HyperalgesiaPhase 1NCT01581450
Hyperalgesia and Pain
A Phase 1 study testing Nitrous Oxide in people with Hyperalgesia, run by Air Liquide Santé International at 2 sites in Germany.
Trial summary
Evaluation of the effects of 35%/15%/50% N2O/N2/O2 mixtures on the area of hyperalgesia induced by remifentanil in the CCES (Continuous Cutaneous Electrical Stimulation) model in 20 healthy volunteers. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Hyperalgesia
- What is being tested?
- Nitrous Oxide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesGermany
- Study dates
- Jan 2012to Apr 2012
- Phase
- Phase 1
- 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 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Caucasian healthy male
- Able to feel a distinct pin-pick sensation on normal skin
- Subject willing and able to complete the requirements of this study
- Written informed consent signed prior to any study related procedures
Who cannot join
- History of any past or current renal, hepatic, cardiovascular, pulmonary, gastrointestinal, metabolic, endocrine haematological, neurological, psychiatric disease or other disorders
- Any significant history of allergic disease
- Acute skin disease, lesions, acute sunburn, extensive tattoos or scars
- Donation of blood within the previous 3 months
- participation in any other clinical study within the previous 4 weeks.
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
University of Erlangen - Nürnberg
Erlangen, 91054
University of Erlangen - Nürnberg
Erlangen
About this study
Official title: Evaluation of Antihyperalgesic and Analgesic Effects of 35% Nitrous Oxide in a Human Model of Electrically Evoked Hyperalgesia and Pain
Evaluation of the effects of 35%/15%/50% N2O/N2/O2 mixtures on the area of hyperalgesia induced by remifentanil in the CCES (Continuous Cutaneous Electrical Stimulation) model in 20 healthy volunteers.
The duration of participation for each volunteer is expected to be around 9 weeks with the performance of 4 experimental session 2 weeks apart.
The selection visit will last half a day; each experimental session will last half a day; the study end will last 2 hours maximum.
Read the detailed description
Single site, exploratory, comparative, double-blind, randomised, cross-over study. Three physicians will be involved in the conduct of this study:
- Physician 1 will include and randomise the subjects, prepare and administer the study products (namely Investigational Medicinal Products (IMPs)) in an open manner and will assess subject safety.
- Physician 2, kept IMP blinded, will perform all evaluation measurements and sedation assessments during all experimental sessions. Physician 2 will always be the same person throughout the whole study period.
- Physician 3 will be available if needed to reinforce subject safety
Design: A group of 20 assessable subjects who will undergo 4 randomised experimental sessions of CCES on 4 separate study days, 2 weeks apart preceded by a 2 week period between selection and first experimental session and followed by a 1 week period between last experimental session and study end.
After the selection visit, each visit corresponds to one of the 4 experimental sessions named A, B, C, D differing by the gas mixture inhaled and the intravenous medicine administered.
The order of these experimental sessions A, B, C, D, will be assigned according to a pre-established list that the investigator will not know.
Each experimental session includes a set-up-phase followed by an evaluation phase.
The set up phase will last 20 mn during each an electrical stimulation will generate a spontaneous pain: every 2 minutes the electrical stimulation will increase and the subject will be asked to rate the pain on a visual scale from 0 to 100. When a stable levels of pain intensity will be reached, the regimen of the electrical stimulation will be kept constant up to the end of the experimental session.
The Evaluation phase will last 160 mn : the electrical stimulation will be constant during 160 mn as detailed above. During this phase the subject will inhale a gas mixture with a face mask during 60 minutes combined with an intravenous administration of medicine during 30 mn starting at the same time.
Every 5 minutes the subject will be asked to rate the pain and at predefined times the spontaneous pain and the area of allodynia and hyperalgesia will be measured and recorded as well as safety parameters (transcutaneous oxygen saturation, respiratory parameters, sedation score, blood pressure and heart rate).
The 4 experimental sessions named A, B, C, D differ by the gas mixture inhaled and the intravenous medicine administered.
For the placebo session, inhaled gas mixture will be 50%/50% N2/O2 and intravenous administration will be an isotonic saline solution.
For the three other sessions, inhaled gas mixture will differ from a session to the other one (35%/15%/50% N2O/N2/O2 or 50%/50% N2/O2 or 50%/50% N2O/O2), and remifentanil will be administered intravenously at each of these sessions.
- Conditions
- Hyperalgesia
- Being tested
- Nitrous Oxide
- Keywords
- Hyperalgesia and pain
- Medical subject headings
- Hyperalgesia, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitrous OxideDrug
35%
Nitrous OxideDrug
Also called Kalinox
50%
| Study group | Role | What they receive |
|---|---|---|
| Tested drug | Experimental | Remifentanil at 0.1 µg/kg/min Tested drug (N2O 35%): 35%/15%/50% N2O/N2/O2 Receives: Drug: Nitrous Oxide |
| Gas Active control | Active comparator | Remifentanil at 0.1 µg/kg/min Gas active control (N2O 50%):50%/50% N2O/O2 Receives: Drug: Nitrous Oxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hyperalgesia
- Hyperalgesia will be assessed by using a metal rod,(in unit cm).
Measured: at T0, T10, T25, T40, T55, T70, T95, T110, T125, T140 and T155 minutes at each experimental session which will last half day
Secondary outcomes (5)
transcutaneous oxygen saturation
By monitoring pulse oximetry device
Measured: From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
respiration rate
Respiration rate
Measured: From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
systolic and diastolic blood pressures
systolic and diastolic blood pressures
Measured: From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
Heart rate
Measured by cardioscope
Measured: From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
sedation score
sedation score
Measured: From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2012 (estimated)
- Study startJan 2012
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HyperalgesiaStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Air Liquide Santé International
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ORION Clinical Services
- Responsible party
- Sponsor
- Investigators
- Andreas WEHRFRITZ, MD, Principal investigator, University of Erlangen-Nürnberg, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01581450
- Sponsor's protocol ID
- 2011-000966-37
- Status last verified
- Sep 2025
- First submitted
- 30 Nov 2011
- Last updated
- 11 Sep 2025
- Results posted
- No
Publications
Wehrfritz A, Bauer M, Noel N, Ramirez-Gil JF, Ihmsen H, Prottengeier J, Schuttler J, Bessiere B. Evaluation of antihyperalgesic and analgesic effects of 35% nitrous oxide when combined with remifentanil: A randomised phase 1 trial in volunteers. Eur J Anaesthesiol. 2021 Dec 1;38(12):1230-1241. doi: 10.1097/EJA.0000000000001468.
PubMed 34735395
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Antihyperalgesic and Analgesic Effects of 35% Nitrous Oxide in a Human Model of Electrically Evoked Hyperalgesia and Pain
- ClinicalTrials.gov ID
- NCT01581450
- Acronym / sponsor ID
- 2011-000966-37
- Conditions
- Hyperalgesia
- Keywords
- Hyperalgesia and pain
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Air Liquide Santé InternationalIndustry (pharma, biotech, devices)
- Collaborators
- ORION Clinical Services
- Study start
- Jan 2012
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 20 Apr 2012 (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.
Evaluation of the effects of 35%/15%/50% N2O/N2/O2 mixtures on the area of hyperalgesia induced by remifentanil in the CCES (Continuous Cutaneous Electrical Stimulation) model in 20 healthy volunteers.
The duration of participation for each volunteer is expected to be around 9 weeks with the performance of 4 experimental session 2 weeks apart.
The selection visit will last half a day; each experimental session will last half a day; the study end will last 2 hours maximum.
Detailed description
Single site, exploratory, comparative, double-blind, randomised, cross-over study. Three physicians will be involved in the conduct of this study:
- Physician 1 will include and randomise the subjects, prepare and administer the study products (namely Investigational Medicinal Products (IMPs)) in an open manner and will assess subject safety.
- Physician 2, kept IMP blinded, will perform all evaluation measurements and sedation assessments during all experimental sessions. Physician 2 will always be the same person throughout the whole study period.
- Physician 3 will be available if needed to reinforce subject safety
Design: A group of 20 assessable subjects who will undergo 4 randomised experimental sessions of CCES on 4 separate study days, 2 weeks apart preceded by a 2 week period between selection and first experimental session and followed by a 1 week period between last experimental session and study end.
After the selection visit, each visit corresponds to one of the 4 experimental sessions named A, B, C, D differing by the gas mixture inhaled and the intravenous medicine administered.
The order of these experimental sessions A, B, C, D, will be assigned according to a pre-established list that the investigator will not know.
Each experimental session includes a set-up-phase followed by an evaluation phase.
The set up phase will last 20 mn during each an electrical stimulation will generate a spontaneous pain: every 2 minutes the electrical stimulation will increase and the subject will be asked to rate the pain on a visual scale from 0 to 100. When a stable levels of pain intensity will be reached, the regimen of the electrical stimulation will be kept constant up to the end of the experimental session.
The Evaluation phase will last 160 mn : the electrical stimulation will be constant during 160 mn as detailed above. During this phase the subject will inhale a gas mixture with a face mask during 60 minutes combined with an intravenous administration of medicine during 30 mn starting at the same time.
Every 5 minutes the subject will be asked to rate the pain and at predefined times the spontaneous pain and the area of allodynia and hyperalgesia will be measured and recorded as well as safety parameters (transcutaneous oxygen saturation, respiratory parameters, sedation score, blood pressure and heart rate).
The 4 experimental sessions named A, B, C, D differ by the gas mixture inhaled and the intravenous medicine administered.
For the placebo session, inhaled gas mixture will be 50%/50% N2/O2 and intravenous administration will be an isotonic saline solution.
For the three other sessions, inhaled gas mixture will differ from a session to the other one (35%/15%/50% N2O/N2/O2 or 50%/50% N2/O2 or 50%/50% N2O/O2), and remifentanil will be administered intravenously at each of these sessions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tested drug | Experimental | Drug: Nitrous OxideRemifentanil at 0.1 µg/kg/min Tested drug (N2O 35%): 35%/15%/50% N2O/N2/O2 |
| Gas Active control | Active comparator | Drug: Nitrous OxideRemifentanil at 0.1 µg/kg/min Gas active control (N2O 50%):50%/50% N2O/O2 |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Caucasian healthy male
- Able to feel a distinct pin-pick sensation on normal skin
- Subject willing and able to complete the requirements of this study
- Written informed consent signed prior to any study related procedures
Key exclusion criteria (5 listed)
- History of any past or current renal, hepatic, cardiovascular, pulmonary, gastrointestinal, metabolic, endocrine haematological, neurological, psychiatric disease or other disorders
- Any significant history of allergic disease
- Acute skin disease, lesions, acute sunburn, extensive tattoos or scars
- Donation of blood within the previous 3 months
- participation in any other clinical study within the previous 4 weeks.
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 |
|---|---|---|
| Nitrous Oxide35% | Drug | Tested drug |
| Nitrous OxideAlso: Kalinox50% | Drug | Gas Active control |
Primary outcome
Hyperalgesia
Time frame: at T0, T10, T25, T40, T55, T70, T95, T110, T125, T140 and T155 minutes at each experimental session which will last half day
- Hyperalgesia will be assessed by using a metal rod,(in unit cm).
5 secondary outcomes
transcutaneous oxygen saturation
Time frame: From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
respiration rate
Time frame: From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
systolic and diastolic blood pressures
Time frame: From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
Heart rate
Time frame: From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
sedation score
Time frame: From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
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 11 Sep 2025.
- Results publication: PubMed 34735395Wehrfritz A, Bauer M, Noel N, Ramirez-Gil JF, Ihmsen H, Prottengeier J, Schuttler J, Bessiere B. Evaluation of antihyperalgesic and analgesic effects of 35% nitrous oxide when combined with remifentanil: A randomised phase 1 trial in volunteers. Eur J Anaesthesiol. 2021 Dec 1;38(12):1230-1241. doi: 10.1097/EJA.0000000000001468.
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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.
Andreas WEHRFRITZ, MD principal investigator
University of Erlangen-Nürnberg, Germany
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nitrous Oxide in people with Hyperalgesia, run by Air Liquide Santé International at 2 sites in Germany.
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 4 inclusion and 5 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 11 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. 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 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.
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?
Hyperalgesia (time frame: at T0, T10, T25, T40, T55, T70, T95, T110, T125, T140 and T155 minutes at each experimental session which will last half day). 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 NCT01581450, 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 11 Sep 2025.