Efficacy of Two Doses of Duloxetine & Amitriptyline in Interstitial Lung Disease-related Cough
- Conditions
- Interstitial Lung Disease
- Interventions
- Drug: Duloxetine 30 MGDrug: Placebo 30 MGDrug: Amitriptyline 25 MGDrug: Duloxetine 60 MGDrug: Amitriptyline 50 MGDrug: Placebo 60 MG
- Registration Number
- NCT05120934
- Lead Sponsor
- Mayo Clinic
- Brief Summary
This research study is evaluating the effectiveness of escalating doses of Amitriptyline and Duloxetine in reducing cough frequency in patients with interstitial lung disease (ILD)-related cough.
- Detailed Description
This is a randomized, double-blind, placebo-controlled, parallel-arm, dose escalation study of Duloxetine \& Amitriptyline in subjects with interstitial lung disease-related chronic cough. Subjects will be screened during a period of up to 2 week and will undergo screening/ baseline cough monitoring. A total of 25 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 5. 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. During the unblinded (routine clinical care) follow up phase; subjects will be initially offered the option of continuing amitriptyline or duloxetine based on their initial randomization arm. Subjects could also choose an alternative chronic cough therapy (e.g. pregabalin, gabapentin, 1% tetracaine lollipop or nebulized lidocaine or combination therapy).
Subjects in treatment arm 5, who received placebo during the 8 weeks blinded period will have a discussion regarding all available cough therapies. Patients will be offered the flexibility of therapy options during the unblinded follow up as they would during routine clinical care. Participation in the unblinded follow-up period will be optional.
Treatment Arm 1:
Blinded Period 1 (1st 4 weeks): 30mg of Duloxetine Blinded Period 2 (2nd 4 weeks): 30mg of Duloxetine \& 30mg of Placebo Unblinded (routine clinical care) follow up period: (up to 52 weeks): Subjects will be offered routine clinical care management for their chronic cough
Treatment Arm 2:
Blinded Period 1 (1st 4 weeks): 30mg of Duloxetine Blinded Period 2 (2nd 4 weeks): 60mg of Duloxetine (2 pills of 30mg each) Unblinded (routine clinical care) follow up period: (up to 52 weeks): Subjects will be offered routine clinical care management for their chronic cough
Treatment Arm 3:
Blinded Period 1 (1st 4 weeks): 25mg of Amitriptyline Blinded Period 2 (2nd 4 weeks): 25mg of Amitriptyline + 25mg of Placebo Unblinded (routine clinical care) follow up period: (up to 52 weeks): Subjects will be offered routine clinical care management for their chronic cough
Treatment Arm 4:
Blinded Period 1 (1st 4 weeks): 25mg of Amitriptyline Blinded Period 2 (2nd 4 weeks): 50mg of Amitriptyline (2 pills of 25mg each) Unblinded (routine clinical care) follow up period: (up to 52 weeks): Subjects will be offered routine clinical care management for their chronic cough
Treatment Arm 5:
Blinded Period 1 (1st 4 weeks): 30mg of Placebo Blinded Period 2 (2nd 4 weeks): 60mg of Placebo (2 pills of 30mg each) Unblinded (routine clinical care) follow up period: (up to 52 weeks): Subjects will be offered routine clinical care management for their chronic cough
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 25
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Duloxetine dose escalation Duloxetine 30 MG 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). Placebo Placebo 30 MG 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). Duloxetine and Placebo Duloxetine 30 MG 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 weeks treatment period). After this, subjects will be unblinded and receive routine clinical care for follow up phase (up to 52 weeks). Duloxetine and Placebo Placebo 30 MG 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 weeks treatment period). After this, subjects will be unblinded and receive routine clinical care for follow up phase (up to 52 weeks). Duloxetine dose escalation Duloxetine 60 MG 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). Amitriptyline dose escalation Amitriptyline 25 MG 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). Amitriptyline and Placebo Amitriptyline 25 MG 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 weeks treatment period). After this, subjects will be unblinded and receive routine clinical care for follow up phase (up to 52 weeks). Amitriptyline dose escalation Amitriptyline 50 MG 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). Placebo Placebo 60 MG 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). Amitriptyline and Placebo Placebo 30 MG 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 weeks treatment period). After this, subjects will be unblinded and receive routine clinical care for follow up phase (up to 52 weeks).
- Primary Outcome Measures
Name Time Method Change in awake objective cough frequency (at 4 & 8 weeks) 4 weeks, 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.
- Secondary Outcome Measures
Name Time Method Change from Baseline in Leicester Cough Questionnaire (LCQ-acute) individual domain and total scores 4 weeks, 8 weeks The Leicester Cough Questionnaire (Acute) is a validated tool for the assessment of chronic cough. It evaluates physical, psychological and social domains and how they are impacted by chronic cough. The physical domain consists of 8 questions, the psychological domain consists of 7 questions, and the social domain consists of 4 questions. The domain score will be calculated as the total score from questions in the domain divided by the number of items in the domain (range 1-7). The total score is the sum of individual domain scores and ranges from 3-21. The individual domain as well as the total score will be reported on weeks 4 \& 8. 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.
Change in Cough Severity Visual Analogue Scale (VAS) 4 weeks, 8 weeks Scored on a 100 mm visual analogue scale at Screening/ Baseline visit (Day -14 to Day 0), and on Days 28, and 56. 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.
Change in 24-Hour cough frequency 4 weeks, 8 weeks This will also be evaluated using using the Leicester Cough Monitor and recordings will be analyzed using the Leicester Cough Monitor program V2.3-MB. All recordings will be kept confidential on a secure encrypted device. 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.
Change in Cough Severity Diary score 4 weeks, 8 weeks Measured using self-reported Cough Severity Diary that patients will fill at baseline and on daily basis. Change in self-reported Cough Severity Diary score at 4 and 8 weeks will be evaluated.
Patients will be asked a series of 6 questions including and will provide an answer using a 5-point Likert scale (never, rarely, sometimes, often, constantly). The following questions will be evaluated:
In the past 24 hours, how often did you cough? In the past 24 hours, how often did you experience coughing fits? In the past 24 hours, how severe was your cough? In the past 24 hours, how often did you have an urge to cough? In the past 24 hours, how often could you control your cough? In the past 24 hours, how severe was your pain from coughing?
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
Trial Locations
- Locations (1)
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States