Effect of Topical Morphine (Mouthwash) on Oral Pain Due to Chemo- and/or Radiotherapy Induced Mucositis

Introduction:

Oral pain due to mucosal lesion is quite frequent in oncology, geriatric as well as palliative care settings. The oncology patient is mainly suffering from radio- and/or chemotherapy induced oral mucositis. The incidence of oral mucositis in oncology patients ranges from 15-40% in those receiving stomatotoxic chemotherapy or radiotherapy. The degree of mucositis is variable, but the associated pain is frequent and well documented. Nowadays, basic oral care protocols are the mainstay of preventing or reducing mucositis pain. Pain is mainly managed by systemically administered analgesia. The only pioneer work in the field of radio-or chemotherapy induced mucositis treatment with topical opioids has been done by Cerchietti in two pilot studies: one compared "magic" mouthwash (lidocaine, diphenhydramine, magnesium aluminium hydroxide) with morphine mouthwash in a randomized trial; the other compared 1%o and 2% morphine solutions in an open trial. The results showed a significant decrease in the duration of pain, the intensity as well as a decrease the need for systemic analgesia in the group with morphine mouthwash. No systemic clinically relevant adverse effects were noted.

Hypothesis:

Mouthwashes with a morphine containing solution decrease oral pain substantially, while not causing the side effects seen in systemic administration of narcotic analgesics.

Method:

A randomised double-blind cross-over study to evaluate the effect of topical oral application of a 0.2% morphine solution in patients suffering from radio- and/or chemotherapy induced oral mucositis. 60 patients will be included. Randomly assigned to either the morphine solution or a placebo mouthwash, they receive the first three days one of the solutions and then are switched over to the other treatment for three more days. General basic oral care is offered to all of the patients. Efficacy of treatment will be measured with a self-assessment pain scale. Doses of systemic opioids and other symptoms (appetite, dysphagia) will also be measured. If patient's don't receive systemic opioids, serum concentrations of morphine will be measured.

Study Overview

• Status: Completed
• Conditions: Cancer; Mucositis
• Intervention / Treatment: Drug: placebo; Drug: mouth wash with morphine

Detailed Description

randomised double-blind cross-over study to evaluate the effect of topical oral application of a 0.2% morphine solution in patients suffering from radio- and/or chemotherapy induced oral mucositis. 60 patients will be included. Randomly assigned to either the morphine solution or a placebo mouthwash, they receive the first three days one of the solutions and then are switched over to the other treatment for three more days. General basic oral care is offered to all of the patients. Efficacy of treatment will be measured with a self-assessment pain scale. Doses of systemic opioids and other symptoms (appetite, dysphagia) will also be measured. If patient's don't receive systemic opioids, serum concentrations of morphine will be measured.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Collonge-bellerive
    • Geneva, Collonge-bellerive, Switzerland, 1245
      • University Hospital Geneva

Participation Criteria

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:

• Hospitalised patients, or ambulatory patients that have daily radiotherapy in HUG
• No risk of swallowing the mouth wash solution (determined before inclusion by a recovery of more than 90% of the 15ml of water solution used for testing)
• Treatment with chemo- and/or radiotherapy causing oral mucositis
• Oral pain associated with mucosal injury (WHO grading of mucositis >= 2)
• Cognition: Mini Mental Status Examination of at least 28/30

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 1; D1-D3 receive placebo	Drug: placebo; placebo solution Quinine diHCl 0.3% at 50 mg/15 ml mouthwash 6 time/day
Active Comparator: 2; receive D1 D3 morphine	Drug: mouth wash with morphine; morphine solution 0.2% concentration; 15ml per unit mouthwash 6 time à day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
difference of pain alleviation in the two branches one hour after mouthwash and as well as the duration of pain relief.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
the requirement of supplementary systemic analgesics	1 year

Collaborators and Investigators

• Sponsor: University Hospital, Geneva
• Investigators: Principal Investigator: Sophie Pautex, MD, University Hospital, Geneva

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: January 31, 2008
• First Submitted That Met QC Criteria: February 12, 2008
• First Posted (Estimate): February 13, 2008

Study Record Updates

• Last Update Posted (Estimate): January 13, 2010
• Last Update Submitted That Met QC Criteria: January 12, 2010
• Last Verified: January 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Mucositis; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: 06-165/psy06-033