Hyperalgesia and Pain
Condition: Hyperalgesia
MeSH terms: Hyperalgesia
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Nitrous Oxide; Nitrous Oxide
Intervention type(s): Drug; Drug
Intervention description(s): 35%; 50%
Other intervention name(s): Kalinox
Intervention MeSH terms: Nitrous Oxide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Hyperalgesia and pain