Efficacy of Two Doses of Duloxetine and Amitriptyline in Subjects With Refractory Chronic Cough
ConditionRefractory Chronic Cough
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorMayo Clinic
About this trial
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)
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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%.
Trial design
Design model
Parallel
Treatments tested in this trial
Duloxetine 30 MG
Drug30mg orally for 4 weeks
Duloxetine 60 MG
Drug60mg orally for 4 weeks
Amitriptyline 25 MG
Drug25 mg orally for 4 weeks
Amitriptyline 50 MG
Drug50 mg orally for 4 weeks
Placebo 30 MG
Drug30mg tablet with no active study ingredient for 4 weeks
Placebo 60 MG
Drug60mg tablet with no active study ingredient for 4 weeks
Treatment groups
50 Participants
are divided into 5 treatment groupsGroup A: Duloxetine and PlaceboExperimental treatment 2 interventions
Group B: Duloxetine dose escalationExperimental treatment 2 interventions
Group C: Amitriptyline and PlaceboExperimental treatment 2 interventions
Group D: Amitriptyline dose escalationExperimental treatment 2 interventions
Group E: PlaceboPlacebo comparator 2 interventions
Trial outcomes
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.
Time frame
4 weeks, 8 weeksSecondary outcomes
1
Change in 24-Hour cough frequency
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.
Time frame
4 weeks, 8 weeks2
Change in Cough Severity Diary score
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: 1. In the past 24 hours, how often did you cough? 2. In the past 24 hours, how often did you experience coughing fits? 3. In the past 24 hours, how severe was your cough? 4. In the past 24 hours, how often did you have an urge to cough? 5. In the past 24 hours, how often could you control your cough? 6. 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.
Time frame
4 weeks, 8 weeks3
Change from Baseline in Leicester Cough Questionnaire (LCQ-acute) individual domain and total scores
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.
Time frame
4 weeks, 8 weeks4
Change in Cough Severity Visual Analogue Scale (VAS)
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.
Time frame
4 weeks, 8 weeksSponsors and contacts
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Source ClinicalTrials.gov