What is the mechanism of action of this treatment?

Amitriptyline, a tricyclic antidepressant, and Duloxetine, a serotonin-norepinephrine reuptake inhibitor (SNRI), are common treatments for Chronic Cough. Amitriptyline works by inhibiting the reuptake of norepinephrine and serotonin, increasing their levels in the brain, which helps modulate pain and cough reflexes. Duloxetine similarly increases these neurotransmitters' levels, reducing the sensitivity of the cough reflex. These mechanisms are important for Chronic Cough patients as they target the neural pathways involved in chronic cough, offering potential relief when other treatments have not been effective.

What side effects are associated with this type of intervention?

Amitriptyline and Duloxetine, both used in the treatment of chronic cough, have several known side effects. Common side effects of Amitriptyline include dry mouth, constipation, urinary retention, blurred vision, weight gain, and drowsiness. Duloxetine's side effects often include nausea, dry mouth, constipation, headache, somnolence, dizziness, and insomnia. Both medications can also lower the seizure threshold and should be used cautiously in patients with central nervous system diseases.

What prior FDA approvals exist?

Currently, there are no specific FDA-approved medications for the treatment of chronic cough that directly align with the mechanisms of action of Amitriptyline (a tricyclic antidepressant) and Duloxetine (an SNRI). However, these medications are being studied for their potential efficacy in treating refractory chronic cough due to their ability to modulate neurotransmitters involved in cough reflex pathways. Amitriptyline and Duloxetine, by inhibiting the reuptake of norepinephrine and serotonin, may help reduce cough frequency and severity in patients with chronic cough.

What other types of research exist?

Promising novel alternatives to Amitriptyline and Duloxetine for chronic cough patients include Gabapentin and Pregabalin. Both medications have shown potential in treating chronic cough by modulating neural pathways involved in cough reflex sensitivity. Additionally, Lamotrigine is another alternative that has been effective in some cases of refractory chronic cough.

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Tricyclic Antidepressant

Duloxetine and Amitriptyline for Refractory Chronic Cough (MACS-1 Trial)

Phase 2

Recruiting

Led By Vivek N Iyer, MD

Research Sponsored by Mayo Clinic

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 4 weeks, 8 weeks

Awards & highlights

Approved for 20 Other Conditions

All Individual Drugs Already Approved

Summary

This trial is testing whether Amitriptyline and Duloxetine can help people who have a chronic cough that hasn't improved with other treatments. These medications are usually used for depression and anxiety but might also reduce coughing by changing how the brain processes signals. The study involves different doses to see which works best. Amitriptyline is an antidepressant used for various neurological conditions, including chronic cough, while Duloxetine is known for its efficacy in treating pain and anxiety symptoms.

Who is the study for?

This trial is for adults with a persistent cough lasting over a year, not explained by other lung conditions. Participants must use two forms of birth control and cannot be pregnant or breastfeeding. They should not have severe liver issues, recent infections, or be on certain medications like SSRIs, SNRIs, MAO inhibitors, or specific cough treatments.

What is being tested?

The study tests whether different doses of Duloxetine (30 MG & 60 MG) and Amitriptyline (25 MG & 50 MG), compared to placebos (30 MG & 60 MG), can reduce the frequency of chronic cough in patients who haven't responded to usual treatments.

What are the potential side effects?

Duloxetine and Amitriptyline may cause dry mouth, drowsiness, constipation, blurred vision and weight gain. Some people might experience mood changes or difficulty urinating. Side effects vary from person to person.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 4 weeks, 8 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~4 weeks, 8 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 4 weeks, 8 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

Secondary study objectives

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

Change in 24-Hour cough frequency

Change in Cough Severity Diary score

+1 more

Awards & Highlights

Approved for 20 Other Conditions

This treatment demonstrated efficacy for 20 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

5Treatment groups

Experimental Treatment

Placebo Group

Group I: Duloxetine dose escalationExperimental Treatment2 Interventions

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).

Group II: Duloxetine and PlaceboExperimental Treatment2 Interventions

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).

Group III: Amitriptyline dose escalationExperimental Treatment2 Interventions

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).

Group IV: Amitriptyline and PlaceboExperimental Treatment2 Interventions

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).

Group V: PlaceboPlacebo Group2 Interventions

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).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Duloxetine

FDA approved

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Amitriptyline, a tricyclic antidepressant, and Duloxetine, a serotonin-norepinephrine reuptake inhibitor (SNRI), are common treatments for Chronic Cough. Amitriptyline works by inhibiting the reuptake of norepinephrine and serotonin, increasing their levels in the brain, which helps modulate pain and cough reflexes. Duloxetine similarly increases these neurotransmitters' levels, reducing the sensitivity of the cough reflex. These mechanisms are important for Chronic Cough patients as they target the neural pathways involved in chronic cough, offering potential relief when other treatments have not been effective.

Bulimia nervosa : a review of therapy research.