Clinical trial NCT01581450: Hyperalgesia and Pain
Official title: Evaluation of Antihyperalgesic and Analgesic Effects of 35% Nitrous Oxide in a Human Model of Electrically Evoked Hyperalgesia and Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hyperalgesia
Keywords: Hyperalgesia and pain
Lead sponsor: Air Liquide Santé International
Sponsor class: INDUSTRY
Collaborators: name: ORION Clinical Services
First posted: 2012-04-20
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Hyperalgesia
timeFrame: 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:
measure: transcutaneous oxygen saturation
timeFrame: From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
measure: respiration rate
timeFrame: From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
measure: systolic and diastolic blood pressures
timeFrame: From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
measure: Heart rate
timeFrame: From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
measure: sedation score
timeFrame: From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: University of Erlangen - Nürnberg
city: Erlangen
country: Germany
facility: University of Erlangen - Nürnberg
Study officials:
affiliation: University of Erlangen-Nürnberg, Germany
name: Andreas WEHRFRITZ, MD
role: PRINCIPAL_INVESTIGATOR
References: