Chronic Obstructive Pulmonary DiseaseNCT01854177
Differentiating the Effects of Substance P and Beta-endorphin
A study testing Aprepitant in people with Chronic Obstructive Pulmonary Disease, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
Trial summary
In previous studies we demonstrated that endogenous opioids (inhibitory neuropeptides) modulate the perception of breathing difficulty in patients with chronic obstructive pulmonary disease (COPD). Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- Aprepitant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to Nov 2013
- Phase
- Interventional
- 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 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- male or female patient 50 years of age or older
- a diagnosis of COPD; former smoker with a history of greater than or equal to 10 pack-years
- a clinical diagnosis of chronic bronchitis (productive cough on most days for a minimum of three months per year for at least two successive years)
- a post-bronchodilator forced expiratory volume in one second (FEV1) greater than or equal to 30% predicted and less than or equal to 80% predicted
- a post-bronchodilator FEV1/forced vital capacity (FVC) ratio less than 70%; and clinically stable COPD.
Who cannot join
- current smoker
- pregnant women
- current or previous (within the past two weeks) use or of a narcotic medication
- any patient who has a concomitant disease that might interfere with study procedures or evaluation including lactose intolerance
- use of a drug that may cause possible drug interaction with aprepitant [including cilostazol, dofetilide, ergot alkaloids, oral or non-oral contraceptives, progestins, ranolazine, reboxetine, warfarin, ziprasidone, anxiolytic medications, anti-depressive medications, cholesterol lowering drugs (e.g., atorvastatin, simvastatin), theophylline, antifungal antibiotics, and macrolide antibiotics]
- use of a contraindicated medication including astemizole, cisapride, pimozide, and terfenadine;
- use of angiotensin converting enzyme inhibitor
Trial locations and contacts
1 site in 1 country.
United States1 site
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756-0001
About this study
Official title: Differentiating the Effects of Substance P and Beta-endorphin in the Perception of Breathlessness During Resistive Load Breathing in Patients With Chronic Obstructive Pulmonary Disease (COPD)
In previous studies we demonstrated that endogenous opioids (inhibitory neuropeptides) modulate the perception of breathing difficulty in patients with chronic obstructive pulmonary disease (COPD). Recently, we found that antagonism of substance P (an excitatory neuropeptide) with aprepitant did not affect the perception of breathing difficulty. However, after administration of aprepitant, blood levels of both substance P(+ 54 ± 39%) and beta-endorphin (+ 27 ± 17%) increased significantly. As these blood levels reflect cellular/tissue activity, we postulated that the concomitant release of excitatory (substance P) and inhibitory (beta-endorphin) neuropeptides had opposing effects (counterbalanced each other) on the perception of breathing difficulty.
The objective of the present study is to further examine the possible role of substance P on the perception of breathlessness. We propose to administer oral aprepitant and oral placebo in a randomized clinical trial in patients with COPD. However, four hours after patients take these medications, intravenous naloxone will be administered in order to block the effects of endogenous opioids (beta-endorphin) on opioid receptors. Five minutes later, patients will breathe thru a tube with fine wire mesh to provoke breathing difficulty, and then provide ratings of the intensity and unpleasantness of breathlessness every minute.
Read more
The two competing hypothesis of the study are:
- if breathlessness ratings with aprepitant/naloxone = placebo/naloxone, then substance P has no effect on perception of breathing difficulty;
- if breathlessness ratings with aprepitant/naloxone ≠ placebo/naloxone, then substance P has an effect on perception of breathing difficulty.
Read the detailed description
This study is a randomized, controlled clinical trial comparing the acute effects of oral aprepitant (selective antagonist of substance P receptor) vs. placebo on ratings of breathlessness during resistive load breathing in patients with COPD. Four hours after randomization, all patients will receive intravenous naloxone (antagonist of opioid receptors) to block the effects of endogenous opioids on perception of breathlessness. The two competing hypothesis of the study are:
Breathing difficulty will be induced by the patient breathing thru a tube with fine wire mesh for approximately 10 - 20 minutes in the laboratory.
Approximately 20 patients with COPD will be recruited from the out-patient clinic at the Dartmouth-Hitchcock Medical Center. The population will consist of female or male adults at least 50 years of age, at least 10 pack-year history of smoking, and a diagnosis of COPD associated with chronic bronchitis based on standard criteria.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- Aprepitant, Placebo
- Keywords
- breathlessness; substance P; beta-endorphin
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Dyspnea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AprepitantDrug
Also called aprepitant 125 mg capsule
PlaceboDrug
Also called inert capsule
| Study group | Role | What they receive |
|---|---|---|
| Aprepitant | Active comparator | Aprepitant 125 mg Receives: Drug: Aprepitant |
| Placebo | Placebo comparator | Inert capsule Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Unpleasantness of Breathlessness
Unpleasantness of breathlessness was reported each minute by the patient on a visual analog scale. The scale range is 0-10 where 0 = No breathlessness and 10 = Severe breathlessness. The measures were collected up to 20 minutes per visit and combined for a final score. Total minimum score = 0, total maximum score 200. Data is collected during Resistive Load Breathing at Period 1 (Day 3 or 4) and Period 2 (Day 5, 6 or 7) during which either Placebo or Aprepitant was administered. A high unpleasantness indicates that breathing difficulty feels very bad or terrifying regardless of whether the intensity is high or low
Measured: Visit 2 (Approximately Day 3 where either Placebo or Aprepitant was administered).and Visit 3 (approximately Day 6 where either Placebo or Aprepitant was administered)
Intensity of Breathlessness
Intensity of Breathlessness was recorded on a visual analog scale. The scale range is 0-10 where 0 = minimum and 10 = maximal intensity. At each visit, participants were asked to report unpleasantness at 1 minute intervals. The measures were collected up to 20 minutes per visit and combined for a final score. Total minimum score = 0, total maximum score 200. Data is collected during Resistive Load Breathing at Period 1 (Day 3 or 4) and Period 2 (Day 5, 6 or 7) during which either Placebo or Aprepitant was administered.
Measured: Visit 2 (Approximately Day 3 where either Placebo or Aprepitant was administered).and Visit 3 (approximately Day 6 where either Placebo or Aprepitant was administered)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2013 (estimated)
- Study startJul 2013
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- More trials run by Dartmouth-Hitchcock Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Donald A. Mahler, Dartmouth-Hitchcock Medical Center
- Investigators
- Donald A Mahler, M.D., Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01854177
- Sponsor's protocol ID
- CPHS#23992
- Status last verified
- Aug 2018
- First submitted
- 13 May 2013
- Last updated
- 30 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Differentiating the Effects of Substance P and Beta-endorphin in the Perception of Breathlessness During Resistive Load Breathing in Patients With Chronic Obstructive Pulmonary Disease (COPD)
- ClinicalTrials.gov ID
- NCT01854177
- Acronym / sponsor ID
- CPHS#23992
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- breathlessness; substance P; beta-endorphin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 15 May 2013 (estimated)
- Results
- Posted 30 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In previous studies we demonstrated that endogenous opioids (inhibitory neuropeptides) modulate the perception of breathing difficulty in patients with chronic obstructive pulmonary disease (COPD). Recently, we found that antagonism of substance P (an excitatory neuropeptide) with aprepitant did not affect the perception of breathing difficulty. However, after administration of aprepitant, blood levels of both substance P(+ 54 ± 39%) and beta-endorphin (+ 27 ± 17%) increased significantly. As these blood levels reflect cellular/tissue activity, we postulated that the concomitant release of excitatory (substance P) and inhibitory (beta-endorphin) neuropeptides had opposing effects (counterbalanced each other) on the perception of breathing difficulty.
The objective of the present study is to further examine the possible role of substance P on the perception of breathlessness. We propose to administer oral aprepitant and oral placebo in a randomized clinical trial in patients with COPD. However, four hours after patients take these medications, intravenous naloxone will be administered in order to block the effects of endogenous opioids (beta-endorphin) on opioid receptors. Five minutes later, patients will breathe thru a tube with fine wire mesh to provoke breathing difficulty, and then provide ratings of the intensity and unpleasantness of breathlessness every minute.
The two competing hypothesis of the study are:
- if breathlessness ratings with aprepitant/naloxone = placebo/naloxone, then substance P has no effect on perception of breathing difficulty;
- if breathlessness ratings with aprepitant/naloxone ≠ placebo/naloxone, then substance P has an effect on perception of breathing difficulty.
Detailed description
This study is a randomized, controlled clinical trial comparing the acute effects of oral aprepitant (selective antagonist of substance P receptor) vs. placebo on ratings of breathlessness during resistive load breathing in patients with COPD. Four hours after randomization, all patients will receive intravenous naloxone (antagonist of opioid receptors) to block the effects of endogenous opioids on perception of breathlessness. The two competing hypothesis of the study are:
Breathing difficulty will be induced by the patient breathing thru a tube with fine wire mesh for approximately 10 - 20 minutes in the laboratory.
Approximately 20 patients with COPD will be recruited from the out-patient clinic at the Dartmouth-Hitchcock Medical Center. The population will consist of female or male adults at least 50 years of age, at least 10 pack-year history of smoking, and a diagnosis of COPD associated with chronic bronchitis based on standard criteria.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aprepitant | Active comparator | Drug: AprepitantAprepitant 125 mg |
| Placebo | Placebo comparator | Drug: PlaceboInert capsule |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- male or female patient 50 years of age or older
- a diagnosis of COPD; former smoker with a history of greater than or equal to 10 pack-years
- a clinical diagnosis of chronic bronchitis (productive cough on most days for a minimum of three months per year for at least two successive years)
- a post-bronchodilator forced expiratory volume in one second (FEV1) greater than or equal to 30% predicted and less than or equal to 80% predicted
- a post-bronchodilator FEV1/forced vital capacity (FVC) ratio less than 70%; and clinically stable COPD.
Key exclusion criteria (7 listed)
- current smoker
- pregnant women
- current or previous (within the past two weeks) use or of a narcotic medication
- any patient who has a concomitant disease that might interfere with study procedures or evaluation including lactose intolerance
- use of a drug that may cause possible drug interaction with aprepitant [including cilostazol, dofetilide, ergot alkaloids, oral or non-oral contraceptives, progestins, ranolazine, reboxetine, warfarin, ziprasidone, anxiolytic medications, anti-depressive medications, cholesterol lowering drugs (e.g., atorvastatin, simvastatin), theophylline, antifungal antibiotics, and macrolide antibiotics]
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AprepitantAlso: aprepitant 125 mg capsule | Drug | Aprepitant |
| PlaceboAlso: inert capsule | Drug | Placebo |
Primary outcome
Unpleasantness of Breathlessness
Time frame: Visit 2 (Approximately Day 3 where either Placebo or Aprepitant was administered).and Visit 3 (approximately Day 6 where either Placebo or Aprepitant was administered)
Unpleasantness of breathlessness was reported each minute by the patient on a visual analog scale. The scale range is 0-10 where 0 = No breathlessness and 10 = Severe breathlessness. The measures were collected up to 20 minutes per visit and combined for a final score. Total minimum score = 0, total maximum score 200. Data is collected during Resistive Load Breathing at Period 1 (Day 3 or 4) and Period 2 (Day 5, 6 or 7) during which either Placebo or Aprepitant was administered. A high unpleasantness indicates that breathing difficulty feels very bad or terrifying regardless of whether the intensity is high or low
Intensity of Breathlessness
Time frame: Visit 2 (Approximately Day 3 where either Placebo or Aprepitant was administered).and Visit 3 (approximately Day 6 where either Placebo or Aprepitant was administered)
Intensity of Breathlessness was recorded on a visual analog scale. The scale range is 0-10 where 0 = minimum and 10 = maximal intensity. At each visit, participants were asked to report unpleasantness at 1 minute intervals. The measures were collected up to 20 minutes per visit and combined for a final score. Total minimum score = 0, total maximum score 200. Data is collected during Resistive Load Breathing at Period 1 (Day 3 or 4) and Period 2 (Day 5, 6 or 7) during which either Placebo or Aprepitant was administered.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donald A Mahler, M.D. principal investigator
Dartmouth-Hitchcock Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Aprepitant in people with Chronic Obstructive Pulmonary Disease, run by Dartmouth-Hitchcock 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 5 inclusion and 7 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 30 Oct 2018. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Oct 2018). 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?
Unpleasantness of Breathlessness (time frame: Visit 2 (Approximately Day 3 where either Placebo or Aprepitant was administered).and Visit 3 (approximately Day 6 where either Placebo or Aprepitant was administered)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Oct 2018; AzTrials last refreshed its copy on 6 Nov 2026.