Refractory Chronic CoughPhase 2MACS-1NCT05110144
Efficacy of Two Doses of Duloxetine and Amitriptyline in Subjects With Refractory Chronic Cough
A Phase 2 study testing Duloxetine 30 MG, Duloxetine 60 MG and Amitriptyline 25 MG in people with Refractory Chronic Cough, run by Mayo Clinic at 1 site in United States.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Refractory Chronic Cough
- What is being tested?
- Duloxetine 30 MG, Duloxetine 60 MG and Amitriptyline 25 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2021to Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
- History of previous hypersensitivity or intolerance to Duloxetine \& Amitriptyline (patients who have previously been on either amitriptyline or duloxetine for chronic cough or other reasons and have tolerated the medication will be offered participation regardless of previous response to therapy).
- Currently pregnant or breastfeeding female subject.
- Presence of any medical condition or disability that the investigators believe could interfere with the assessment of safety or efficacy in this trial or compromise the safety of the subject.
- Planned or anticipated major surgical procedure or other activity that would interfere with the subject's ability to comply with protocol-mandated assessments (e.g., extended travel) during the subject's participation in the study.
- Currently taking either another SSRI, SNRI or MAO inhibitor which the patient cannot safely discontinue at least 2 weeks prior to the screening period.
- The following therapies are prohibited from 2 week prior to the Screening/Baseline Visit (Day -14 to Day 0) through the end of the 8-week blinded treatment period.
- Opioids (of any kind including tramadol \& codeine) specifically prescribed for treatment of cough
- Dextromethorphan
- Guaifenesin
- Chlorpheniramine
- Benzonatate
- Trazodone
- Pregabalin or gabapentin prescribed for chronic cough
- 1% tetracaine lollipops prescribed for chronic cough
- 4% nebulized lidocaine solution prescribed for chronic cough
- Any SSRI (selective serotonin reuptake inhibitor) e.g. bupropion, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine.
- Any SNRI (serotonin-norepinephrine reuptake inhibitor) e.g. venlafaxine, desvenlafaxine, milnacipran, levomilnacipran
- Any Tricyclic antidepressant e.g. doxepin, clomipramine, nortriptyline, imipramine, protriptyline, amoxapine, trimipramine
- Any MAO (Monoamine oxidase) inhibitor. e.g. phenelzine, selegiline, isocarboxacid or tranylcypromine
- Patients who were previously prescribed either amitriptyline or duloxetine for chronic cough will be eligible for the study as long as they had discontinued the medication at least 12 weeks prior to the Screening/Baseline Visit (Day -14 to Day 0).
- The following therapies are prohibited from 4 week prior to the Screening/Baseline Visit (Day -14 to Day 0) through the end of the 8-week blinded treatment period.
- Investigational biologic or pharmaceutical therapies (excluding COVID vaccination and COVID related monoclonal antibody therapy)
- The following therapies are prohibited from 12 week prior to the Screening/Baseline Visit (Day -14 to Day 0) through the end of the 8-week blinded treatment period.
- Treatment with an ACE-inhibitor
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Sue Ann Donlinger, 507-284-9259, Donlinger.SueAnn@mayo.edu
Vivek N Iyer, M.D, M.P.H
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Dose-escalation Study Evaluating the Efficacy of Two Doses of Duloxetine & Amitriptyline in Subjects With Refractory Chronic Cough
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)
Read the detailed description
This is a randomized, double-blind, placebo-controlled, parallel-arm, dose escalation study of Duloxetine \& Amitriptyline in subjects with refractory chronic cough. Subjects will be screened during a period of up to 2 week and will undergo screening/ baseline cough monitoring. 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. 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
- Conditions
- Refractory Chronic Cough
- Being tested
- Duloxetine 30 MG, Duloxetine 60 MG, Amitriptyline 25 MG, Amitriptyline 50 MG, Placebo 30 MG
- Keywords
- Cough, Chronic cough, asthma, GERD, Upper airway cough syndrome, antitussives, cough hypersensitivity, refractory cough, neurogenic cough, Gastroesophageal reflux, Chronic rhinosinusitis, refractory
- Medical subject headings
- Chronic Cough, Cough, Asthma, Gastroesophageal Reflux, upper airway cough syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Duloxetine 30 MGDrug
30mg orally for 4 weeks
Duloxetine 60 MGDrug
60mg orally for 4 weeks
Amitriptyline 25 MGDrug
25 mg orally for 4 weeks
Amitriptyline 50 MGDrug
50 mg orally for 4 weeks
Placebo 30 MGDrug
30mg tablet with no active study ingredient for 4 weeks
Placebo 60 MGDrug
60mg tablet with no active study ingredient for 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: 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). Receives: 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). Receives: 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). Receives: Drug: Placebo 30 MG; Drug: Placebo 60 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 weeks, 8 weeks
Secondary outcomes (4)
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.
Measured: 4 weeks, 8 weeks
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:
- 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.
Measured: 4 weeks, 8 weeks
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.
Measured: 4 weeks, 8 weeks
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.
Measured: 4 weeks, 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2021
- Study start1 Nov 2021
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Chronic CoughStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Vivek N Iyer, Mayo Clinic
- Investigators
- Vivek N Iyer, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05110144
- Sponsor's protocol ID
- 21-008116
- Acronym
- MACS-1
- Status last verified
- Jan 2026
- First submitted
- 3 Nov 2021
- Last updated
- 21 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Dose-escalation Study Evaluating the Efficacy of Two Doses of Duloxetine & Amitriptyline in Subjects With Refractory Chronic Cough
- ClinicalTrials.gov ID
- NCT05110144
- Acronym / sponsor ID
- MACS-1 / 21-008116
- Conditions
- Refractory Chronic Cough
- Keywords
- Cough, Chronic cough, asthma, GERD, Upper airway cough syndrome, antitussives, cough hypersensitivity, refractory cough
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 1 Nov 2021 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 5 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Detailed description
This is a randomized, double-blind, placebo-controlled, parallel-arm, dose escalation study of Duloxetine \& Amitriptyline in subjects with refractory chronic cough. Subjects will be screened during a period of up to 2 week and will undergo screening/ baseline cough monitoring. 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. 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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Duloxetine and Placebo | Experimental | Drug: Duloxetine 30 MG, Drug: Placebo 30 MGSubjects 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). |
| Duloxetine dose escalation | Experimental | Drug: Duloxetine 30 MG, Drug: Duloxetine 60 MGSubjects 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 and Placebo | Experimental | Drug: Amitriptyline 25 MG, Drug: Placebo 30 MGSubjects 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). |
| Amitriptyline dose escalation | Experimental | Drug: Amitriptyline 25 MG, Drug: Amitriptyline 50 MGSubjects 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 comparator | Drug: Placebo 30 MG, Drug: Placebo 60 MGSubjects 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (39 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Duloxetine 30 MG30mg orally for 4 weeks | Drug | Duloxetine and Placebo, Duloxetine dose escalation |
| Duloxetine 60 MG60mg orally for 4 weeks | Drug | Duloxetine dose escalation |
| Amitriptyline 25 MG25 mg orally for 4 weeks | Drug | Amitriptyline and Placebo, Amitriptyline dose escalation |
| Amitriptyline 50 MG50 mg orally for 4 weeks | Drug | Amitriptyline dose escalation |
| Placebo 30 MG30mg tablet with no active study ingredient for 4 weeks | Drug | Amitriptyline and Placebo, Duloxetine and Placebo, Placebo |
| Placebo 60 MG60mg tablet with no active study ingredient for 4 weeks | Drug | Placebo |
Primary outcome
Change in awake objective cough frequency (at 4 & 8 weeks)
Time frame: 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.
4 secondary outcomes
Change in 24-Hour cough frequency
Time frame: 4 weeks, 8 weeks
Change in Cough Severity Diary score
Time frame: 4 weeks, 8 weeks
Change from Baseline in Leicester Cough Questionnaire (LCQ-acute) individual domain and total scores
Time frame: 4 weeks, 8 weeks
Change in Cough Severity Visual Analogue Scale (VAS)
Time frame: 4 weeks, 8 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2026.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Vivek N Iyer, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Duloxetine 30 MG, Duloxetine 60 MG and Amitriptyline 25 MG in people with Refractory Chronic Cough, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in awake objective cough frequency (at 4 & 8 weeks) (time frame: 4 weeks, 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2026.