Acute PainPhase 1/2AEROMORPH1NCT01975753
First Evaluation of Morphine Hydrochloride by Nebulisation in Healthy Volunteers
A Phase 1/2 study testing Morphine and Fentanyl in people with Acute Pain, run by University Hospital, Rouen at 1 site in France.
Trial summary
Acute pain relief in emergency setting is still a public health priority. Pain is the primary reason for emergency room use, but the situation of "oligo-analgesia" persists in all countries. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Acute Pain
- What is being tested?
- Morphine and Fentanyl
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteFrance
- Study dates
- 13 May 2014to 2 May 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Sex: We choose to include 50% of men and 50% women (this covariate will be included in the parameters to balance the randomization list).
- Age: Healthy volunteers will be between 18 to 60 years
- Body mass index (BMI) between 19 and 29 kg / m²
- effective contraception methods in women of childbearing age
- Signature of informed consent
- Affiliation to a social security scheme
Who cannot join
- Taking painkillers long-term
- Taking psychotropic drugs long-term
- Healthy volunteers with chronic pain
- Drug addiction
- Chronic neuropsychiatric pathology which may alter the pain threshold
- Active Smoking
Show all 19Show fewer
- Chronic obstructive or restrictive respiratory pathology
- Progressive known pathology (hypertension, kidney failure, heart, liver ...)
- Chronic treatments are prohibited except oral contraception
- Delirium or dementia, people who did not understand the pain scales
- Lack of understanding of the French language
- pregnancy and lactation
- Poor venous capital
- History of abnormal reaction at a local / regional anesthesia
- Heart rate : HR <50 bpm
- Hypotension TAsyst with systolic blood pressure <100 mm Hg
- Atrioventricular block (PR interval> 200 ms)
- Period exclusion of another biomedical research
- Nobody placed under judicial protection, guardianship
Trial locations and contacts
1 site in 1 country.
About this study
Official title: First Evaluation of Morphine Hydrochloride by Nebulisation Compared to Intravenous Route in Healthy Volunteers: Preliminary Study Dose
Acute pain relief in emergency setting is still a public health priority. Pain is the primary reason for emergency room use, but the situation of "oligo-analgesia" persists in all countries. Intravenous morphine titration has become the standard method for severe acute pain management in the emergency department, but it is still insufficiently implemented. Deviations from the recommended protocol are common: initial additional loading doses, unusually extended intervals between bolus, premature discontinuation. Several factors contribute to these difficulties: heaviness of its setting up, especially in overcrowding case, procedure rigidity, high consumption of nursing time. This method requires a systematic intravenously route, which has several inconvenients: algogenic procedures, coupled initial diagnostic venous sampling (delay for analgesia), excessive "medicalization" of ambulatory patients (risk of infection and less mobility in the emergency department). An alternative to reduce the analgesic latency in emergency department, without losing the benefits of tolerance and safety should be welcome. The inhaled route looks promising, but has yet not been enough evaluated in adults, and even less in the emergency room. Aerosol techniques change from one study to another (molecules, materials, doses, painful intensities included, judgment criteria and assessment times). A morphine titration by aerosol therapy could be an interesting alternative to the standard method disadvantages, using faster, painless and easier procedures, leading to "demedicalization".
To the need for stronger fundamentals, an additional study was designed in healthy volunteers. The objective is to compare the titration of intravenous morphine titration aerosol in moderate acute pain caused by electrostimulation.
To purchase this aim, we first need to determine accurately the smallest dose of effective and well tolerated inhaled morphine, to provide the "bolus" dose we have to repeat by titration, which is still currently unknown. This dose is called ED50, it's the effective dose for at least 50% of healthy volunteers relieved. ED50 for intravenous morphine is also needed to be established, unknown in this indication. The determination of these two parallel ED50 would allow a reliable conversion factor between the two routes of administration for morphine "bolus", which can then be tested in comparative titrations. To validate our induced pain model in healthy volunteers, we also have chosen to fix in these conditions the ED50 of fentanyl that the effective dose by nebulization is better known. This study would also describe the pharmacokinetics of inhaled morphine and its derivatives after a single spray.
- Conditions
- Acute Pain
- Keywords
- pain
- Medical subject headings
- Acute Pain, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous morphine | Active comparator | one bolus of intravenous morphine Receives: Drug: Morphine |
| nebulized morphine | Experimental | one "nebulized" bolus of morphine Receives: Drug: Morphine |
| fentanyl | Active comparator | one "nebulized" bolus of fentanyl Receives: Drug: Fentanyl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effective doses of intravenous morphine hydrochloride "bolus" and nebulized "bolus" in 50% of healthy painful volunteers
The primary endpoint is efficacy: relief from healthy volunteers thanks to VAS decreasing, defined as ≤ 20 (100mm). At the end of the study the dose chosen is the effective dose for 50% of the volunteers.
Measured: 7 min
Secondary outcomes (1)
safety
Check tolerance of aerosols on respiratory and systemically 2. Describe the pharmacokinetics of a "bolus" and a titration of morphine hydrochloride aerosol standardized, and of all its metabolites 3. Establish the concentration-effect relationship of a spray "bolus" and of a titration of morphine hydrochloride standardized (for the analgesic effect) using a pharmacokinetic / pharmacodynamic model (PK / PD) and mathematical modeling 4. Methodological validation by determining the ED50 of a inhaled fentanyl "bolus" 5. Establish pharmacokinetic bases that can provide a secure further study in the emergency room, targeting patients with severe spontaneous acute pain
Measured: 7 min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2013 (estimated)
- Study start13 May 2014
- Primary completion2 May 2018
- Study completion2 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute PainStudies of the same condition, open and under way.
- More trials run by University Hospital, RouenThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01975753
- Sponsor's protocol ID
- 2013/004/HP
- Acronym
- AEROMORPH1
- Status last verified
- Oct 2019
- First submitted
- 29 Oct 2013
- Last updated
- 24 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lvovschi V, Aubrun F, Bonnet P, Bouchara A, Bendahou M, Humbert B, Hausfater P, Riou B. Intravenous morphine titration to treat severe pain in the ED. Am J Emerg Med. 2008 Jul;26(6):676-82. doi: 10.1016/j.ajem.2007.10.025.
PubMed 18606320Blum CA, Velly L, Brochet C, Ziegler F, Tavolacci MP, Hausfater P, Lvovschi VE. Relevance of cortisol and copeptin blood concentration changes in an experimental pain model. Sci Rep. 2022 Mar 19;12(1):4767. doi: 10.1038/s41598-022-08657-4.
PubMed 35306524
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First Evaluation of Morphine Hydrochloride by Nebulisation Compared to Intravenous Route in Healthy Volunteers: Preliminary Study Dose
- ClinicalTrials.gov ID
- NCT01975753
- Acronym / sponsor ID
- AEROMORPH1 / 2013/004/HP
- Conditions
- Acute Pain
- Keywords
- pain
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Study start
- 13 May 2014 (actual)
- Primary completion
- 2 May 2018 (actual)
- Study completion
- 2 May 2018 (actual)
- First posted
- 5 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Acute pain relief in emergency setting is still a public health priority. Pain is the primary reason for emergency room use, but the situation of "oligo-analgesia" persists in all countries. Intravenous morphine titration has become the standard method for severe acute pain management in the emergency department, but it is still insufficiently implemented. Deviations from the recommended protocol are common: initial additional loading doses, unusually extended intervals between bolus, premature discontinuation. Several factors contribute to these difficulties: heaviness of its setting up, especially in overcrowding case, procedure rigidity, high consumption of nursing time. This method requires a systematic intravenously route, which has several inconvenients: algogenic procedures, coupled initial diagnostic venous sampling (delay for analgesia), excessive "medicalization" of ambulatory patients (risk of infection and less mobility in the emergency department). An alternative to reduce the analgesic latency in emergency department, without losing the benefits of tolerance and safety should be welcome. The inhaled route looks promising, but has yet not been enough evaluated in adults, and even less in the emergency room. Aerosol techniques change from one study to another (molecules, materials, doses, painful intensities included, judgment criteria and assessment times). A morphine titration by aerosol therapy could be an interesting alternative to the standard method disadvantages, using faster, painless and easier procedures, leading to "demedicalization".
To the need for stronger fundamentals, an additional study was designed in healthy volunteers. The objective is to compare the titration of intravenous morphine titration aerosol in moderate acute pain caused by electrostimulation.
To purchase this aim, we first need to determine accurately the smallest dose of effective and well tolerated inhaled morphine, to provide the "bolus" dose we have to repeat by titration, which is still currently unknown. This dose is called ED50, it's the effective dose for at least 50% of healthy volunteers relieved. ED50 for intravenous morphine is also needed to be established, unknown in this indication. The determination of these two parallel ED50 would allow a reliable conversion factor between the two routes of administration for morphine "bolus", which can then be tested in comparative titrations. To validate our induced pain model in healthy volunteers, we also have chosen to fix in these conditions the ED50 of fentanyl that the effective dose by nebulization is better known. This study would also describe the pharmacokinetics of inhaled morphine and its derivatives after a single spray.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Intravenous morphine | Active comparator | Drug: Morphineone bolus of intravenous morphine |
| nebulized morphine | Experimental | Drug: Morphineone "nebulized" bolus of morphine |
| fentanyl | Active comparator | Drug: Fentanylone "nebulized" bolus of fentanyl |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Sex: We choose to include 50% of men and 50% women (this covariate will be included in the parameters to balance the randomization list).
- Age: Healthy volunteers will be between 18 to 60 years
- Body mass index (BMI) between 19 and 29 kg / m²
- effective contraception methods in women of childbearing age
- Signature of informed consent
Key exclusion criteria (19 listed)
- Taking painkillers long-term
- Taking psychotropic drugs long-term
- Healthy volunteers with chronic pain
- Drug addiction
- Chronic neuropsychiatric pathology which may alter the pain threshold
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 |
|---|---|---|
| Morphine | Drug | Intravenous morphine, nebulized morphine |
| Fentanyl | Drug | fentanyl |
Primary outcome
Effective doses of intravenous morphine hydrochloride "bolus" and nebulized "bolus" in 50% of healthy painful volunteers
Time frame: 7 min
The primary endpoint is efficacy: relief from healthy volunteers thanks to VAS decreasing, defined as ≤ 20 (100mm). At the end of the study the dose chosen is the effective dose for 50% of the volunteers.
1 secondary outcome
safety
Time frame: 7 min
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2019.
- Background: PubMed 18606320Lvovschi V, Aubrun F, Bonnet P, Bouchara A, Bendahou M, Humbert B, Hausfater P, Riou B. Intravenous morphine titration to treat severe pain in the ED. Am J Emerg Med. 2008 Jul;26(6):676-82. doi: 10.1016/j.ajem.2007.10.025.
- Derived from this study: PubMed 35306524Blum CA, Velly L, Brochet C, Ziegler F, Tavolacci MP, Hausfater P, Lvovschi VE. Relevance of cortisol and copeptin blood concentration changes in an experimental pain model. Sci Rep. 2022 Mar 19;12(1):4767. doi: 10.1038/s41598-022-08657-4.
Related trials for Acute Pain
Not yet recruiting
Human Experimental Models of Pain (HEMP)
Acute Pain
RecruitingPhase 2
REctus Sheath Trial
Acute Pain, Postoperative Pain, Acute
Not yet recruitingPhase 2
A Clinical Trial of MK-6916 in Participants With Pain After Bunion Removal Surgery (MK-6916-007)
Pain Management
Not yet recruitingPhase 2
Investigating the Analgesic Potential of (2R,6R)-HNK in Acute Pain in Healthy Volunteers
Healthy Volunteers
Not yet recruiting
Post-operative Pain and Clinical Outcome After Single-cone Obturation With a Calcium Silicate-based Versus Epoxy Resin Sealer
Post Operative Pain, Acute, Irreversible Pulpitis (Toothache)
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Morphine and Fentanyl in people with Acute Pain, run by University Hospital, Rouen at 1 site in France.
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 6 inclusion and 19 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 24 Oct 2019. 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 France. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Effective doses of intravenous morphine hydrochloride "bolus" and nebulized "bolus" in 50% of healthy painful volunteers (time frame: 7 min). 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 NCT01975753, which also lists 2 linked publications.
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 24 Oct 2019.