Laryngeal Diseases
Conditions
Keywords
laryngeal sensory neuropathy, chronic laryngeal neuropathy
Brief summary
This randomized, double-blind, placebo-controlled trial will compare the effectiveness of amitriptyline versus placebo (inactive medication) in treating chronic laryngitis.
Detailed description
Chronic laryngitis commonly manifests through symptoms including cough, hoarseness, throat clearing, foreign body sensation, throat pain, sensation of excessive phlegm, and difficulty swallowing. A significant minority also present with GERD, rhinosinusitis-induced post-nasal drainage, direct allergic effect, and smoking issues. Amitriptyline is commonly used for mental/mood problems, but is also prescribed to treat chronic laryngitis because some investigators suggest a neuropathic etiology for idiopathic chronic laryngitis. No trials have compared any treatment for chronic laryngitis to placebo and it is unknown if currently used therapies for chronic laryngitis are effective. At the baseline visit, subjects will be assigned at random to amitriptyline or placebo, which they will take for 4 weeks each. Subjects will be seen in the clinic at baseline and after 10 weeks. Improvement will be measured using standardized symptom scales, and a self-reported subjective improvement percentage.
Interventions
DRUGAmitriptyline
Subjects in this arm will receive pills composed of amitriptyline and Avicel (cellulose filler)
OTHERPlacebo
Subjects in this arm will receive pills composed only of Avicel (cellulose filler)
Sponsors
Boston Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Must be age 18 or older and able to consent for themselves 2. Must have had structural pathology such as tumor previously ruled out using flexible laryngoscopy 3. Must be able to speak and read the English language 4. Must have failed a 2 month or longer trial of a proton pump inhibitor for the treatment of gastro-esophageal reflux 5. Women under 55 years of age who may become pregnant must have a negative pregnancy test and agree to barrier or hormonal methods of contraception during the study 6. Potential subject and their physician have agreed that amitriptyline will be part of their regular care plan
Exclusion criteria
1. Active untreated environmental allergies 2. Smoking within past 5 years 3. Current upper respiratory infections 4. Use of narcotics (e.g. oxycodone, methadone) within the past week 5. Hypersensitivity to amitriptyline 6. History of amitriptyline use or of other tricyclic antidepressant - including pregabalin, gabapentin, baclofen, or other gamma-aminobutyric acid (GABA)analogues or inhibitors - for any medical condition (not limited to chronic laryngitis) within the past 12 months. 7. Use of any other monoamine oxidase inhibitors (MAOIs) other than amitriptyline within the past 4 weeks (selegiline, phenelzine, tranylcypromine, isocarboxazid, rasagiline, phenelzine sulfate, selegiline hydrochloride, rasagiline mesylate, tranylcypromine sulfate) 8. History of urinary retention 9. History of an acute episode of a major depressive disorder within the past 12 months 10. For women 18-55 years of age without history of menopause: currently nursing or pregnant, plans to become pregnant, or unwillingness to utilize contraception (barrier or hormonal methods) 11. Currently participating in another clinical trial that could interfere with the efficacy of, or participation in, this study. 12. Current untreated diagnosis of gastroesophageal reflux (GERD)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Score on Reflux Symptom Index (RSI) | baseline, 8 weeks | The Reflux Symptom Index (RSI) is a validated questionnaire consisting of 9 statements to be ranked on a scale of 0-5 (0=no problem, 5=severe problem). RSI scores can range from 0 to 45, with higher scores correlated with more reflux symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Score on the Voice Handicap Index-10 (VHI-10) | baseline, 8 weeks | The Voice Handicap Index-10 (VHI-10) is a 10-question scale rated from 0-4 that addresses effects on quality of life from voice disorders (0=never, 1=almost never, 2=sometimes, 3=almost always, 4=always). VHI-10 scores can range from 0 to 40, with lower scores correlated with a higher quality of life related to voice disorders. |
| Change in the Score on the Cough Severity Index (CSI) | baseline, 8 weeks | The Cough Severity Index is a validated 10 item questionnaire to quantify a patient's symptoms associated with upper airway chronic cough. The 4 point Likert scale for each of the 10 items is 0 to 4 where 0 = Never, 1 = Almost never, 2 = Sometimes, 3 = Almost always, 4 = Always. Scores can range from 0 to 40 and higher scores reflect more coughing. |
| Change in Throat Pain or Burning | baseline, 8 weeks | Participants will be asked to rate the severity of their throat pain or burning on a scale from 0 (no problem) to 5 (severe). Higher scores are correlated with more throat pain/burning. |
| Change in Pain When Swallowing | baseline, 8 weeks | Participants were asked to rate their pain when swallowing on a scale of 0=none to 5= severe pain. |
| Subjective Improvement of Laryngitis Symptoms | 8 weeks | Patients will subjectively rate improvement of symptoms on an ordinal 10-point scale where 0=no improvement and 10=significant improvement. |
| Number of Participants Who Dropped Out of the Study Due to Side Effects | 8 weeks | The number of patients who report they did not continue with study participation due to side effects, will be obtained from study logs. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Amitriptyline Subjects in this arm will receive pills composed of amitriptyline and Avicel (cellulose filler)
Amitriptyline: Subjects in this arm will receive pills composed of amitriptyline and Avicel (cellulose filler) | 3 |
| Placebo Subjects in this arm will receive pills composed only of Avicel (cellulose filler)
Placebo: Subjects in this arm will receive pills composed only of Avicel (cellulose filler) | 3 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo | Amitriptyline |
|---|---|---|---|
| Age, Continuous | 53.7 years STANDARD_DEVIATION 13.3 | 55.0 years STANDARD_DEVIATION 6.6 | 52.3 years STANDARD_DEVIATION 19.9 |
| Cough Severity Index (CSI) | 14.40 units on a scale STANDARD_DEVIATION 13.24 | 21.33 units on a scale STANDARD_DEVIATION 12.42 | 4.00 units on a scale STANDARD_DEVIATION 5.66 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Pain when swallowing | 0.67 units on a scale STANDARD_DEVIATION 0.82 | 0.67 units on a scale STANDARD_DEVIATION 0.58 | 0.67 units on a scale STANDARD_DEVIATION 1.15 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 0 Participants |
| Reflux Symptom Index (RSI) | 23.50 score on a scale STANDARD_DEVIATION 8.69 | 25.67 score on a scale STANDARD_DEVIATION 6.51 | 21.33 score on a scale STANDARD_DEVIATION 11.5 |
| Region of Enrollment United States | 6 participants | 3 participants | 3 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 1 Participants |
| Throat pain/burning | 1.67 units on a scale STANDARD_DEVIATION 2.07 | 3.33 units on a scale STANDARD_DEVIATION 1.53 | 0.0 units on a scale STANDARD_DEVIATION 0 |
| Voice Handicap Index-10 (VHI-10) | 5.67 units on a scale STANDARD_DEVIATION 7.66 | 9.67 units on a scale STANDARD_DEVIATION 9.5 | 1.67 units on a scale STANDARD_DEVIATION 2.89 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 2 / 3 | 1 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 |
Outcome results
Primary
Change in Score on Reflux Symptom Index (RSI)
The Reflux Symptom Index (RSI) is a validated questionnaire consisting of 9 statements to be ranked on a scale of 0-5 (0=no problem, 5=severe problem). RSI scores can range from 0 to 45, with higher scores correlated with more reflux symptoms.
Time frame: baseline, 8 weeks
Population: There was no 8 week RSI score for the participant who withdrew from the amitriptyline arm so the change in score could not be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amitriptyline | Change in Score on Reflux Symptom Index (RSI) | -2 score on a scale | Standard Deviation 1.41 |
| Placebo | Change in Score on Reflux Symptom Index (RSI) | -1.67 score on a scale | Standard Deviation 2.08 |
Secondary
Change in Pain When Swallowing
Participants were asked to rate their pain when swallowing on a scale of 0=none to 5= severe pain.
Time frame: baseline, 8 weeks
Population: There was no 8 week assessment of pain while swallowing for the participant who withdrew from the amitriptyline arm, so the change in score could not be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amitriptyline | Change in Pain When Swallowing | 1.0 units on a scale | Standard Deviation 4.24 |
| Placebo | Change in Pain When Swallowing | 0.33 units on a scale | Standard Deviation 1.53 |
Secondary
Change in the Score on the Cough Severity Index (CSI)
The Cough Severity Index is a validated 10 item questionnaire to quantify a patient's symptoms associated with upper airway chronic cough. The 4 point Likert scale for each of the 10 items is 0 to 4 where 0 = Never, 1 = Almost never, 2 = Sometimes, 3 = Almost always, 4 = Always. Scores can range from 0 to 40 and higher scores reflect more coughing.
Time frame: baseline, 8 weeks
Population: There was no 8 week CSI score for the participant who withdrew from the amitriptyline arm so the change in score could not be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amitriptyline | Change in the Score on the Cough Severity Index (CSI) | 10 units on a scale | Standard Deviation 14.14 |
| Placebo | Change in the Score on the Cough Severity Index (CSI) | 3.67 units on a scale | Standard Deviation 5.51 |
Secondary
Change in the Score on the Voice Handicap Index-10 (VHI-10)
The Voice Handicap Index-10 (VHI-10) is a 10-question scale rated from 0-4 that addresses effects on quality of life from voice disorders (0=never, 1=almost never, 2=sometimes, 3=almost always, 4=always). VHI-10 scores can range from 0 to 40, with lower scores correlated with a higher quality of life related to voice disorders.
Time frame: baseline, 8 weeks
Population: There was no 8 week VHI-10 score for the participant who withdrew from the amitriptyline arm so the change in score could not be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amitriptyline | Change in the Score on the Voice Handicap Index-10 (VHI-10) | 8.0 units on a scale | Standard Deviation 11.31 |
| Placebo | Change in the Score on the Voice Handicap Index-10 (VHI-10) | 2.67 units on a scale | Standard Deviation 4.04 |
Secondary
Change in Throat Pain or Burning
Participants will be asked to rate the severity of their throat pain or burning on a scale from 0 (no problem) to 5 (severe). Higher scores are correlated with more throat pain/burning.
Time frame: baseline, 8 weeks
Population: There was no 8 week assessment of throat pain/burning for the participant who withdrew from the amitriptyline arm, so the change in score could not be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amitriptyline | Change in Throat Pain or Burning | 2.0 units on a scale | Standard Deviation 2.83 |
| Placebo | Change in Throat Pain or Burning | -1.33 units on a scale | Standard Deviation 1.53 |
Secondary
Number of Participants Who Dropped Out of the Study Due to Side Effects
The number of patients who report they did not continue with study participation due to side effects, will be obtained from study logs.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Amitriptyline | Number of Participants Who Dropped Out of the Study Due to Side Effects | 1 Participants |
| Placebo | Number of Participants Who Dropped Out of the Study Due to Side Effects | 0 Participants |
Secondary
Subjective Improvement of Laryngitis Symptoms
Patients will subjectively rate improvement of symptoms on an ordinal 10-point scale where 0=no improvement and 10=significant improvement.
Time frame: 8 weeks
Population: There was no 8 week assessment of subjective assessment of laryngitis symptoms for the participant who withdrew from the amitriptyline arm, so it could ot be reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amitriptyline | Subjective Improvement of Laryngitis Symptoms | 8.0 units on a scale | Standard Deviation 0 |
| Placebo | Subjective Improvement of Laryngitis Symptoms | 2.0 units on a scale | Standard Deviation 3.46 |