What side effects are associated with this type of intervention?

Common side effects of treatments for Interstitial Lung Disease (ILD) similar to Amitriptyline (a tricyclic antidepressant) and Duloxetine (a serotonin-norepinephrine reuptake inhibitor) include dry mouth, constipation, urinary retention, blurred vision, weight gain, and sedation for TCAs, and nausea, dry mouth, constipation, headache, somnolence, dizziness, and insomnia for SNRIs. Both classes of drugs may also lower the seizure threshold and should be used cautiously in patients with central nervous system disease.

What prior FDA approvals exist?

Currently, there are no specific FDA approvals for the use of Amitriptyline or Duloxetine in the treatment of Interstitial Lung Disease (ILD). However, these drugs are being studied for their potential benefits in reducing ILD-related cough due to their properties as serotonin-norepinephrine reuptake inhibitors. The primary FDA-approved treatments for ILD, particularly idiopathic pulmonary fibrosis (a type of ILD), include antifibrotic agents such as nintedanib and pirfenidone, which work by slowing disease progression rather than addressing symptoms like cough.

What other types of research exist?

Promising novel alternatives to Amitriptyline and Duloxetine for ILD patients include Gabapentin and Pregabalin, which are effective for neuropathic pain. Additionally, Lamotrigine is a potential option for patients who do not respond to initial therapies, though it should be used cautiously due to potential side effects. Non-systemic approaches like topical therapies and acupuncture may also be considered as adjunctive treatments.

← Back to Search

Tricyclic Antidepressant

Duloxetine + Amitriptyline for Interstitial Lung Disease-related Cough (MACS-2 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

Summary

This trial is testing whether Amitriptyline and Duloxetine can reduce coughing in people with interstitial lung disease. These medications, usually used for depression and anxiety, might help by changing how the brain processes signals that cause coughing. The study involves different doses of these medications.

Who is the study for?

This trial is for adults with interstitial lung disease who've had a chronic cough for at least 3 months, are on stable ILD treatments, and can follow the study plan. Women must use two birth control methods or practice complete abstinence; men also need to use two forms of contraception. Smokers, those with certain liver issues, pregnant/breastfeeding women, and people on conflicting medications or other trials cannot participate.

What is being tested?

The study tests whether increasing doses of Amitriptyline (25mg or 50mg) and Duloxetine (30mg or 60mg) can reduce coughing in ILD patients compared to placebo. Participants will be randomly assigned to receive one of these drugs or a matching placebo over an eight-week period while continuing their usual ILD therapies.

What are the potential side effects?

Potential side effects include dry mouth, drowsiness, constipation, blurred vision from Amitriptyline; nausea, headache, dry mouth, sleepiness from Duloxetine. Side effects vary by individual and dosage.

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

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 weeks 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 weeks 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 30 MG

2021

Completed Phase 2

~330

Do I qualify?Apply below to find out

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 and Duloxetine are being studied for their potential to reduce cough frequency in Interstitial Lung Disease (ILD) patients. Amitriptyline, a tricyclic antidepressant, inhibits the reuptake of norepinephrine and serotonin, thereby increasing their levels in the brain and modulating pain and mood. Duloxetine, a serotonin-norepinephrine reuptake inhibitor (SNRI), similarly increases these neurotransmitter levels. These mechanisms are important because ILD often involves chronic cough and pain, which can significantly impact quality of life. By modulating neurotransmitter levels, these drugs may offer symptomatic relief, improving overall patient well-being.

The antifibrotic effects of alveolar macrophages 5-HT2C receptors blockade on bleomycin-induced pulmonary fibrosis in rats.Exposure to commonly prescribed drugs and the etiology of cryptogenic fibrosing alveolitis: a case-control study.