Hyperalgesia and Pain

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.

Study Overview

• Status: Completed
• Conditions: Hyperalgesia
• Intervention / Treatment: Drug: Nitrous Oxide; Drug: Nitrous Oxide

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 Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Erlangen, Germany, 91054
    • University of Erlangen - Nürnberg
  • Erlangen, Germany
    • University of Erlangen - Nürnberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Tested drug; Remifentanil at 0.1 µg/kg/min Tested drug (N2O 35%): 35%/15%/50% N2O/N2/O2	Drug: Nitrous Oxide; 35%; Drug: Nitrous Oxide; 50%; Other Names: Kalinox
ACTIVE_COMPARATOR: Gas Active control; Remifentanil at 0.1 µg/kg/min Gas active control (N2O 50%):50%/50% N2O/O2	Drug: Nitrous Oxide; 35%; Drug: Nitrous Oxide; 50%; Other Names: Kalinox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hyperalgesia	- Hyperalgesia will be assessed by using a metal rod,(in unit cm).	at T0, T10, T25, T40, T55, T70, T95, T110, T125, T140 and T155 minutes at each experimental session which will last half day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
transcutaneous oxygen saturation	By monitoring pulse oximetry device	From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
respiration rate	Respiration rate	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	From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
Heart rate	Measured by cardioscope	From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day
sedation score	sedation score	From T0 to T160 minutes, at 5 minute intervals at each experimental session which will last half day

Collaborators and Investigators

• Sponsor: Air Liquide Santé International
• Collaborators: ORION Clinical Services
• Investigators: Principal Investigator: Andreas WEHRFRITZ, MD, University of Erlangen-Nürnberg - Germany

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (ACTUAL): April 1, 2012
• Study Completion (ACTUAL): April 1, 2012

Study Registration Dates

• First Submitted: November 30, 2011
• First Submitted That Met QC Criteria: April 19, 2012
• First Posted (ESTIMATE): April 20, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): April 20, 2012
• Last Update Submitted That Met QC Criteria: April 19, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Hyperalgesia and pain
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Sensation Disorders; Somatosensory Disorders; Hyperalgesia; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Anesthetics, Inhalation; Nitrous Oxide
• Other Study ID Numbers: 2011-000966-37