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Electrical Intra-cutaneous Half-sine Stimulation for Optimized Preferential C-fiber Activation

Primary Purpose

Pain Perception, Secondary Hyperalgesia

Status
Recruiting
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
Study Intervention: 25 ms half-sine wave stimulation
Control Intervention: 500 µs rectangular shaped stimulation
Sponsored by
University Hospital, Basel, Switzerland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Pain Perception focused on measuring C-fiber activation, evoked pain, hyperalgesia, allodynia, half-sine stimulation, 25ms HS stimulation, pain perception, nociceptors, rectangular current stimulation, electrical pain model, numeric rating scale (NRS)

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy adults (18 - 65 years old, American Society of Anaesthesiologists (ASA) I or II)
  • BMI between 18.5 until 25 kg/m2
  • Able to understand the study and the NRS scale
  • Able to give informed consent

Exclusion Criteria:

  • Regular intake of medications or drugs potentially interfering with pain sensation (analgesics, opioids, antihistamines, calcium and potassium channel blockers, serotonin / noradrenaline reuptake inhibitors, corticosteroids)
  • Neuropathy
  • Chronic pain
  • Neuromuscular disease
  • Dermatological disease as Atopic Dermatitis
  • Psychiatric disease
  • Pregnancy / Lactation

Sites / Locations

  • Department of Anaesthesiology, University Hospital of Basel (USB)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

First: half-sine wave stimulation; Second: rectangular shaped stimulation

First: rectangular shaped stimulation; Second: half-sine wave stimulation

Arm Description

First appointment: Intracutaneously applied electrical 25 ms half-sine wave stimulation with 2 Hz frequency. Second appointment: Intracutaneously applied electrical 500 µs rectangular shaped stimulation with 2 Hz frequency.

First appointment: Intracutaneously applied electrical 500 µs rectangular shaped stimulation with 2 Hz frequency. Second appointment: Intracutaneously applied electrical 25 ms half-sine wave stimulation with 2 Hz frequency.

Outcomes

Primary Outcome Measures

Secondary hyperalgesia measured by the area under the curve (AUCHyperHS)
Difference between the AUC of secondary hyperalgesia during 25ms half-sine wave stimulation (AUCHyperHS) at pain level NRS 6 for 65 minutes and the AUC of secondary hyperalgesia measured during 500µs rectangular shaped stimulation (AUCHyperRect) at pain level NRS 6 for 65 minutes

Secondary Outcome Measures

Number of pulses needed to reach 25% of the final extent of the flare response
The number of pulses needed to reach 25% of the final extent of the flare response (measured with a laser Doppler line scan while applying 214 impulses in total) at detection and pain threshold and at pain level NRS 3.
Needed time (in minutes) to generate 50% of the final extent of secondary hyperalgesia.
Difference between the needed time (in minutes) to generate 50% of the final extent of secondary hyperalgesia during 25ms half-sine wave stimulation and during 500µs rectangular shaped stimulation.
Current intensity needed to reach same pain level (NRS 6)
Difference of the amount of current intensity needed to reach same pain level (NRS 6) after adaption during the first 15 minutes of stimulation between half-sine and rectangular currents (0 = no pain and 10 = maximum tolerable pain).

Full Information

First Posted
June 21, 2022
Last Updated
June 28, 2022
Sponsor
University Hospital, Basel, Switzerland
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1. Study Identification

Unique Protocol Identification Number
NCT05440266
Brief Title
Electrical Intra-cutaneous Half-sine Stimulation for Optimized Preferential C-fiber Activation
Official Title
Electrical Intra-cutaneous Half-sine Stimulation for Optimized Preferential C-fiber Activation in an Established Model of Evoked Pain, Hyperalgesia and Allodynia in Humans (25ms HS Stimulation)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 20, 2022 (Actual)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This exploratory study is to improve an established pain model by a new stimulation profile that allows preferential activation of C fibers that are of main clinical interest in chronic pain and also to generate a stable secondary hyperalgesia, which is of particular interest in the actual research of acute and chronic pain. It is to investigate if the specific activation of afferent sensory fibers and expected lower current intensities makes it more comfortable for the participant as motor neuron activation is much less pronounced at low current intensities. Therefore it compares the area under the curve (AUC) of hyperalgesia during electrical, intracutaneous 25 ms half-sine wave stimulation at a pain level of the numeric rating scale (NRS) of 6 out of 10 for 65 minutes compared to 500 µs rectangular pulses.
Detailed Description
Nociceptors in the epidermis are responsible for peripheral pain perception. Mechanical, thermal as well as chemical stimuli can trigger action potentials in nociceptors and thereby pain. Regarding pain, polymodal and "silent" C-fibers are of special interest. Slower depolarisation via sine and half-sine currents preferentially stimulate C-fibers compared to rectangular shaped currents. This study is to compare the development of central sensitization comparing the half-sine wave and the rectangular stimulation, hypothesizing that preferential C fiber stimulation through half-sine currents facilitate the development of secondary hyperalgesia. This exploratory study is to improve an established pain model by a new stimulation profile that allows preferential activation of C fibers that are of main clinical interest in chronic pain and also to generate a stable secondary hyperalgesia, which is of particular interest in the actual research of acute and chronic pain. It is to investigate if the specific activation of afferent sensory fibers and expected lower current intensities makes it more comfortable for the participant as motor neuron activation is much less pronounced at low current intensities. Therefore it compares the area under the curve (AUC) of hyperalgesia during electrical, intracutaneous 25 ms half-sine wave stimulation at a pain level of the numeric rating scale (NRS) of 6 out of 10 for 65 minutes compared to 500 µs rectangular pulses. Every volunteer will have two appointments. There will be a "washout" period of at least two weeks between the two appointments. On each day two microdialysis catheters containing internally a stainless steel wire will be inserted intracutaneously on the volar surface of the adominant forearm for a length of approximately 10 mm and at a distance of 5 mm. Before insertion, the catheters are filled with 0.9% saline and after insertion a continuous flow of 0.4 μl/min will be ensured by a syringe pump (Perfusor®) to facilitate conduction and to protect the tissue from potential local pH changes by the direct current. Alternating polarity of the both pulses is used to ensure charge-balanced stimulation. It is randomly assigned which current form is applied on the first and on the second trial. Subsequently, the stainless steel wire serving as electrodes of the current generator (for 25 ms half-sine stimulation the Digitimer DS5; Digitimer Ltd, Hertfordshire, United Kingdom; and for 500 µs rectangular stimulation the Digitimer DS7A; Digitimer Ltd, Hertfordshire, United Kingdom) are connected. The rectangular pulses are generated by the Digitimer DS7A, which works in combination with a pulse generator (PG 1, Rimkus Medizintechnik, Parsdorf, Germany)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain Perception, Secondary Hyperalgesia
Keywords
C-fiber activation, evoked pain, hyperalgesia, allodynia, half-sine stimulation, 25ms HS stimulation, pain perception, nociceptors, rectangular current stimulation, electrical pain model, numeric rating scale (NRS)

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
randomized, crossover, single-blinded experimental proof of concept investigation in healthy volunteers
Masking
Participant
Masking Description
Only the study team will know which stimulation will be applied on which intervention. The participant won't be informed about the applied stimulation type.
Allocation
Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
First: half-sine wave stimulation; Second: rectangular shaped stimulation
Arm Type
Active Comparator
Arm Description
First appointment: Intracutaneously applied electrical 25 ms half-sine wave stimulation with 2 Hz frequency. Second appointment: Intracutaneously applied electrical 500 µs rectangular shaped stimulation with 2 Hz frequency.
Arm Title
First: rectangular shaped stimulation; Second: half-sine wave stimulation
Arm Type
Active Comparator
Arm Description
First appointment: Intracutaneously applied electrical 500 µs rectangular shaped stimulation with 2 Hz frequency. Second appointment: Intracutaneously applied electrical 25 ms half-sine wave stimulation with 2 Hz frequency.
Intervention Type
Diagnostic Test
Intervention Name(s)
Study Intervention: 25 ms half-sine wave stimulation
Intervention Description
Part I: Threshold detection and Flare response: 6 pulses of 25 ms half-sine are given at 2 Hz each, increasing current intensity (mA) until detection threshold, pain threshold and pain level (3 out of 10 NRS) are reached. Determined intensity values reapplied during 214 impulses. Line scan to visualize changes in local skin blood flow done. Part II: Hyperalgesia, Allodynia, Pain and flare response of 65 minutes. Baseline assessment of local skin perfusion and spatial extent of allodynia by using cotton swab and pinprick hyperalgesia. Current intensity is reapplied, adjusted until pain level of 6 reached. After 5 minutes axon reflex flare, allodynia and secondary hyperalgesia are measured and repeated proximal every 10 minutes with last measurement after 65 minutes. In first 15 minutes current intensity is adapted to maintain NRS level of 6. During this 65 minutes' period, 25 ms half-sine is administered continuously.
Intervention Type
Diagnostic Test
Intervention Name(s)
Control Intervention: 500 µs rectangular shaped stimulation
Intervention Description
Part I: Threshold detection and Flare response: 6 pulses of 500 µs rectangular shaped stimulation are given at 2 Hz each, increasing current intensity (mA) until detection threshold, pain threshold and pain level (3 out of 10 NRS) are reached. Determined intensity values reapplied during 214 impulses. Line scan to visualize changes in local skin blood flow done. Part II: Hyperalgesia, Allodynia, Pain and flare response of 65 minutes. Baseline assessment of local skin perfusion and spatial extent of allodynia by using cotton swab and pinprick hyperalgesia. Current intensity is reapplied, adjusted until pain level of 6 reached. After 5 minutes axon reflex flare, allodynia and secondary hyperalgesia are measured and repeated proximal every 10 minutes with last measurement after 65 minutes. In first 15 minutes current intensity is adapted to maintain NRS level of 6. During this 65 minutes' period, 500 µs rectangular shaped stimulation is administered continuously.
Primary Outcome Measure Information:
Title
Secondary hyperalgesia measured by the area under the curve (AUCHyperHS)
Description
Difference between the AUC of secondary hyperalgesia during 25ms half-sine wave stimulation (AUCHyperHS) at pain level NRS 6 for 65 minutes and the AUC of secondary hyperalgesia measured during 500µs rectangular shaped stimulation (AUCHyperRect) at pain level NRS 6 for 65 minutes
Time Frame
65 minutes from start of stimulation until stop of stimulation
Secondary Outcome Measure Information:
Title
Number of pulses needed to reach 25% of the final extent of the flare response
Description
The number of pulses needed to reach 25% of the final extent of the flare response (measured with a laser Doppler line scan while applying 214 impulses in total) at detection and pain threshold and at pain level NRS 3.
Time Frame
approx. 65 minutes at each intervention day (first appointment and second appointment)
Title
Needed time (in minutes) to generate 50% of the final extent of secondary hyperalgesia.
Description
Difference between the needed time (in minutes) to generate 50% of the final extent of secondary hyperalgesia during 25ms half-sine wave stimulation and during 500µs rectangular shaped stimulation.
Time Frame
approx. 65 minutes at each intervention (first appointment and second appointment)
Title
Current intensity needed to reach same pain level (NRS 6)
Description
Difference of the amount of current intensity needed to reach same pain level (NRS 6) after adaption during the first 15 minutes of stimulation between half-sine and rectangular currents (0 = no pain and 10 = maximum tolerable pain).
Time Frame
approx. 65 minutes at each intervention day (first appointment and second appointment)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy adults (18 - 65 years old, American Society of Anaesthesiologists (ASA) I or II) BMI between 18.5 until 25 kg/m2 Able to understand the study and the NRS scale Able to give informed consent Exclusion Criteria: Regular intake of medications or drugs potentially interfering with pain sensation (analgesics, opioids, antihistamines, calcium and potassium channel blockers, serotonin / noradrenaline reuptake inhibitors, corticosteroids) Neuropathy Chronic pain Neuromuscular disease Dermatological disease as Atopic Dermatitis Psychiatric disease Pregnancy / Lactation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tobias Schneider, Dr. med.
Phone
+41 61 328 64 96
Email
tobias.schneider@usb.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Wilhelm Ruppen, Prof. Dr. med.
Phone
+41 61 328 64 96
Email
wilhelm.ruppen@usb.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tobias Schneider, Dr. med.
Organizational Affiliation
Department of Anaesthesiology, University Hospital of Basel (USB)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Anaesthesiology, University Hospital of Basel (USB)
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tobias Schneider, Dr. med.
Phone
+41 61 328 64 96
Email
tobias.schneider@usb.ch
First Name & Middle Initial & Last Name & Degree
Tobias Schneider, Dr. med.
First Name & Middle Initial & Last Name & Degree
Luana Daneffel
First Name & Middle Initial & Last Name & Degree
Martin Schmelz, Prof. Dr. med.
First Name & Middle Initial & Last Name & Degree
Roman Rukwied, Prof. Dr. med.

12. IPD Sharing Statement

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Electrical Intra-cutaneous Half-sine Stimulation for Optimized Preferential C-fiber Activation

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