Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 21394-01 | Other Identifier | Los Angeles Biomedical Research Institute |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Boehringer Ingelheim | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
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.
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).
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Stiolto Respimat | Drug | Oral inhalation spray |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
Not provided
Inclusion Criteria:
Exclusion Criteria:
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:
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Richard Casaburi, PhD, MD | LABioMed at Harbor-UCLA Medical Center | Principal Investigator |
| Harry Rossiter, PhD | LABioMed at Harbor-UCLA Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center | Torrance | California | 90502 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35323052 | Derived | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Stiolto Respimat, Then Placebo Respimat | Participants first received Stiolto Respimat inhaler (two actuations, once daily for 7 days). After a washout period of 14 days, participants will then received Placebo Respimat inhaler (two actuations, once daily for 7 days). |
| FG001 | Placebo Respimat, Then Stiolto Respimat | Participants first received Placebo Respimat inhaler (two actuations, once daily for 7 days). After a washout period of 14 days, participants will then received Stiolto Respimat inhaler (two actuations, once daily for 7 days). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (7 Days) |
| |||||||||||||
| Washout (14 Days) |
| |||||||||||||
| Second Intervention (7 Days) |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Stiolto Respimat, Then Placebo Respimat | Participants first received Stiolto Respimat inhaler (two actuations, once daily for 7 days). After a washout period of 14 days, participants will then received Placebo Respimat inhaler (two actuations, once daily for 7 days). |
| BG001 | Placebo Respimat, Then Stiolto Respimat |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Posted | Median | Inter-Quartile Range | watts | Baseline and day 7 of each treatment period |
|
8 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Stiolto Respimat | Stiolto Respimat inhaler (two actuations, taken once daily for 7 days). |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Harry Rossiter | The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center | 3102228200 | hrossiter@lundquist.org |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 13, 2015 | Mar 11, 2020 | Prot_SAP_000.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
Not provided
Not provided
| ID | Term |
|---|---|
| C000611386 | tiotropium-olodaterol |
| D000069447 | Tiotropium Bromide |
| C549647 | olodaterol |
| ID | Term |
|---|---|
| D012602 | Scopolamine Derivatives |
| D014326 | Tropanes |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo Respimat | Drug | Oral inhalation spray |
|
| Baseline and day 7 of each treatment period |
| 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. | Baseline and day 7 of each treatment period |
| 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. | Baseline and day 7 of each treatment period |
| 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. | Baseline and day 7 of each treatment period |
| 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. | Baseline and day 7 of each treatment period |
| 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. | Baseline and day 7 of each treatment period |
| 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. | Baseline and day 7 of each treatment period |
| 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. | Baseline and day 7 of each treatment period |
| 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. | Baseline and day 7 of each treatment period |
| 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. | Baseline and day 7 of each treatment period |
| 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. | Baseline and day 7 of each treatment period |
| 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. | Baseline and day 7 of each treatment period |
| 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. | Baseline and day 7 of each treatment period |
| NOT COMPLETED |
|
| NOT COMPLETED |
|
Participants first received Placebo Respimat inhaler (two actuations, once daily for 7 days). After a washout period of 14 days, participants will then received Stiolto Respimat inhaler (two actuations, once daily for 7 days). |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo Respimat | Placebo Respimat inhaler (two actuations, taken once daily for 7 days). |
|
|
| Secondary | 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). | Posted | Median | Inter-Quartile Range | watts | Baseline and day 7 of each treatment period |
|
|
|
| Secondary | 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. | Posted | Median | Inter-Quartile Range | seconds | Baseline and day 7 of each treatment period |
|
|
|
| Secondary | 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. | Posted | Median | Inter-Quartile Range | Liters | Baseline and day 7 of each treatment period |
|
|
|
| Secondary | 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. | Posted | Median | Inter-Quartile Range | Liters | Baseline and day 7 of each treatment period |
|
|
|
| Secondary | 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. | Posted | Median | Inter-Quartile Range | Liters | Baseline and day 7 of each treatment period |
|
|
|
| Secondary | 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. | Posted | Median | Inter-Quartile Range | percent of hemoglobin saturated with O2 | Baseline and day 7 of each treatment period |
|
|
|
| Secondary | 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. | Posted | Median | Inter-Quartile Range | Liters/minute | Baseline and day 7 of each treatment period |
|
|
|
| Secondary | 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. | Posted | Median | Inter-Quartile Range | Liters/minute | Baseline and day 7 of each treatment period |
|
|
|
| Secondary | 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. | Posted | Median | Inter-Quartile Range | Percent of hemoglobin saturated with O2 | Baseline and day 7 of each treatment period |
|
|
|
| Secondary | 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. | Posted | Median | Inter-Quartile Range | % of O2 saturated hemoglobin+myoglobin | Baseline and day 7 of each treatment period |
|
|
|
| Secondary | 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. | Posted | Median | Inter-Quartile Range | scores on a scale | Baseline and day 7 of each treatment period |
|
|
|
| Secondary | 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. | Posted | Median | Inter-Quartile Range | scores on a scale | Baseline and day 7 of each treatment period |
|
|
|
| Secondary | 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. | Posted | Median | Inter-Quartile Range | percentage of total fatigue | Baseline and day 7 of each treatment period |
|
|
|
| 0 |
| 14 |
| 0 |
| 14 |
| 0 |
| 14 |
| EG001 | Placebo Respimat | Placebo Respimat inhaler (two actuations, taken once daily for 7 days). | 0 | 14 | 0 | 14 | 0 | 14 |
Not provided
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009930 |
| Organic Chemicals |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |