Treatment of Chronic Laryngitis With Amitriptyline

• ClinicalTrials.gov Identifier: NCT02552225
• Recruitment Status: Enrolling by invitation
• First Posted: September 17, 2015
• Last Update Posted: October 22, 2019
• Sponsor: Boston Medical Center
• Collaborator: American Laryngological Association
• Information provided by (Responsible Party): Boston Medical Center

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 (Clinical Trial)
• Estimated Enrollment: 138 participants
• Allocation: Randomized
• Intervention Model: Crossover 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: April 2016
• Estimated Primary Completion Date: October 2022
• Estimated Study Completion Date: October 2022

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 Name: 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. Score on modified Reflux Symptom Index (RSI) [ Time Frame: 10 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). The RSI has been modified with the addition of two statements ("throat pain or burning" and "pain with swallowing") since those may be relevant to chronic laryngeal neuropathy. Patients will answer the questionnaire based on any symptoms they have been experiencing within the last month.

Secondary Outcome Measures :

1. Score on modified Voice Handicap Index-10 (VHI-10) [ Time Frame: 10 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).
2. Number of patients with side effects [ Time Frame: 10 weeks ]
   Count of patients who report side effects due to the treatment.
3. Number of patients discontinuing treatment due to side effects [ Time Frame: 10 weeks ]
   Count of patients who discontinue treatment and drop out of study due to the treatment side effects.
4. Subjective percentage improvement in symptoms [ Time Frame: 10 weeks ]
   Patients will subjectively rate improvement in symptoms by percentage by comparing pre-treatment (baseline) to post-treatment symptoms after 8 weeks. Patients will report if symptoms ar ebetter, worse, or same after treatment.
5. Frequency of side effect by category [ Time Frame: 10 weeks ]
   Patients will describe subjective side effects experienced, such as dry mouth, sedation, and dizziness.
6. Score on the Cough Severity Index [ Time Frame: 10 weeks ]
   The Cough Severity Index is a validated questionnaire using a 10-item likert scale to quantify a patient's symptoms associated with upper airway chronic cough.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Exclusion Criteria:

1. Environmental allergies
2. Smoking within past 5 years
3. Upper respiratory infections within the past 2 months
4. Use of narcotics (e.g. oxycodone, methadone) within the past week
5. Any prior history of amitryptiline use
6. Use of any other monoamine oxidase inhibitors (MAOIs) other than amitryptiline within the past 4 weeks (selegiline, phenelzine, tranylcypromine, isocarboxazid, rasagiline, phenelzine sulfate, selegiline hydrochloride, rasagiline mesylate, tranylcypromine sulfate)
7. History of urinary retention
8. Any history of major depressive disorder
9. Any prior history of allergy to a tricyclic antidepressant
10. Current diagnosis of gastroesophageal reflux (GERD)
11. 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)

Contacts and Locations

Locations

United States, Massachusetts

Boston Medical Center

Boston, Massachusetts, United States, 02118

Sponsors and Collaborators

Boston Medical Center

American Laryngological Association

Investigators

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

More Information

• Responsible Party: Boston Medical Center
• ClinicalTrials.gov Identifier: NCT02552225 History of Changes
• Other Study ID Numbers: H 34438
• First Posted: September 17, 2015
• Last Update Posted: October 22, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• 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:

Amitriptyline; Amitriptyline, perphenazine drug combination; Laryngitis; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Otorhinolaryngologic Diseases; Antidepressive Agents, Tricyclic; Antidepressive Agents; Psychotropic Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Adrenergic Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Adrenergic Agents; Neurotransmitter Agents; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants