The Effect of STIOLTO™ RESPIMAT® on Fatigue in Chronic Obstructive Pulmonary Disease

NCT02845752 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: 1237.5521394-01
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether exercise can be prolonged in COPD can by the inhaled bronchodilator Stiolto Respimat. The study will identify whether any endurance benefit is due to reduction in fatigue that originates within the skeletal muscles and/or from effects on neural activation of the skeletal muscles.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• The Magnitude of Change in Isokinetic Power (Performance Fatigue, PF) Associated With Stiolto Respimat Compared With Placebo Respimat at Isotime During Constant Work Rate Exercise (CWR)

  Constant work rate (CWR) exercise causes fatigue. Fatigue is measured by the difference between pre-CWR and post-CWR maximal voluntary isokinetic power i.e. how much maximal voluntary isokinetic power declines during CWR. The magnitude of fatigue is measured in watts at the time of the shortest exercise duration in either study arm, which is termed "isotime". A smaller value (in watts) of performance fatigue means that the intervention was associated with less fatigue after a given CWR exercise duration (i.e. at isotime).

  Baseline and day 7 of each treatment period

Secondary Outcomes (13)

• The Magnitude of Change Electromyographic (EMG) Muscle Activity (Activation Fatigue, AF) Associated With Stiolto Respimat Compared With Placebo Respimat at Isotime During Constant Work Rate Exercise (CWR)

  Baseline and day 7 of each treatment period

• Exercise Endurance Time During CWR Cycling Exercise

  Baseline and day 7 of each treatment period

• Change From Period Baseline in the Exercise-isotime Inspiratory Reserve Volume During CWR

  Baseline and day 7 of each treatment period

• Change From Period Baseline in the Exercise-isotime Inspiratory Capacity During CWR

  Baseline and day 7 of each treatment period

• Change From Period Baseline in the Forced Expiratory Volume in 1 Second (FEV1)

  Baseline and day 7 of each treatment period

Study Arms (2)

Stiolto Respimat

ACTIVE COMPARATOR

Two actuations of Stiolto Respimat inhaler, taken once daily for 7 days. After a washout period of 14 days, participants will then receive matching Placebo for 7 days.

Drug: Stiolto Respimat; Drug: Placebo Respimat

Placebo Respimat

PLACEBO COMPARATOR

Two actuations of Placebo Respimat inhaler, taken once daily for 7 days. After a washout period of 14 days, participants will then receive matching Placebo for 7 days.

Drug: Stiolto Respimat; Drug: Placebo Respimat

Interventions

Stiolto Respimat DRUG

Oral inhalation spray

Also known as: Tiotropium Bromide and Olodaterol

Placebo Respimat; Stiolto Respimat

Placebo Respimat DRUG

Oral inhalation spray

Placebo Respimat; Stiolto Respimat

Eligibility Criteria

• Age: 45 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following criteria: (a) Patients must be in a stable state of their disease with no exacerbation within the previous 4 weeks; and (b) At visit 1 spirometric must demonstrate a post-bronchodilator FEV1 \<80% of predicted normal and a post-bronchodilator FEV1/FVC \<70%.
• At visit 1, patients will demonstrate appreciable reversibility, defined as a 12% increase in FEV1 in response to albuterol administration.
• Baseline dyspnea index focal score ≤ 9.
• Male or female patients, between 45 and 90 years (inclusive) of age.
• Patients must be current or ex-smokers with a smoking history of more than 10 pack-years
• Patients must be able to perform technically acceptable pulmonary function tests must be able to complete multiple symptom-limited cycle ergometry tests.
• Patients must be able to inhale medication in a competent manner from the inhalers used in the study.

You may not qualify if:

• Patients with a significant disease other than COPD; a significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the study, (ii) influence the results of the study, or (iii) cause concern regarding the patient's ability to participate in the study.
• Patients with a documented history of asthma. For patients with allergic rhinitis or atopy, medical records will be required to verify that the patient does not have asthma.
• Patients with any of the following conditions:
• A history of myocardial infarction within 1 year of screening visit.
• Unstable or life-threatening cardiac arrhythmia.
• Hospitalized for heart failure within the past year.
• Known active tuberculosis.
• A malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last two years (patients with treated basal cell carcinoma are allowed).
• A history of life-threatening pulmonary obstruction within the past two years.
• A history of cystic fibrosis.
• Clinically evident bronchiectasis.
• A history of significant alcohol or drug abuse within the past two years.
• Any contraindications for exercise testing as outlined below (see contraindications to exercise).
• Patients who have undergone thoracotomy with pulmonary resection.
• Patients being treated with oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day.

Sponsors & Collaborators

• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Related Publications (1)

• Cao M, Calmelat RA, Kierstead P, Carraro N, Stringer WW, Porszasz J, Casaburi R, Rossiter HB. A randomized, crossover, placebo controlled, double-blind trial of the effects of tiotropium-olodaterol on neuromuscular performance during exercise in COPD. J Appl Physiol (1985). 2022 May 1;132(5):1145-1153. doi: 10.1152/japplphysiol.00332.2021. Epub 2022 Mar 24.

  PMID: 35323052 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

tiotropium-olodaterol; Tiotropium Bromide; olodaterol

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Dr. Harry Rossiter
• Organization: The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

hrossiter@lundquist.org

3102228200

Study Officials

• Richard Casaburi, PhD, MD

  LABioMed at Harbor-UCLA Medical Center

  PRINCIPAL INVESTIGATOR

• Harry Rossiter, PhD

  LABioMed at Harbor-UCLA Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 24, 2016
• First Posted: July 27, 2016
• Study Start: March 1, 2017
• Primary Completion: August 6, 2018
• Study Completion: August 6, 2018
• Last Updated: August 6, 2020
• Results First Posted: June 16, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)