Head and Neck Cancer, Mucositis
Conditions
Keywords
mucositis, head and neck, cancer, radiation therapy, chemoradiation, oral, pain
Brief summary
* 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
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.
Interventions
DRUGKetamine
Twenty milligrams of ketamine will be dissolved in 4 mL of pharmaceutical cherry syrup and 1 ml of normal saline.
DRUGPlacebo
Sponsors
Dartmouth-Hitchcock Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain Score | After 9-10 doses, expected average 1 month | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Analgesic Effect | After 9-10 doses, expected average 1 month | 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. |
Countries
United States
Participant flow
Recruitment details
Participant recruitment occurred between 5/24/2010-8/3/2016.
Pre-assignment details
Participants were randomized to receive ketamine (K) or placebo (P) in repeating sequences of KPK or PKP. Not all participants completed all sequences. A participant was considered complete if they received at least one dose of K or P and completed the pain assessment.
Participants by arm
| Arm | Count |
|---|---|
| Cohort All individuals participating in the trial. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Cohort |
|---|---|
| Age, Continuous | 56.45 Years |
| Region of Enrollment United States | 10 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 10 |
| other Total, other adverse events | 3 / 9 | 2 / 10 |
| serious Total, serious adverse events | 0 / 9 | 0 / 10 |
Outcome results
Primary
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.
Time frame: After 9-10 doses, expected average 1 month
Population: 1-4 pain measurements were obtained per participant. One assessment occurred per administered dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Change in Pain Score | 1.167 score on a scale | Standard Deviation 1.37 |
| Placebo | Change in Pain Score | 1.58 score on a scale | Standard Deviation 1.31 |
p-value: 0.3198t-test, 2 sided
Secondary
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.
Time frame: After 9-10 doses, expected average 1 month
Population: 1-4 measurements of analgesic effects were obtained per participant. One assessment occurred per administered dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Duration of Analgesic Effect | 39.231 minutes | Standard Deviation 11.519 |
| Placebo | Duration of Analgesic Effect | 35.357 minutes | Standard Deviation 9.499 |
p-value: 0.3522t-test, 2 sided