Treatment of Chronic Laryngitis With Amitriptyline

Double-blind Placebo Controlled Trial of the Treatment of Chronic Laryngitis With Amitriptyline

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

Study Overview

• Status: Terminated
• Conditions: Laryngeal Diseases
• Intervention / Treatment: Drug: Amitriptyline; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	baseline, 8 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): January 15, 2021
• Study Completion (Actual): January 15, 2021

Study Registration Dates

• First Submitted: September 9, 2015
• First Submitted That Met QC Criteria: September 15, 2015
• First Posted (Estimate): September 17, 2015

Study Record Updates

• Last Update Posted (Actual): October 29, 2021
• Last Update Submitted That Met QC Criteria: October 1, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: laryngeal sensory neuropathy, chronic laryngeal neuropathy
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Laryngitis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Tricyclic; Adrenergic Uptake Inhibitors; Amitriptyline
• Other Study ID Numbers: H 34438

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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