Trial Outcomes & Findings for The Effects of Tiotropium on the Cough Reflex in Patients With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT00870896)

Results Overview

We measured the change in the number of coughs following capsaicin inhalation challenge from baseline followed by 30 days of treatment with spiriva

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

5 participants

Primary outcome timeframe

30 days

Results posted on

2014-10-01

Participant Flow

10/14/08 to 2/5/09

Unable to recruit 20 participates study stopped at 5

Participant milestones

Participant milestones
Measure	Group 1 Capsaicin Inhalation challenge (CIH): Each solution of capsaicin administered to a subject will be quantified by HPLC. Solutions of capsaicin are prepared to make a stock solution of 0.01 Mol and subsequently further diluted with physiologic saline solution to yield 11 serial doubling concentrations from 0.98 to 1,000 uMol/L. Final diluted capsaicin concentrations are: 0.98, 1.95, 3.9, 7.8, 15.6, 31.2, 62.5, 125, 250, 500, and 1000 uMol/L. Single breaths of capsaicin are delivered in ascending order, with normal saline solution randomly interspersed to increase challenge blindness, until two or more coughs (C2) and five or more coughs (C5) are reached. The different concentrations are delivered at 2 minute intervals. CIH is administered at baseline one and 3 months following treatment with Spiriva
Overall Study STARTED	5
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The Effects of Tiotropium on the Cough Reflex in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tiotropium n=5 Participants Subjects 40-80 with \> 10 pk/year or ex-smoker stopped within 1 year with 10 pk/year smoking history, Subjects with mild and moderate COPD defined by ATS/ERS clinically stable for 4 weeks, subjects off tiotropium or ipratropium 1 month prior to start, Chronic cough Defined by ATS/ERS Exclusion:Age \< 40 or \> 80, Refusal to volunteer, Lung disease other than COPD,O2 or ventilator dependent COPD, Received antibiotics or a change in inhaled steroid during last 4 weeks.History CHF, cardiomyopathy, valvular heart disease, angina, arrhythmia, MI or uncontrolled HTN within last 6 months, History chronic hepatitis/cirrhosis, End-stage renal disease, neurologic or psychiatric disorder, Physician diagnosis GERD/allergic/non-allergic rhinitis/sinusitis/lung cancer/radiation to the chest or mediastinum/Lung volume reduction surgery/lobectomy/pneumonectomy/thoracotomy, Symptomatic BPH/bladder outlet obstruction/glaucoma Severe COPD defined ERS/ATS, Allergic response or history of allergy to lactose
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	56 years STANDARD_DEVIATION 4.52 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants

PRIMARY outcome

Timeframe: 30 days

Population: Power two-sided t-test for C5. our previous studies coefficient of variation for C5 was 3.2%. We propose power 0.80/significance 0.05. multiple comparisons utilize Bonferroni procedure significance will be 0.017 ability to detect minimum difference of 3.7 uMol. Thus, if alpha 0.05 and beta 0.20, to detect difference require 20 subjects each group.

We measured the change in the number of coughs following capsaicin inhalation challenge from baseline followed by 30 days of treatment with spiriva

Outcome measures

Outcome measures
Measure	Group 1 n=5 Participants Capsaicin Inhalation Challenge Testing (CICT) will follow the protocol of Dicpinigaitis et al (Chest 2003; 123:685-8). CICT will be performed at baseline before beginning treatment with tiotropium and at 4 weeks after initiation of treatment. Solutions of capsaicin are prepared to make a stock solution of 0.01 Mol and subsequently further diluted with physiologic saline solution to yield 11 serial doubling concentrations from 0.98 to 1,000 uMol/L. Final diluted capsaicin concentrations are: 0.98, 1.95, 3.9, 7.8, 15.6, 31.2, 62.5, 125, 250, 500, and 1000 uMol/L. Single breaths of capsaicin are delivered in ascending order, with normal saline solution randomly interspersed to increase challenge blindness, until five or more coughs (C5) are reached. We measured the change in the number of coughs at baseline and following 30 days of treatment with spiriva
Number of Coughs Following Capsaicin Inhalation Challenge at Baseline and Following 30 Days of Treatment With Spiriva (Baseline and 30 Days)	2.5 coughs per dose of capsaicin Standard Deviation 2.75

SECONDARY outcome

Timeframe: 30 days

Population: Power two-sided t-test for C5. our previous studies coefficient of variation for C5 was 3.2%. We propose power 0.80/significance 0.05. multiple comparisons utilize Bonferroni procedure significance will be 0.017 ability to detect minimum difference of 3.7 uMol. Thus, if alpha 0.05 and beta 0.20, to detect difference require 20 subjects each group.

Change in FEV1 ( in liters) at baseline and following 30 days of treatment with Spiriva

Outcome measures

Outcome measures
Measure	Group 1 n=5 Participants Capsaicin Inhalation Challenge Testing (CICT) will follow the protocol of Dicpinigaitis et al (Chest 2003; 123:685-8). CICT will be performed at baseline before beginning treatment with tiotropium and at 4 weeks after initiation of treatment. Solutions of capsaicin are prepared to make a stock solution of 0.01 Mol and subsequently further diluted with physiologic saline solution to yield 11 serial doubling concentrations from 0.98 to 1,000 uMol/L. Final diluted capsaicin concentrations are: 0.98, 1.95, 3.9, 7.8, 15.6, 31.2, 62.5, 125, 250, 500, and 1000 uMol/L. Single breaths of capsaicin are delivered in ascending order, with normal saline solution randomly interspersed to increase challenge blindness, until five or more coughs (C5) are reached. We measured the change in the number of coughs at baseline and following 30 days of treatment with spiriva
Change in FEV1 (in Liters)	.315 liters Standard Deviation 138

SECONDARY outcome

Timeframe: 30 days

We measured the change in FEV1/FVC ratio at baseline and following 30 days of treatment with Spiriva.Change in ratio reflects the percentage value (ratio) at 30 days minus the percentage value (ratio) at baseline x 100

Outcome measures

Outcome measures
Measure	Group 1 n=5 Participants Capsaicin Inhalation Challenge Testing (CICT) will follow the protocol of Dicpinigaitis et al (Chest 2003; 123:685-8). CICT will be performed at baseline before beginning treatment with tiotropium and at 4 weeks after initiation of treatment. Solutions of capsaicin are prepared to make a stock solution of 0.01 Mol and subsequently further diluted with physiologic saline solution to yield 11 serial doubling concentrations from 0.98 to 1,000 uMol/L. Final diluted capsaicin concentrations are: 0.98, 1.95, 3.9, 7.8, 15.6, 31.2, 62.5, 125, 250, 500, and 1000 uMol/L. Single breaths of capsaicin are delivered in ascending order, with normal saline solution randomly interspersed to increase challenge blindness, until five or more coughs (C5) are reached. We measured the change in the number of coughs at baseline and following 30 days of treatment with spiriva
Change in FEV1/FVC Ratio	3 percentage change Standard Deviation 5.74

Adverse Events

Tiotropium

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Thomas Truncale

University of South Florida

Phone: 813 974 8952

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place