Fentanyl Sublingual Spray for Exercise-Induced Breakthrough Dyspnea

Study Overview
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Brief Summary
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The goal of this clinical research study is to learn if fentanyl can help shortness of breath in cancer patients. Researchers also want to learn if the study drug can help to improve your physical function.

Detailed Description
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If you agree to take part in this study, the study staff will collect information from your medical record about your age, sex, race, and disease type, as well as how well you are able to perform the normal activities of daily living, any drugs you are taking, and any possible causes of shortness of breath. Study Groups: You will be randomly assigned (as in the flip of a coin) to receive either low-dose or high-dose fentanyl spray. This is done because no one knows if one study group is better, the same, or worse than the other group. Study Visit: During your study visit, you will complete 2 questionnaires about any breathing problems or other symptoms you may be having. It should take about 10 minutes total to complete these questionnaires. You will blow into a device called a spirometer a few times to measure your lung function. You will also be asked to inhale into another device called a negative inspiratory force meter (NIF). This device measures the volume of air that can be inhaled after normal breathing. The study staff will then record your vital signs (heart rate, breathing rate, blood pressure, and your blood-oxygen level). Your blood-oxygen level will be measured with a device that will be clipped gently onto your fingertip). You will then be asked how hard it is to catch your breath and to rate your level of tiredness. When instructed, you will walk back and forth between 2 cones in an indoor hallway for up to 12 minutes. This is called the Shuttle Walk Test. The purpose of this timed test is to see how far and fast you can walk without stopping for a rest. You will be asked to pivot briskly around the cones and continue back the other way. You may stop this test at any time if you feel you cannot continue. After that, you will sit down and rest for up to 1 hour. During this time, the study drug will be prepared, and you may be asked at different times how hard it is to catch your breath. After the rest period, you will be given the fentanyl to spray into your mouth and under your tongue. About 10 minutes later, you will be asked about any side effects you may be having. At that point, you will perform a second Shuttle Walk Test. Then the study staff will ask you again about any side effects you may be having, your level of tiredness, and how hard it is to catch your breath. Your vital signs will also be measured. The total distance you walked will also be recorded. After each walk test, you will also be asked to complete 4 tests of your mental abilities, including finger tapping, simple math questions (addition, subtraction, multiplication, division), recall of numbers, and recall of objects. It should take 15 minutes total to complete these tests. At the end of the study visit, you will be asked which dose level of the study drug you think you received (high-dose or low-dose). You will also complete a questionnaire about how the study drug may have helped you and how satisfied you are with the study. It should take about 5 minutes to complete the questionnaire. At the end of the study, if you think that taking fentanyl helped to improve your breathing, your doctor will be told, so that you and your doctor may discuss if fentanyl would be helpful to you in the future. Length of Study: Your active participation in this study is over after you complete the last questionnaire. You will be taken off study if intolerable side effects occur or if you are unable to follow study directions. Follow-Up: Fourteen (14) days after your study visit you will be called by the study staff and asked how you are feeling and about any side effects you may be having. This call should last about 10 minutes. This is an investigational study. Fentanyl is FDA approved and commercially available for the treatment of pain. Its use to control shortness of breath is investigational. Up to 30 participants will be enrolled in this study. All will take part at MD Anderson.

Official Title
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A Preliminary Study of Prophylactic Fentanyl Sublingual Spray for Exercise-Induced Breakthrough Dyspnea

Conditions
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Advanced Cancers

Intervention / Treatment
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* Drug: Fentanyl Sublingual Spray
* Procedure: Shuttle Walk Test
* Behavioral: Questionnaires
* Behavioral: Mental Ability Tests
* Behavioral: Phone Call


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of cancer with evidence of active disease Breakthrough dyspnea, defined as dyspnea with an average intensity level over the past 7 days of at least 3/10 on a numeric rating scale upon significant exertion or continuous dyspnea </=7/10 with worsening upon significant exertion Outpatient at MD Anderson Cancer Center seen by the Supportive Care Service, Thoracic Medical Oncology, Cancer Pain Clinic, or Cardiopulmonary clinic Ambulatory and able to walk with or without walking aid On strong opioids with morphine equivalent daily dose of 80-500 mg for at least one week, with stable (i.e. +/- 30%) regular dose over the last 24 hours Karnofsky performance status >/=50% Age 18 or older Able to complete study assessments Exclusion Criteria: Dyspnea at rest >/=7/10 at the time of enrollment Supplemental oxygen requirement >6 L per minute Delirium (i.e. Memorial delirium rating scale >13) History of unstable angina or myocardial infarction 1 month prior to study enrollment Resting heart rate >120 at the time of study enrollment Systolic pressure >180 mmHg or diastolic pressure >100 mmHg at the time of study enrollment History of active opioid abuse within the past 12 months History of allergy to fentanyl Severe anemia (Hb <7g/L) if documented in the last month and not corrected prior to study enrollment* Diagnosis of acute pulmonary embolism within past 2 weeks Diagnosis of pulmonary hypertension Unwilling to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-Dose Fentanyl Spray Group<br>Questionnaires completed at baseline and at end of study visit. Participant performs Shuttle Walk Test before and after receiving low-dose Fentanyl sublingual spray. Four mental ability tests completed after each walk test. Low-dose Fentanyl sprayed into mouth and under tongue one hour after first Shuttle Walk Test. | Drug: Fentanyl Sublingual Spray<br>* Low-dose Fentanyl Goup: 15-25% of the morphine equivalent daily dose (MEDD) sprayed into mouth and under tongue one hour after first Shuttle Walk Test. High-Dose Fentanyl Group: 35-45% of the morphine equivalent daily dose (MEDD) sprayed into mouth and under tongue one hour after first Shuttle Walk Test.<br>* Other names: FSS;Procedure: Shuttle Walk Test<br>* Participants walk back and forth between 2 cones in an indoor hallway for up to 12 minutes. After one hour Fentanyl Spray delivered, then second walk test performed.<br>Behavioral: Questionnaires<br>* Questionnaire completed about any breathing problems or other symptoms participant may be having at baseline. End of study questionnaire asks which dose level of study drug participant thinks they received. Participant also completes a questionnaire about how study drug may have helped them and how satisfied they are with the study. It should take about 5 minutes to complete the questionnaire.<br>* Other names: Surveys;Behavioral: Mental Ability Tests<br>* After each walk test, participant completes 4 tests of their mental abilities. It should take 15 minutes total to complete these tests.<br>Behavioral: Phone Call<br>* Thirty days study visit participant called by study staff. This call should last about 10 minutes.<br>|
| Experimental: High-Dose Fentanyl Spray Group<br>Questionnaires completed at baseline and at end of study visit. Participant performs Shuttle Walk Test before and after receiving high-dose Fentanyl sublingual spray. Four mental ability tests completed after each walk test. High-dose Fentanyl sprayed into mouth and under tongue one hour after first Shuttle Walk Test. | Drug: Fentanyl Sublingual Spray<br>* Low-dose Fentanyl Goup: 15-25% of the morphine equivalent daily dose (MEDD) sprayed into mouth and under tongue one hour after first Shuttle Walk Test. High-Dose Fentanyl Group: 35-45% of the morphine equivalent daily dose (MEDD) sprayed into mouth and under tongue one hour after first Shuttle Walk Test.<br>* Other names: FSS;Procedure: Shuttle Walk Test<br>* Participants walk back and forth between 2 cones in an indoor hallway for up to 12 minutes. After one hour Fentanyl Spray delivered, then second walk test performed.<br>Behavioral: Questionnaires<br>* Questionnaire completed about any breathing problems or other symptoms participant may be having at baseline. End of study questionnaire asks which dose level of study drug participant thinks they received. Participant also completes a questionnaire about how study drug may have helped them and how satisfied they are with the study. It should take about 5 minutes to complete the questionnaire.<br>* Other names: Surveys;Behavioral: Mental Ability Tests<br>* After each walk test, participant completes 4 tests of their mental abilities. It should take 15 minutes total to complete these tests.<br>Behavioral: Phone Call<br>* Thirty days study visit participant called by study staff. This call should last about 10 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Dyspnea Borg Scale (Dyspnea Intensity) | The primary outcome was dyspnea intensity now using the modified Borg scale, which ranges from 0 (no shortness of breath) to 10 (worst possible shortness of breath). We measured the change in modified dyspnea Borg scale (0-10) between the first and second shuttle walk tests. This scale has been validated in multiple studies, with a minimal clinically significant difference of 1 point. | Before and after the first and second shuttle walk tests | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Dyspnea Borg Scale (Dyspnea Unpleasantness) | The modified Borg scale (dyspnea unpleasantness), which ranges from 0 (no shortness of breath) to 10 (worst possible shortness of breath). We measured the change in modified dyspnea Borg scale (0-10) between the first and second shuttle walk tests. | Before and after the first and second shuttle walk tests | 
| Walk Distance | We measured the difference in walk distance (in meters) between the first and second shuttle walk tests. | After the first shuttle walk test and after the second shuttle walk test | 
| Walk Time | We measured the difference in walk time (in minutes) between the first and second shuttle walk tests. | After the first shuttle walk test and after the second shuttle walk test | 
| Fatigue Modified Borg Score | The fatigue modified Borg scale, which ranges from 0 (none) to 10 (worst). We measured the change in modified fatigue Borg scale (0-10) between the first and second shuttle walk tests. | Before and after the first and second shuttle walk tests | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Cancers, Fentanyl Sublingual Spray, Fentanyl SL Spray, FSS, Questionnaires, Surveys, Mental Abilities Test, Phone Call, Shuttle Walk Test