Study of the Effectiveness of Cevimeline on Oral Health in Patients With Radiation Induced Xerostomia (SMILE)

An Investigator-Initiated,Multicenter,Randomized,Double-Blind Placebo-Controlled Design Study to Assess the Effectiveness of CeviMeline to Improve OraL Health in Patients With XErostomia Secondary to Radiation Therapy for Treatment of Head and Neck Squamous Cell Carcinoma

The purpose of this study is to determine the effectiveness of cevimeline (versus placebo) on the oral health of patients who have dry mouth which was caused by radiation therapy that was given for treatment of head and/or neck cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Treatment of advanced head and neck squamous cell carcinoma (SCCA) requires aggressive therapy often combining surgical interventions with radiation therapy. Besides surveillance for persistent or recurrent cancer, clinicians seek to help minimize the side effects resulting from these aggressive treatments. Xerostomia, or "dry mouth", impacts each patient's long term health and quality of life due to the significant and diverse health consequences of having too little saliva. Normal swallowing, speaking, resistance to infection, and taste acuity are health domains that are affected by dry mouth. Psycho-social functioning decreases for many of these patients due to the extra effort to communicate and socialize (Locker D 2004).

Xerostomia is often a consequence of radiation treatment (XRT), especially when the XRT fields encompass the parotid glands and submandibular glands bilaterally. The disability and consequences of xerostomia extend beyond dysphagia, poor appetite secondary to difficulty of mastication, and loss of taste (Chambers et al. Xerostomia 2004). Since saliva is essential to normal oral flora and healthy teeth, the lack of saliva in these patients can dramatically and rapidly result in a decline of the patient's oral health. Dental complications can occur and present significant ongoing medical and surgical problems.

Our study proposes to use the Oral Health Impact Profile, OHIP-49, to measure disease-specific quality of life and functional outcomes due to radiation related xerostomia in head and neck cancer patients. The evaluation of patient QOL concomitantly with patient functioning as proposed in the SMILE protocol is an "evidence study to evaluate treatment effectiveness". The use of patient-oriented outcome measures are increasingly important to health insurers and government, but these measures are also aligned with the World Health Organization's mandate that health is a resource to manage which must be utilized and preserved so that individuals experience and gain satisfaction from living (Epstein J.1986). The OHIP-49 is patient reported outcome measure which is publicly available, validated in adult populations world-wide, and can be used an effectiveness measure. The questions are easy to answer and are based upon a 5 level likert type scale reflecting frequency of "bother" within individual psychosocial domains.

Study Type

Interventional

Enrollment (Actual)

54

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Colorado
      • Colorado Springs, Colorado, United States
    • Illinois
      • Urbana, Illinois, United States, 61801
        • Carle Clinic Association
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Commonwealth Ear, Nose and Throat
    • Pennsylvania
      • Palmyra, Pennsylvania, United States, 17078
        • Associated Otolaryngologist
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh
    • Virginia
      • Warrenton, Virginia, United States, 20186
        • Fauquier ENT Consultants

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subject is at least 18 years old and able to give written informed consent
  • Subject has received external beam radiotherapy > 4000 cGy for SCCA of the head and/or neck
  • Radiation therapy was completed at least 16 weeks (4 months) prior to enrollment into the study but not greater than 52 weeks (12 months)
  • Radiation included at least three of four of the major salivary glands (submandibular and parotid glands) in the initial field (boost fields may or may not include the parotid gland)
  • Primary therapy was designed with curative intent. Surgery is permitted if the remaining inclusion criteria are met
  • Grade 1 or 2 xerostomia by CTC version 3.0 criteria (Appendix D)
  • Demonstratable salivary flow as assessed by the clinician after administration of a potent sialogogue such as lemon juice (1 teaspoon)
  • Subject has at least one anatomically intact parotid gland and one submandibular gland
  • ECOG performance status of 0, 1, or 2
  • An EKG obtained has been performed in the past 6 months showing no arrhythmias or contraindication to administration of a muscarinic agent AND there has been no interval change in cardiac health
  • Subject is able to eat an oral diet to maintain adequate hydration and nutrition
  • Subject has provided informed consent
  • Subject is English speaking and of sufficient mental capacity to comply with the study requirements
  • Female subjects of child bearing potential have a negative serum pregnancy test and agree to use an approved method of birth control

Exclusion Criteria:

  • Subject has a life expectancy less than 12 months.
  • Subject is known or suspected to have persistent disease after curative intent
  • Subject is greater than 12 months out from completion of radiation therapy
  • Subject is pregnant or nursing
  • Subject had previous cancer of the head and/or neck and is being treated with a second course of radiation therapy
  • Subject has a history of an autoimmune disease with pretreatment xerostomia (i.e. Sjogrens) or other underlying systemic illness known to cause xerostomia independent of prior radiation therapy exposure
  • Subject has had resection of both parotid glands
  • Subject has history of cardiomyopathy or untreated moderate to severe CAD
  • Subject has known cardiac arrhythmias
  • Subject has grade 3 xerostomia (CTC v.3)or no demonstratable salivary flow after the test dose by visual inspection
  • Subject has history of significant renal or hepatic impairment
  • Subject uses a gastrostomy tube for nutrition supplementation
  • Subject is taking medications specified in Appendix C
  • Subject is taking or has taken any investigational new drug within the last 30 days or is planning to take such a drug during the course of this study
  • Subject has a contraindication to administration of muscarinic medications.
  • Subject has been treated previously with a muscarinic agent for xerostomia (i.e., Pilocarpine HCl)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
sugar pill
Other Names:
  • evoxac
Experimental: Cevimeline
Evoxac tid for xerostomia
Other Names:
  • evoxac

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To assess the impact of increased salivary flow due to treatment with cevimeline compared to placebo in patient reported oral health using the OHIP-49
Time Frame: 6 weeks
6 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
To evaluate if increased salivary flow due to cevimeline treatment results in improved patient reported quality of life using the UW-QOL-HN
Time Frame: 6 weeks
6 weeks
To evaluate which subscales of the OHIP-49 are improved most by increased salivary flow due to cevimeline treatment
Time Frame: 6 weeks
6 weeks
To evaluate which subscales of the UW-QOL-HN are improved most by increased salivary flow due to cevimeline treatment
Time Frame: 6 weeks
6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: David Witsell, MD, Duke University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2007

Primary Completion (Actual)

June 1, 2009

Study Completion (Actual)

August 1, 2009

Study Registration Dates

First Submitted

April 23, 2007

First Submitted That Met QC Criteria

April 23, 2007

First Posted (Estimate)

April 24, 2007

Study Record Updates

Last Update Posted (Estimate)

May 22, 2014

Last Update Submitted That Met QC Criteria

May 21, 2014

Last Verified

May 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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