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Efficacy of Two Doses of Duloxetine and Amitriptyline in Subjects With Refractory Chronic Cough (MACS-1)

Primary Purpose

Refractory Chronic Cough

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Duloxetine 30 MG
Duloxetine 60 MG
Amitriptyline 25 MG
Amitriptyline 50 MG
Placebo 30 MG
Placebo 60 MG
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Chronic Cough focused on measuring Cough, Chronic cough, asthma, GERD, Upper airway cough syndrome, antitussives, cough hypersensitivity, refractory cough, neurogenic cough, Gastroesophageal reflux, Chronic rhinosinusitis, refractory

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

  • 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.

Exclusion Criteria

  • 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
  • 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

Sites / Locations

  • Mayo Clinic in RochesterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Duloxetine and Placebo

Duloxetine dose escalation

Amitriptyline and Placebo

Amitriptyline dose escalation

Placebo

Arm Description

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).

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).

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).

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).

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
November 3, 2021
Last Updated
February 10, 2023
Sponsor
Mayo Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT05110144
Brief Title
Efficacy of Two Doses of Duloxetine and Amitriptyline in Subjects With Refractory Chronic Cough
Acronym
MACS-1
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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)
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Duloxetine and Placebo
Arm Type
Experimental
Arm Description
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).
Arm Title
Duloxetine dose escalation
Arm Type
Experimental
Arm Description
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).
Arm Title
Amitriptyline and Placebo
Arm Type
Experimental
Arm Description
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).
Arm Title
Amitriptyline dose escalation
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Duloxetine 30 MG
Intervention Description
30mg orally for 4 weeks
Intervention Type
Drug
Intervention Name(s)
Duloxetine 60 MG
Intervention Description
60mg orally for 4 weeks
Intervention Type
Drug
Intervention Name(s)
Amitriptyline 25 MG
Intervention Description
25 mg orally for 4 weeks
Intervention Type
Drug
Intervention Name(s)
Amitriptyline 50 MG
Intervention Description
50 mg orally for 4 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo 30 MG
Intervention Description
30mg tablet with no active study ingredient for 4 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo 60 MG
Intervention Description
60mg tablet with no active study ingredient for 4 weeks
Primary Outcome Measure Information:
Title
Change in awake objective cough frequency (at 4 & 8 weeks)
Description
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 weeks
Secondary Outcome Measure Information:
Title
Change in 24-Hour cough frequency
Description
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 weeks
Title
Change in Cough Severity Diary score
Description
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.
Time Frame
4 weeks, 8 weeks
Title
Change from Baseline in Leicester Cough Questionnaire (LCQ-acute) individual domain and total scores
Description
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 weeks
Title
Change in Cough Severity Visual Analogue Scale (VAS)
Description
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 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria 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. Exclusion Criteria 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vivek N Iyer, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sue Ann Donlinger
Phone
507-284-9259
Email
Donlinger.SueAnn@mayo.edu
First Name & Middle Initial & Last Name & Degree
Hasan Albitar, M.D
Phone
507-284-2494
Email
MACS@mayo.edu
First Name & Middle Initial & Last Name & Degree
Vivek N Iyer, M.D, M.P.H
First Name & Middle Initial & Last Name & Degree
Hasan A Albitar, M.D
First Name & Middle Initial & Last Name & Degree
Vaibhav Ahluwalia, M.B.B.S
First Name & Middle Initial & Last Name & Degree
Augustine Lee, M.D

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

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

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