Can Fentanyl Lead to Opioid-induced Hyperalgesia in Healthy Volunteers?

Study Overview
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Brief Summary
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The purpose of this study is to examine whether two clinically sensible dose regimen of fentanyl (low dose vs. high dose) lead to different pain scores as measured by the nonverbal rating scale (NRS) in healthy volunteers at 4.5 to 6.5 hours after fentanyl application. Pain modalities tested will include transdermal electrical stimulation and cold pressor pain. The investigators hypothesize that the high dose fentanyl group will have an increase of approximately 20% in the NRS.

Official Title
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Can Fentanyl Lead to Opioid-induced Hyperalgesia in Healthy Volunteers? A Prospective, Randomized, Double-blinded Crossover Study

Conditions
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Healthy

Intervention / Treatment
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* Drug: Fentanyl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy (ASA I-II) male volunteers Age > 18 years BMI 18 - 25 kg/m2 Exclusion Criteria: Volunteers unable to give written informed consent Known drug allergies or intolerance to fentanyl Known drug allergies or intolerance to morphine and other opiates Recreational drug addiction or abuse Opiate use in the last month Volunteers taking confounding medication (analgesics, antihistamines, calcium or potassium channel blockers) in the last month History of motion sickness, neuropathy, chronic pain, neuromuscular or psychiatric disease Patients with renal failure (clearance < 30 ml/min) obstructive sleep apnea syndrome (OSAS) Indication for Rapid Sequence Induction Patients not understanding German, French, Italian or English

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fentanyl high dose<br>Fentanyl 10mcg/kg of bodyweight | Drug: Fentanyl<br> <br> |
| Active Comparator: Fentanyl low dose<br>Fentanyl 1mcg/kg of bodyweight | Drug: Fentanyl<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COMPOSITE of pain scores as measured by the nonverbal rating scale (NRS) at 15 minute intervals within the timeframe specified below. |  | 4.5 to 6.5h after begin of fentanyl infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain as measured by the nonverbal rating scale |  | 0-2h after begin of fentanyl infusion at 15 min intervals | 
| cold pressor pain |  | at -15min, 1h, 2h, 3h, 4h, 5h, 6h, 6h30min after begin of infusion | 
| Lab values (B-endorphin, fentanyl plasma Levels, potentially Adrenocorticotropic hormone (ACTH) / cortisol) |  | -15min, -10min, -5 min, 0 min, 15 min, 30 min, 45min, 1h, 1h 30min, 2h, 4h 30min, 4h 35min, 4h 40min, 4h 45min, 5h, 5h 30min, 6h, 6h 30min after begin of infusion | 
| pupillary dilation response |  | baseline and at 4.5h after begin of infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioid induced hyperalgesia, Fentanyl