Pharmacological Modulation of Peripheral Nerve Excitability

Pharmacological Modulation of Peripheral Nerve Excitability - Measurement With the Human Perception Threshold Tracking Method

The present project is a human experimental study. The aim is to assess the pharmacologically modulated excitability of peripheral sensory nerves with a human experimental model.

The study measures the excitability of peripheral sensory nerves before and after application of different topical drugs (lidocaine (5%), phenytoin (10%),mepyramine (2%) and placebo).

Study Overview

• Status: Completed
• Conditions: Peripheral Neuropathy
• Intervention / Treatment: Drug: Topical lidocaine 5%; Drug: Topical Phenytoin 10%; Drug: Topical Mepyramine 2%; Other: Topical Placebo

Detailed Description

Design and method Study design The study is a randomized, double-blinded, placebo-controlled study. To minimize the risk of bias and achieve balance in the allocation of participants and application of creams, block randomization is used. To ensure double blinding, 1-2 colleagues from Center for Neuroplasticity and Pain (CNAP), who is not otherwise involved in the project, will keep the randomization list in a secure room.

Study procedure and experimental test The PTT model will be used to measure the excitability of peripheral sensory afferents. PTT will be measured before and after topical drug application at four distinct areas - two at each side of the volar site of the forearms.

In total four topical creams will be used in the study. One cream containing placebo, one with lidocaine (5%), one with phenytoin (10%) and one with mepyramine (2%).

The study consists of one session lasting 3-4 hrs. The study will include 20 healthy volunteers.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark
    • Center For Neuroplasticity and Pain

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Men and Women age > 18 years
• Understand and speak Danish
• No medication besides contraceptives

Exclusion Criteria:

• Pregnancy or lactating women
• Drug addiction (use of cannabis, opioids, or other drugs)
• Use of pain killers, alcohol, or nicotine within the last 24 hours before study start
• Any other medical treatment (e.g., antidepressants, anticonvulsants)
• History of peripheral or chronic pain conditions / neuropathy
• Skin diseases
• Scars and/or tattoos at the volar site of the forearm
• Previous traumatic experience of an electrical accident
• Application of moisturizing lotion of the volar site of the forearms (24 hours before study start)
• Participation in any other research projects/studies 7 days before study start
• Known allergy/intolerance to lidocaine/phenytoin/mepyramine
• Lack of ability to cooperate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pharmacological modulation with lidocaine 5%; Experimental investigation of pharmacological modulation of peripheral nerve excitability, which is measured with the human perception threshold tracking method. With this method neurophysiological mechanisms of sensory afferents can be investigated	Drug: Topical lidocaine 5%; Drug is used to pharmacologically modulate peripheral sensory afferents
Active Comparator: Pharmacological modulation with Phenytoin 10%; Experimental investigation of pharmacological modulation of peripheral nerve excitability, which is measured with the human perception threshold tracking method. With this method neurophysiological mechanisms of sensory afferents can be investigated	Drug: Topical Phenytoin 10%; Drug is used to pharmacologically modulate peripheral sensory afferents
Active Comparator: Pharmacological modulation with Mepyramine 2%; Experimental investigation of pharmacological modulation of peripheral nerve excitability, which is measured with the human perception threshold tracking method. With this method neurophysiological mechanisms of sensory afferents can be investigated	Drug: Topical Mepyramine 2%; Drug is used to pharmacologically modulate peripheral sensory afferents
Placebo Comparator: Control; Experimental investigation of pharmacological modulation of peripheral nerve excitability, which is measured with the human perception threshold tracking method. With this method neurophysiological mechanisms of sensory afferents can be investigated	Other: Topical Placebo; Drug is used as control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PTT-value	Primary outcome measures are changes in the PTT-value (registered as mA) before and after application with topical pharmaceutical drugs.	1 hour after application of cream

Collaborators and Investigators

• Sponsor: Aalborg University
• Investigators: Study Director: Trine Andresen, Post.Doc, Center For Neuroplasticity and Pain

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2024
• Primary Completion (Actual): December 2, 2024
• Study Completion (Actual): December 11, 2024

Study Registration Dates

• First Submitted: February 27, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 28, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Topical treatment; Small fiber excitability; Perception Threshold Tracking Method
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Sleep Aids, Pharmaceutical; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Hypnotics and Sedatives; Anti-Allergic Agents; Anticonvulsants; Cytochrome P-450 Enzyme Inducers; Histamine H1 Antagonists; Cytochrome P-450 CYP1A2 Inducers; Lidocaine; Phenytoin; Pyrilamine
• Other Study ID Numbers: N-20230071

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No