Treatment of Chronic Laryngitis With Amitriptyline

• Sponsor: Boston Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02552225
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arms: 2
• Actual Duration (Months): 57.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This randomized, double-blind, placebo-controlled trial will compare the effectiveness of amitriptyline versus placebo (inactive medication) in treating chronic laryngitis.

Condition or Disease	Intervention/Treatment	Phase
Laryngeal Diseases	Drug: Amitriptyline; Other: Placebo	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Double-blind Placebo Controlled Trial of the Treatment of Chronic Laryngitis With Amitriptyline
• Actual Study Start Date: Apr 1, 2016
• Actual Primary Completion Date: Jan 15, 2021
• Actual Study Completion Date: Jan 15, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: amitriptyline Subjects in this arm will receive pills composed of amitriptyline and Avicel (cellulose filler)	Drug: Amitriptyline; Subjects in this arm will receive pills composed of amitriptyline and Avicel (cellulose filler); Other Names: Elavil
Placebo Comparator: placebo Subjects in this arm will receive pills composed only of Avicel (cellulose filler)	Other: Placebo; Subjects in this arm will receive pills composed only of Avicel (cellulose filler)

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Boston Medical Center	Boston	Massachusetts	United States	02118

Sponsors and Collaborators

• Boston Medical Center

Investigators

• Principal Investigator: J. Pieter Noordzij, MD, Boston Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 30, 2017

More Information

Publications

None provided.

• Responsible Party: Boston Medical Center
• ClinicalTrials.gov Identifier: NCT02552225
• Other Study ID Numbers: H 34438
• First Posted: Sep 17, 2015
• Last Update Posted: Oct 29, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Boston Medical Center: laryngeal sensory neuropathy, chronic laryngeal neuropathy
• Additional relevant MeSH terms: Laryngitis; Laryngeal Diseases; Amitriptyline

Study Results

Participant Flow

Arm/Group Title	Amitriptyline	Placebo
Arm/Group Description	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)	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)
Period Title: Overall Study
STARTED	3	3
COMPLETED	2	3
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Amitriptyline	Placebo	Total
Arm/Group Description	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)	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)	Total of all reporting groups
Overall Participants	3	3	6
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.3 (19.9)	55.0 (6.6)	53.7 (13.3)
Sex: Female, Male (Count of Participants)
Female	2 66.7%	2 66.7%	4 66.7%
Male	1 33.3%	1 33.3%	2 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 33.3%	0 0%	1 16.7%
Not Hispanic or Latino	2 66.7%	2 66.7%	4 66.7%
Unknown or Not Reported	0 0%	1 33.3%	1 16.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 66.7%	0 0%	2 33.3%
White	0 0%	2 66.7%	2 33.3%
More than one race	0 0%	1 33.3%	1 16.7%
Unknown or Not Reported	1 33.3%	0 0%	1 16.7%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	6 100%
Reflux Symptom Index (RSI) (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	21.33 (11.50)	25.67 (6.51)	23.50 (8.69)
Voice Handicap Index-10 (VHI-10) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	1.67 (2.89)	9.67 (9.5)	5.67 (7.66)
Cough Severity Index (CSI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.00 (5.66)	21.33 (12.42)	14.40 (13.24)
Throat pain/burning (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	0.0 (0.0)	3.33 (1.53)	1.67 (2.07)
Pain when swallowing (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	0.67 (1.15)	0.67 (0.58)	0.67 (0.82)

Outcome Measures

1. Primary Outcome

Title	Change in Score on Reflux Symptom Index (RSI)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Amitriptyline	Placebo
Arm/Group Description	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)	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)
Measure Participants	2	3
Mean (Standard Deviation) [score on a scale]	-2 (1.41)	-1.67 (2.08)

2. Secondary Outcome

Title	Change in the Score on the Voice Handicap Index-10 (VHI-10)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Amitriptyline	Placebo
Arm/Group Description	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)	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)
Measure Participants	2	3
Mean (Standard Deviation) [units on a scale]	8.0 (11.31)	2.67 (4.04)

3. Secondary Outcome

Title	Change in the Score on the Cough Severity Index (CSI)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Amitriptyline	Placebo
Arm/Group Description	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)	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)
Measure Participants	2	3
Mean (Standard Deviation) [units on a scale]	10 (14.14)	3.67 (5.51)

4. Secondary Outcome

Title	Change in Throat Pain or Burning
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Amitriptyline	Placebo
Arm/Group Description	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)	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)
Measure Participants	2	3
Mean (Standard Deviation) [units on a scale]	2.0 (2.83)	-1.33 (1.53)

5. Secondary Outcome

Title	Change in Pain When Swallowing
Description	Participants were asked to rate their pain when swallowing on a scale of 0=none to 5= severe pain.
Time Frame	baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Amitriptyline	Placebo
Arm/Group Description	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)	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)
Measure Participants	2	3
Mean (Standard Deviation) [units on a scale]	1.0 (4.24)	0.33 (1.53)

6. Secondary Outcome

Title	Subjective Improvement of Laryngitis Symptoms
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Amitriptyline	Placebo
Arm/Group Description	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)	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)
Measure Participants	2	3
Mean (Standard Deviation) [units on a scale]	8.0 (0)	2.0 (3.46)

7. Secondary Outcome

Title	Number of Participants Who Dropped Out of the Study Due to Side Effects
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amitriptyline	Placebo
Arm/Group Description	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)	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)
Measure Participants	3	3
Count of Participants [Participants]	1 33.3%	0 0%

Adverse Events

Time Frame	8 weeks
Arm/Group Title	Amitriptyline		Placebo
Arm/Group Description	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)		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)
All Cause Mortality
	Amitriptyline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)
Serious Adverse Events
	Amitriptyline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Amitriptyline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		1/3 (33.3%)
Cardiac disorders
Tachycardia	1/3 (33.3%)	1	0/3 (0%)	0
Gastrointestinal disorders
Indigestion	1/3 (33.3%)	1	0/3 (0%)	0
Nausea	0/3 (0%)	0	1/3 (33.3%)	1
General disorders
Dizziness	2/3 (66.7%)	2	1/3 (33.3%)	1
Chest pain	1/3 (33.3%)	1	0/3 (0%)	0
Arm weakness	1/3 (33.3%)	1	0/3 (0%)	0
Facial weakness	1/3 (33.3%)	1	0/3 (0%)	0
Insomnia	1/3 (33.3%)	1	0/3 (0%)	0
Headache	0/3 (0%)	0	1/3 (33.3%)	1
Lack of energy	0/3 (0%)	0	1/3 (33.3%)	1
Sleepy	0/3 (0%)	0	1/3 (33.3%)	1
Dry mouth	0/3 (0%)	0	1/3 (33.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/3 (33.3%)	1	0/3 (0%)	0

Limitations/Caveats

Funding was not obtained so the study could not be continued after the Covid pause.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.