Analgesic Effects of Topical Ketamine Mouthwash in Patients Receiving Chemoradiation or Radiotherapy for Head & Neck Cancer

Study Overview
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Brief Summary
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The primary objective is to determine the reduction in pain score by ketamine mouthwash compared to placebo in head and neck cancer patients with refractory mucositis. The secondary objectives are to describe the duration of analgesia and adverse effects associated with ketamine and placebo.

Detailed Description
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We would like to determine the effectiveness of ketamine mouthwash in providing pain relief to subjects with head and neck cancer suffering from mucositis, a common adverse event of radiation therapy and chemoradiation therapy. Ketamine is a schedule III controlled substance that is generally used to provide anesthesia for short diagnostic and surgical procedures. Ten subjects will be randomized to two treatment arms. Group A will receive ketamine on Monday, placebo on Wednesday, and ketamine on Friday. Group B will receive placebo on Monday, ketamine on Wednesday, and placebo on Friday. Each subject will swish the study drug or placebo for 2 minutes and spit it out. The use of non-maintenance mucositis medications such as DLM solution will not be allowed during the clinic visit. Subjects may resume non-maintenance mucositis medications at home. Subjects will be asked to document adverse effects and pain scores at 30, 45, and 60 minutes after study medication. The Richmond Agitation and Sedation Scale (RASS) will be used to determine a subject's sedation level, if necessary. Treatment will last for up to 6 weeks unless an illness or an event occurs that prevents continuation, intolerance to the agent, adverse events, resolution of mucositis pain, or the decision to withdraw from the study.

Official Title
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Analgesic Effects of Topical Ketamine Mouthwash in Patients Receiving Chemoradiation or Radiotherapy for Head and Neck Cancer

Conditions
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Mucositis, Head and Neck Cancer

Intervention / Treatment
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* Drug: Ketamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects diagnosed with head and neck tumors (any histology) receiving ongoing chemoradiation or radiation therapy Subjects with mucositis pain refractory to topical management, defined as any self-reported pain score of > 2 in the 24 hours prior to enrollment despite use of topical agents as prescribed Age ≥ 18 years Ability to understand and willingness to consent and to sign consent form Exclusion Criteria: Active substance abuse at time of registration (alcohol, drugs, non-prescription use of controlled substances) Subjects with history of allergic reactions to ketamine Persistent oral bleeding: > 15 mL (estimated) per day Pregnancy or breast feeding

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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ketamine<br>Twenty milligrams of ketamine will be dissolved in 4 mL of pharmaceutical cherry syrup and 1 ml of normal saline. | Drug: Ketamine<br>* Twenty milligrams of ketamine will be dissolved in 4 mL of pharmaceutical cherry syrup and 1 ml of normal saline.<br>|
| Placebo Comparator: Placebo<br>The placebo will consist of 4 ml of cherry syrup and 1 ml of normal saline. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pain Score | The primary analysis is testing and estimating the effect of ketamine in comparison to placebo. Pain assessment will be analyzed using descriptive statistics. We will determine average pain scores. Pain will be measured using a 0-10 scale with 0 representing no pain; 1-3 representing mild pain; 4-6 representing moderate pain; and 7-10 representing severe pain. The effect of ketamine in comparison to placebo will be estimated with a mean and confidence interval. Proportional changes in pain scores (post-treatment pain score ÷ pre-treatment pain score) will be calculated and similarly analyzed. The proportion of subjects experiencing a reduction in pain scores of >33% will be calculated. | After 9-10 doses, expected average 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Analgesic Effect | The secondary analysis is testing and estimating the analgesic effect of ketamine in comparison to placebo. Pain assessment will be analyzed using descriptive statistics. We will also determine average duration of analgesia. The effect of ketamine in comparison to placebo will be estimated with a mean and confidence interval. | After 9-10 doses, expected average 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mucositis, head and neck, cancer, radiation therapy, chemoradiation, oral, pain