Treatment of Chronic Cough in Idiopathic Pulmonary Fibrosis With Thalidomide

Idiopathic Pulmonary Fibrosis (IPF) is a rapidly progressive lung disorder that is often associated with a chronic, intractable cough. The etiology of the cough associated with IPF is unclear but it is often so severe that it adversely effects the patient's quality of life. We propose that thalidomide specifically suppresses the cough associated with idiopathic pulmonary fibrosis via its anti-inflammatory properties, by suppressing the excessive functional up-regulation of sensory fibers with in the respiratory tract of patients with IPF.

This study is a Phase III, double blinded, randomized, placebo controlled, crossover trial testing the efficacy of thalidomide in suppressing the chronic cough of IPF. The primary objective of this study is to determine the efficacy of thalidomide administered daily for 12 weeks to suppress the chronic cough in patients with idiopathic pulmonary fibrosis as measured by cough specific questionnaires, scales and improved quality of life.

Study Overview

• Status: Completed
• Conditions: Cough; Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Thalidomide; Drug: Placebo

Detailed Description

This study is a Phase III, double blinded, randomized, placebo controlled, crossover trial testing the efficacy of thalidomide in suppressing the chronic cough of IPF. All subjects will be randomized to either begin the study receiving the active study drug - (thalidomide) or inactive drug (placebo). Study drug will be administered in escalating dose starting at 50 mg a day increasing to 100 mg a day if cough is still present after 2 weeks. Study drug will be taken by mouth at bedtime. Patients will remain on their initial treatment for 12 weeks. After 12 weeks of treatment, the subjects will be administered the Cough Specific Quality of Life Questionnaire (CQLQ), a visual cough analogue scale, and St. Georges Respiratory Questionnaire (SGRQ). In addition, investigators will collect the subjects cough diary. After 12 weeks of treatment all subjects will enter a 2 week wash-out phase in which all drugs will be discontinued. After the 2 week wash-out phase, all subjects will again be administered the Cough Specific Quality of Life Questionnaire (CQLQ), a visual cough analogue scale, and St. Georges Respiratory Questionnaire (SGRQ). In addition, investigators will collect the subjects cough diary. All subjects will then be crossed over to the other treatment arm for an additional 12 weeks of treatment. After the second 12 weeks of treatment, the subjects will be administered the Cough Specific Quality of Life Questionnaire (CQLQ), a visual cough analogue scale, and St. Georges Respiratory Questionnaire (SGRQ). In addition, investigators will collect the subjects cough diary.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Idiopathic pulmonary fibrosis for >3 months <5 years
• High resolution CT scan of chest consistent with IPF within the previous 12 months
• FVC > 40% and < 90% predicted, TLC >40% <80%, DLCo >30% <90%
• Chronic Cough - cough >8 weeks
• Age >50
• Non-child bearing potential

Exclusion Criteria:

• Pregnant or lactating women
• Women of child bearing potential
• Known etiology of lung fibrosis other than IPF
• Significant respiratory toxin exposure
• Collagen Vascular Disease
• Use of narcotic anti-cough agent in last week
• significant peripheral vascular disease or neuropathy
• history of seizures
• poorly controlled diabetes
• allergy to thalidomide

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental: Thalidomide, then placebo; Participants first received Thalidomide tablet for 12 weeks. After a washout period of two weeks, they then received placebo tablet for 12 weeks.	Drug: Thalidomide; Thalidomide 50 - 100 mg by mouth daily; Drug: Placebo; Placebo 50-100 mg by mouth per day
EXPERIMENTAL: Experimental: Placebo, then Thalidomide; Participants first received Placebo tablet for 12 weeks. After a washout period of two weeks, they then received Thalidomide tablet for 12 weeks.	Drug: Thalidomide; Thalidomide 50 - 100 mg by mouth daily; Drug: Placebo; Placebo 50-100 mg by mouth per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Cough Quality of Life Questionnaire.	The primary endpoint, suppression of cough was measured by the Cough Quality of Life Questionnaire (CQLQ) to measure the effect of interventions on cough-specific quality of life. CQLQ consist of 28 questions about cough and its effects using Likert-like 4-point scales, with lower scores indicating less effect of cough on health related quality of life. CQLQ scale ranges from 28 to 112 ( The lower the value, the higher the quality of life, 28 is considered the best).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Visual Analog Scale of Cough and the St. George Respiratory Questionnaire.	The secondary endpoint, suppression of cough was measured by the visual analog scale of cough (VAS) was significantly lower during treatment with thalidomide than placebo. Secondary endpoints were Cough VAS - the visual analog scale of cough evaluates the severity of cough in patients with IPF. Visual analog scale of cough ranges from 0 to 100 (0 is considered the best). St. George Respiratory Questionnaire helps to evaluate cough-specific and respiratory quality of life in patients with IPF. St. George Respiratory Questionnaire score ranges from 0 to 100 (0 is considered the best).	6 months

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Maureen Horton, MD, Johns Hopkins University

Publications and helpful links

General Publications

• Horton MR, Santopietro V, Mathew L, Horton KM, Polito AJ, Liu MC, Danoff SK, Lechtzin N. Thalidomide for the treatment of cough in idiopathic pulmonary fibrosis: a randomized trial. Ann Intern Med. 2012 Sep 18;157(6):398-406. doi: 10.7326/0003-4819-157-6-201209180-00003.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (ACTUAL): September 1, 2011
• Study Completion (ACTUAL): September 1, 2011

Study Registration Dates

• First Submitted: January 11, 2008
• First Submitted That Met QC Criteria: January 23, 2008
• First Posted (ESTIMATE): January 24, 2008

Study Record Updates

• Last Update Posted (ACTUAL): May 15, 2017
• Last Update Submitted That Met QC Criteria: April 6, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: idiopathic pulmonary fibrosis cough
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Signs and Symptoms, Respiratory; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Cough; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Thalidomide
• Other Study ID Numbers: CG-0747 (OTHER_GRANT: Celgene)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No