Treatment of Chronic Cough in Idiopathic Pulmonary Fibrosis With Thalidomide

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00600028
• Collaborator: (none)
• Enrollment: 25
• Location: 1
• Arms: 2
• Duration (Months): 45
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Pulmonary Fibrosis; Cough	Drug: Thalidomide; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Treatment of Chronic Cough in Idiopathic Pulmonary Fibrosis With Thalidomide
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Cough Quality of Life Questionnaire. [6 months]

   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).

Secondary Outcome Measures

1. 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. [6 months]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Bayview Medical Center	Baltimore	Maryland	United States	21224

Sponsors and Collaborators

• Johns Hopkins University

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Maureen R. Horton, Associate Professor of Medicine, Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT00600028
• Other Study ID Numbers: CG-0747; CG-0747
• First Posted: Jan 24, 2008
• Last Update Posted: May 15, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Maureen R. Horton, Associate Professor of Medicine, Johns Hopkins University: idiopathic pulmonary fibrosis cough
• Additional relevant MeSH terms: Pulmonary Fibrosis; Cough; Idiopathic Pulmonary Fibrosis; Fibrosis; Thalidomide

Study Results

Participant Flow

Recruitment Details	Consecutive eligible patients were recruited by the investigators from their clinics and through self-referral between February 2008 and March 2011. 98 persons contacted our study coordinator with queries about the trial, 22 from the Johns Hopkins Interstitial Lung Disease Clinic and 76 in response to the ClinicalTrials.gov Web site.
Pre-assignment Detail	One participant was excluded because of an FVC>90% predicted

Arm/Group Title	Drug Thalidomide First, Then Placebo	Placebo First, Then Thalidomide Drug
Arm/Group Description	Drug Thalidomide 50-100mg daily in the first intervention period and placebo daily in the second intervention period (after washout period)	Placebo was administered in the first interventional period and Thalidomide 50-100mg daily in the second interventional period (after washout period).
Period Title: First Intervention (12 Weeks)
STARTED	13	11
COMPLETED	12	10
NOT COMPLETED	1	1
Period Title: First Intervention (12 Weeks)
STARTED	12	10
COMPLETED	12	8
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Drug Thalidomide First, Then Placebo	Placebo First, Then Thalidomide Drug	Total
Arm/Group Description	Drug thalidomide 50 - 100 mg daily in the first intervention period and placebo daily in the second intervention period (after washout period)	Placebo was administered in the first intervention period and Thalidomide 50 - 100 mg daily in the second intervention period(After washout period)	Total of all reporting groups
Overall Participants	13	11	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	13 100%	11 100%	24 100%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.5 (7.11)	65.55 (7.38)	67.8 (7.8)
Sex: Female, Male (Count of Participants)
Female	5 38.5%	5 45.5%	10 41.7%
Male	8 61.5%	6 54.5%	14 58.3%
Region of Enrollment (participants) [Number]
United States	13 100%	11 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Efficacy of Thalidomide in Suppressing the Chronic Cough of Idiopathic Pulmonary Fibrosis Using the Cough Quality of Life Questionnaire.
Description	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).
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

All participants who received the interventions and completed all study visits were included in the efficacy analysis.

Arm/Group Title	Arm Thalidomide 1st, Placebo 2nd (Intervention Thalidomide)	Arm Thalidomide 1st, Placebo 2nd (Intervention Placebo)	Arm Placebo 1st, Thalidomide 2nd (Intervention Placebo)	Arm Placebo 1st, Thalidomide 2nd (Intervention Thalidomide)
Arm/Group Description	Intervention Thalidomide : thalidomide 50 - 100 mg by mouth daily in the first intervention period	Intervention Placebo : Placebo 50-100 mg by mouth per day in the second intervention period	Intervention Placebo : Placebo 50 - 100 mg by mouth daily in the first intervention period	Intervention Thalidomide : thalidomide 50 - 100 mg by mouth daily in the second intervention period
Measure Participants	12	12	10	8
Mean (Standard Deviation) [units on a scale]	47.3 (13.7)	55.2 (14.4)	61.6 (11.9)	44.5 (12.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm Thalidomide 1st, Placebo 2nd (Intervention Thalidomide), Arm Thalidomide 1st, Placebo 2nd (Intervention Placebo)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The values represents three months on each intervention

2. Secondary Outcome

Title	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.
Description	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).
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

All participants who received the interventions and completed all study visits were included in the efficacy analysis.

Arm/Group Title	Arm Thalidomide 1st, Placebo 2nd (Intervention Thalidomide)	Arm Thalidomide 1st, Placebo 2nd (Intervention Placebo)	Arm Placebo 1st, Thalidomide 2nd (Intervention Placebo)	Arm Placebo 1st, Thalidomide 2nd (Intervention Thalidomide)
Arm/Group Description	Intervention Thalidomide : thalidomide 50 - 100 mg by mouth daily in the first intervention period	Intervention Placebo : Placebo 50-100 mg by mouth per day in the second intervention period	Intervention Placebo : Placebo 50-100 mg by mouth per day in the first intervention period	Intervention Thalidomide : thalidomide 50 - 100 mg by mouth daily in the second intervention period
Measure Participants	12	12	10	8
Severity of cough (VAS Score)	30.3 (28.5)	65.9 (23.3)	68 (26.8)	17.8 (9.9)
Quality of life (SGRQ Score)	46.4 (19.4)	54.7 (16.9)	58.8 (13.3)	40.7 (9.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm Thalidomide 1st, Placebo 2nd (Intervention Thalidomide), Arm Thalidomide 1st, Placebo 2nd (Intervention Placebo)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The values represents three months on each intervention

Adverse Events

Arm/Group Title	Thalidomide		Placebo
Arm/Group Description	Thalidomide : thalidomide 50 - 100 mg by mouth daily		Placebo : Placebo 50-100 mg by mouth per day
All Cause Mortality
	Thalidomide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Thalidomide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Thalidomide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/23 (34.8%)		1/23 (4.3%)
Gastrointestinal disorders
constipation	8/23 (34.8%)	8	1/23 (4.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.