Efficacy of Two Doses of Duloxetine and Amitriptyline in Subjects With Refractory Chronic Cough

NCT05110144 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 21-008116
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is evaluating the effectiveness of escalating doses of Amitriptyline and Duloxetine in reducing cough frequency in patients with refractory chronic cough (RCC)

Conditions

Refractory Chronic Cough

Keywords

Cough; Chronic cough; asthma; GERD; Upper airway cough syndrome; antitussives; cough hypersensitivity; refractory cough; neurogenic cough; Gastroesophageal reflux; Chronic rhinosinusitis; refractory

Outcome Measures

Primary Outcomes (1)

• Change in awake objective cough frequency (at 4 & 8 weeks)

  The primary objective is to evaluate awake cough frequency at 4 and 8 weeks using the Leicester Cough Monitor. The acoustic cough monitor recordings will be analyzed using the Leicester Cough Monitor program V2.3-MB. This will also be performed at months 4, 6, 9 \& 12 for subjects who choose to continue with the optional unblinded continuation of the study after the initial 8 weeks.

  4 weeks, 8 weeks

Secondary Outcomes (4)

• Change in 24-Hour cough frequency

  4 weeks, 8 weeks

• Change in Cough Severity Diary score

  4 weeks, 8 weeks

• Change from Baseline in Leicester Cough Questionnaire (LCQ-acute) individual domain and total scores

  4 weeks, 8 weeks

• Change in Cough Severity Visual Analogue Scale (VAS)

  4 weeks, 8 weeks

Study Arms (5)

Duloxetine and Placebo

EXPERIMENTAL

Subjects will receive 30mg of Duloxetine for blinded period 1 (first 4 week treatment period) and 30mg of Duloxetine plus 30mg Placebo for blinded period 2 (additional 4 week treatment period). After this, subjects will be unblinded and receive routine clinical care for follow up phase (up to 52 weeks).

Drug: Duloxetine 30 MG; Drug: Placebo 30 MG

Duloxetine dose escalation

EXPERIMENTAL

Subjects will receive 30mg of Duloxetine for blinded period 1 (first 4 week treatment period) and 60mg of Duloxetine for blinded period 2 (additional 4 weeks treatment period). After this, subjects will be unblinded and receive routine clinical care for follow up phase (up to 52 weeks).

Drug: Duloxetine 30 MG; Drug: Duloxetine 60 MG

Amitriptyline and Placebo

EXPERIMENTAL

Subjects will receive 25mg of Amitriptyline for blinded period 1 (first 4 week treatment period) and 25mg of Amitriptyline plus 30mg Placebo for blinded period 2 (additional 4 week treatment period). After this, subjects will be unblinded and receive routine clinical care for follow up phase (up to 52 weeks).

Drug: Amitriptyline 25 MG; Drug: Placebo 30 MG

Amitriptyline dose escalation

EXPERIMENTAL

Subjects will receive 25mg of Amitriptyline for blinded period 1 (first 4 week treatment period) and 50mg of Amitriptyline for blinded period 2 (additional 4 weeks treatment period). After this, subjects will be unblinded and receive routine clinical care for follow up phase (up to 52 weeks).

Drug: Amitriptyline 25 MG; Drug: Amitriptyline 50 MG

Placebo

PLACEBO COMPARATOR

Subjects will receive 30mg of Placebo for blinded period 1 (first 4 week treatment period) and 60mg of Placebo for blinded period 2 (additional 4 weeks treatment period). After this, subjects will be unblinded and receive routine clinical care for follow up phase (up to 52 weeks).

Drug: Placebo 30 MG; Drug: Placebo 60 MG

Interventions

Duloxetine 30 MG DRUG

30mg orally for 4 weeks

Duloxetine and Placebo; Duloxetine dose escalation

Duloxetine 60 MG DRUG

60mg orally for 4 weeks

Duloxetine dose escalation

Amitriptyline 25 MG DRUG

25 mg orally for 4 weeks

Amitriptyline and Placebo; Amitriptyline dose escalation

Amitriptyline 50 MG DRUG

50 mg orally for 4 weeks

Amitriptyline dose escalation

Placebo 30 MG DRUG

30mg tablet with no active study ingredient for 4 weeks

Amitriptyline and Placebo; Duloxetine and Placebo; Placebo

Placebo 60 MG DRUG

60mg tablet with no active study ingredient for 4 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chest radiograph or computed tomography (CT) of the thorax within the last 1 year not demonstrating any abnormality considered to be significantly contributing to the refractory chronic cough in the opinion of the Principal Investigator
• Have a diagnosis of refractory chronic cough or unexplained cough for at least one year according to the American College of Chest Physicians guidelines
• Have a score of ≥ 40mm on the Cough Severity VAS at Screening.
• Women of child-bearing potential must agree to use 2 forms of acceptable birth control and make no donation of eggs from Screening through the end of the 8-week study period. Acceptable birth control methods include established use of oral, injected, or implanted hormonal methods of contraception; intrauterine device (IUD) or intrauterine system (IUS); tubal ligation; or male sterilization. Double-barrier method (diaphragm for female subject and condom for male partner with spermicidal) satisfies the requirement for 2 forms of acceptable birth control. When concordant with the preferred lifestyle of the subject, true and complete abstinence (not periodic abstinence) is acceptable.
• Male subjects and their partners of child-bearing potential must use 2 methods of acceptable birth control, 1 of which must be a barrier method, and make no donation of sperm from Screening until 3 months after the last dose of study drug at the end of 8 weeks.
• Have provided written informed consent.
• Are willing and able to comply with all aspects of the protocol.

You may not qualify if:

• Current smoker (cigarettes, e-cigarettes or marijuana) or former smokers who have smoked within the past 12 months.
• Former smokers with \> 20 pack-year history of smoking
• Ongoing treatment with an ACE-inhibitor that is considered as the potential cause of a subject's cough or requiring treatment with an ACE-inhibitor during the study or within 12 weeks prior to the Screening/Baseline Visit (Day -14 to Day 0).
• FEV1/FVC \< 60%.
• History of upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Screening/Baseline Visit (Day -14 to Day 0)
• History of opioid use specifically prescribed for chronic cough within 2 weeks of the Screening/Baseline Visit (Day -14 to Day 0). Use of opioids for other indications (for example, to treat pain) is permitted.
• History of baclofen use specifically prescribed for chronic cough within 2 weeks of the Screening/Baseline Visit (Day -14 to Day 0). Use of baclofen for other indications (for example, to treat spasticity) is permitted.
• Diagnosis of COPD, bronchiectasis, interstitial lung disease or cystic fibrosis
• Presence of an untreated or undertreated cause for the patient's chronic cough (as determined by the treating/referring physician per ACCP guidelines). e.g. uncontrolled asthma, GERD or post-nasal drainage that could potentially explain the patient's chronic cough.
• Requiring concomitant therapy with prohibited medications (outlined below)
• Treatment with any pharmaceutical or biological investigational therapy (excluding coronavirus disease of 2019 (COVID) vaccination and COVID related monoclonal antibody therapy)
• Participation in another clinical trial that does not allow co-enrollment within 4 weeks prior to the Screening/Baseline Visit (Day -14 to Day 0)
• Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3x the upper limit of normal (ULN) during screening.
• Serum creatinine \< 30 mL/min, hemodialysis or peritoneal dialysis
• Advanced liver disease as defined by the presence of cirrhosis and/or signs of portal hypertension

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Chronic Cough; Cough; Asthma; Gastroesophageal Reflux; upper airway cough syndrome

Interventions

Duloxetine Hydrochloride; Amitriptyline

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Bronchial Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Vivek N Iyer, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: During the initial 8- week period, this will be a double-blind study. Both subjects and all study personnel (except for the research pharmacist) will be blind to the treatment assignment. Unblinding for both subjects and study investigators will occur at the end of the 8-week blinded treatment period. The subjects and all personnel involved with the conduct and the interpretation of the study, including the Investigators and other study personnel (except the research pharmacist) will be blinded to the treatment codes. Randomization data will be kept strictly confidential by the study statistician, and accessible only to authorized persons until the time of unblinding. Only in the case of an emergency, when knowledge of the investigational product is essential for the welfare of a subject, the principal investigator may unblind a subject's treatment assignment during the 8-week blinded treatment period.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A total of 50 subjects who meet entry criteria will be randomly assigned in a 1: 1: 1: 1: 1 ratio to one of five treatment arms using stratified randomization in blocks of 10. Each arm will have two successive 4-week treatment periods (Blinded Period 1 \& 2). After this, patients will be unblinded and receive routine clinical care. Participation in the unblinded portion of the study is optional.

Study Record Dates

• First Submitted: November 3, 2021
• First Posted: November 5, 2021
• Study Start: November 1, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)