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Chronic Obstructive Pulmonary DiseasePhase 4NCT02845752

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

A Phase 4 study testing Stiolto Respimat in people with Chronic Obstructive Pulmonary Disease, run by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 45 to 90 years
Conditions the study is for
Chronic Obstructive Pulmonary Disease
What is being tested?
Stiolto Respimat
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
14 participants
Where
1 siteUnited States
Study dates
1 Mar 2017to 6 Aug 2018
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 25Show fewer
  • 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.
  • Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy during clinic visits.
  • Patients who desaturate to SpO2 <85% on screening incremental exercise testing.
  • Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit or patients who are currently in a pulmonary rehabilitation program.
  • Patients who have a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnea, such as arthritis in the leg, angina pectoris or claudication or morbid obesity.
  • Patients with a constant power cycle ergometry endurance time less than 4 or greater than 10 minutes after work rate adjustment procedures (described below).
  • Patients who have taken an investigational drug within one month or six half-lives (whichever is greater) prior to screening visit (Visit 1).
  • Pregnant or nursing women.
  • Women of childbearing who have the potential not to be using a highly effective method of birth control. Female patients will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years.
  • Patients who are currently participating in another interventional study.
  • Patients who are unable to comply with pulmonary medication restrictions prior to randomization.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

    Torrance, California, 90502

Other trials in United States

About this study

Official title: A Randomized, Crossover, Placebo Controlled, Double-blind Trial of the Effect of STIOLTO™ RESPIMAT® on Central and Peripheral Components of Fatigue During Exercise in Chronic Obstructive Pulmonary Disease

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.

Read the detailed description

Patients with chronic obstructive pulmonary disease (COPD) have reduced exercise tolerance. One mechanism for this is thought to be due to dynamic hyperinflation during exercise (an increase in the end-expiratory lung volume) that contributes to the sensation of breathlessness. Whether this also contributes to inhibiting motor recruitment, and reduces the available power output (termed performance fatigue; PF), is not well understood. Preliminary data suggests that many COPD patients, unlike healthy subjects, stop exercise with a 'skeletal muscle power reserve' i.e. the ability to acutely increase muscle power output. This suggests that they are limited in the exercise task by mechanisms other than acute intramuscular limitations to power production (termed muscle fatigue; MF). Exercise tolerance is increased by treatment with the fixed-dose combination bronchodilator, STIOLTO™ RESPIMAT®. We hypothesize that increased exercise tolerance with STIOLTO™ RESPIMAT® (reduced performance fatigue; PF) will be mediated by a combination of: 1) reduced inhibition of muscle activation (termed activation fatigue; AF) allowing patients to drive their leg muscles harder, and thus; 2) increased muscle fatigue (MF).

Being tested
Stiolto Respimat, Placebo Respimat
Medical subject headings
Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Stiolto RespimatDrug

    Also called Tiotropium Bromide and Olodaterol

    Oral inhalation spray

  • Placebo RespimatDrug

    Oral inhalation spray

Study groups in NCT02845752
Study groupRoleWhat they receive
Stiolto RespimatActive comparatorTwo 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.
Receives: Drug: Stiolto Respimat; Drug: Placebo Respimat
Placebo RespimatPlacebo comparatorTwo 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.
Receives: Drug: Stiolto Respimat; Drug: Placebo Respimat

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Baseline and day 7 of each treatment period

Secondary outcomes (13)
  1. 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)

    Constant work rate (CWR) exercise causes fatigue and reduces muscle activation. The relationship between muscle activation and power is measured at baseline (unfatigued condition). 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 fraction of fatigue that is ascribed to reduced muscle activity is then calculated. The magnitude of activation fatigue is measured in EMG activity and expressed in watts at the time of the shortest exercise duration in either study arm, which is termed "isotime". A smaller value (in watts) of activation fatigue means that the intervention was associated with a less reduction in EMG activity after a given CWR exercise duration (i.e. at isotime).

    Measured: Baseline and day 7 of each treatment period

  2. Exercise Endurance Time During CWR Cycling Exercise

    The duration in seconds for which constant work rate (CWR) cycling exercise could be tolerated prior to voluntary termination of exercise.

    Measured: Baseline and day 7 of each treatment period

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

    Inspiratory reserve volume (IRV) measured during CWR cycling exercise at the time of the shortest duration of each intervention arm (isotime). A greater IRV would reflect a beneficial response to intervention.

    Measured: Baseline and day 7 of each treatment period

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

    Inspiratory capacity (IC) measured during constant work rate (CWR) cycling exercise at the time of the shortest duration of each intervention arm (isotime). A greater IC would reflect a beneficial response to the intervention.

    Measured: Baseline and day 7 of each treatment period

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

    This outcome describes the the effect of the intervention on forced expiratory volume in 1 second (FEV1) during resting spirometry. A greater FEV1 would reflect a positive benefit of the intervention.

    Measured: Baseline and day 7 of each treatment period

  6. Change From Period Baseline in the Exercise-isotime in Pulse Oximeter Oxygen Saturation During CWR

    Percentage of arterial hemoglobin that is saturated with oxygen, measured using pulse oximetry during constant work rate (CWR) cycling exercise at the time of the shortest duration of each intervention arm (isotime). A greater pulse oximeter oxygen saturation would reflect a beneficial response to the intervention.

    Measured: Baseline and day 7 of each treatment period

  7. Change From Period Baseline in the Exercise-isotime Ventilation During CWR

    Minute ventilation (VE) measured during constant work rate (CWR) cycling exercise at the time of the shortest duration of each intervention arm (isotime). A lesser VE would reflect a beneficial response to the intervention.

    Measured: Baseline and day 7 of each treatment period

  8. Change From Period Baseline in the Exercise-isotime Oxygen Uptake (VO2) During CWR

    Pulmonary oxygen uptake (VO2) measured during constant work rate (CWR) cycling exercise at the time of the shortest duration of each intervention arm (isotime). A lesser VO2 would reflect a beneficial response to the intervention.

    Measured: Baseline and day 7 of each treatment period

  9. Change From Period Baseline in the Exercise-isotime Frontal Lobe Oxygen Saturation During CWR

    Tissue saturation of hemoglobin with oxygen is measured by spatially resolved near-infrared spectroscopy from the frontal lobe during constant work rate (CWR) cycling exercise at the time of the shortest duration of each intervention arm (isotime). A greater frontal lobe oxygen saturation at isotime would reflect a beneficial response to the intervention.

    Measured: Baseline and day 7 of each treatment period

  10. Change From Period Baseline in the Exercise-isotime Muscle Oxygen Saturation During CWR

    Tissue saturation of hemoglobin plus myoglobin with oxygen is measured by spatially resolved near-infrared spectroscopy from the vastus lateralis muscle during constant work rate (CWR) cycling exercise at the time of the shortest duration of each intervention arm (isotime). A greater muscle oxygen saturation at isotime would reflect a beneficial response to the intervention.

    Measured: Baseline and day 7 of each treatment period

  11. Change From Period Baseline in the Exercise-isotime Borg CR-10 Rating of Perceived Dyspnea During CWR

    Borg rating of perceived shortness of breath (dyspnea) were measured on a category-ratio scale from 0 to 10 (CR-10) during constant work rate (CWR) cycling exercise at the time of the shortest duration of each intervention arm (isotime). A lower CR-10 score for dyspnea at isotime would reflect a beneficial response to the intervention.

    Measured: Baseline and day 7 of each treatment period

  12. Change From Period Baseline in the Exercise-isotime Borg CR-10 Rating of Perceived Leg Fatigue During CWR

    Borg rating of perceived tiredness on the legs (leg fatigue) were measured on a category-ratio scale from 0 to 10 (CR-10) during constant work rate (CWR) cycling exercise at the time of the shortest duration of each intervention arm (isotime). A lower CR-10 score for leg fatigue at isotime would reflect a beneficial response to the intervention.

    Measured: Baseline and day 7 of each treatment period

  13. Change From Period Baseline in the Pre/Post Exercise-induced Decline in Peak Isokinetic Power Normalized to the Measured Muscle Activity (Muscle Fatigue, MF) During CWR

    Constant work rate (CWR) exercise causes muscle fatigue (MF) and reduces muscle activation (activation fatigue; AF). The relationship between muscle activity (using EMG) and power is measured at baseline (unfatigued condition). 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 fraction of the total fall in voluntary isokinetic power (total fatigue) that is ascribed to reduced muscle activity is then calculated from the reduction in EMG activity. The remainder is ascribed to muscle fatigue (MF) and expressed as a percentage of total fatigue. This measurement was made at peak exercise. A smaller value (%) of MF would be associated with a beneficial response to the intervention.

    Measured: Baseline and day 7 of each treatment period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jul 2016 (estimated)
  2. Study start1 Mar 2017
  3. Primary completion6 Aug 2018
  4. Study completion6 Aug 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02845752
Sponsor's protocol ID
1237.55
Other IDs
21394-01
Status last verified
Aug 2020
First submitted
24 Jul 2016
Last updated
6 Aug 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 35323052

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Stiolto Respimat in people with Chronic Obstructive Pulmonary Disease, run by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: Baseline and day 7 of each treatment period). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02845752, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2020.

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