 months and up to 2 years prior to study entry

    • Grade 1-2 radiotherapy-induced xerostomia according to the NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v.3.0 and the dry mouth/salivary gland xerostomia scale
    • Must have evidence of residual salivary function with unstimulated (basal) whole salivary production ≥ 0.1 ml/min after having refrained from eating or drinking oral fluid for 2 hours
  • No patients with normal saliva production (i.e., no salivary gland changes or no xerostomia)
  • No history of serious adverse events after prior treatment with and discontinuation of pilocarpine
  • No chronic lymphocytic leukemia

PATIENT CHARACTERISTICS:

  • See Disease Characteristics
  • Zubrod performance status of 0-2
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other invasive malignancy except non-melanomatous skin cancer or cancer from which the patient has been disease-free for at least 3 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix)
  • No concurrent contraindications to pilocarpine (e.g., uncontrolled asthma, miosis, or hypersensitivity)
  • No severe, active co-morbidity, including any of the following:

    • Unstable cardiac disease or requirement for a pacemaker in-situ
    • Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
    • Transmural myocardial infarction within the past 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • No Sjögren syndrome

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 2 weeks since prior pilocarpine or cevimeline and no concurrent use for ophthalmic or non-ophthalmic indications
  • No concurrent regular medications that induce xerostomia (e.g., tricyclic antidepressants, antihistamines with anticholinergic effects, or narcotics)
  • No concurrent oral stimulating agents or salivary gland medical stimulants
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00656513


Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Connecticut
Hospital of Saint Raphael
New Haven, Connecticut, United States, 06511
United States, Georgia
Emory Crawford Long Hospital
Atlanta, Georgia, United States, 30308
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Saint Anthony's Hospital at Saint Anthony's Health Center
Alton, Illinois, United States, 62002
United States, Indiana
Bloomington Hospital Regional Cancer Institute
Bloomington, Indiana, United States, 47403
Center for Cancer Care at Goshen General Hospital
Goshen, Indiana, United States, 46526
Methodist Cancer Center at Methodist Hospital
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Boston University Cancer Research Center
Boston, Massachusetts, United States, 02118
United States, Missouri
CCOP - St. Louis-Cape Girardeau
Saint Louis, Missouri, United States, 63141
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
United States, North Carolina
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States, 28232-2861
United States, Ohio
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
United States, Oklahoma
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, United States, 73104
United States, West Virginia
Schiffler Cancer Center at Wheeling Hospital
Wheeling, West Virginia, United States, 26003
Canada, Quebec
Maisonneuve-Rosemont Hospital
Montreal, Quebec, Canada, H1T 2M4
Hopital Notre-Dame du CHUM
Montreal, Quebec, Canada, H2L 4M1
McGill Cancer Centre at McGill University
Montreal, Quebec, Canada, H2W 1S6
Centre Hospitalier Universitaire de Quebec
Quebec City, Quebec, Canada, G1R 2J6
Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
NRG Oncology
Investigators
Principal Investigator: Raimond K. W. Wong, MD Margaret and Charles Juravinski Cancer Centre
  More Information

Publications:
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00656513     History of Changes
Other Study ID Numbers: RTOG-0537
CDR0000592644
First Submitted: April 10, 2008
First Posted: April 11, 2008
Results First Submitted: June 22, 2017
Results First Posted: August 21, 2017
Last Update Posted: August 21, 2017
Last Verified: July 2017

Keywords provided by Radiation Therapy Oncology Group:
hypopharyngeal cancer
laryngeal cancer
lip and oral cavity cancer
nasopharyngeal cancer
paranasal sinus and nasal cavity cancer
oropharyngeal cancer
salivary gland cancer
metastatic squamous neck cancer with occult primary
xerostomia
tongue cancer

Additional relevant MeSH terms:
Head and Neck Neoplasms
Xerostomia
Neoplasms by Site
Neoplasms
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Pilocarpine
Miotics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Muscarinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action