Pain PerceptionNCT05440266
Electrical Intra-cutaneous Half-sine Stimulation for Optimized Preferential C-fiber Activation
A study testing Study Intervention: 25 ms half-sine wave stimulation in people with Pain Perception and Secondary Hyperalgesia, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Pain Perception, Secondary Hyperalgesia
- What is being tested?
- Study Intervention: 25 ms half-sine wave stimulation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteSwitzerland
- Study dates
- 20 May 2022to 25 Nov 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Department of Anaesthesiology, University Hospital of Basel (USB)
Basel, 4031
About this study
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)
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.
Read the 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)
- Conditions
- Pain Perception, Secondary Hyperalgesia
- Being tested
- Study Intervention: 25 ms half-sine wave stimulation, Control Intervention: 500 µs rectangular shaped stimulation
- 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)
- Medical subject headings
- Hyperalgesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Study Intervention: 25 ms half-sine wave stimulationDiagnostic test
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.
Control Intervention: 500 µs rectangular shaped stimulationDiagnostic test
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.
| Study group | Role | What they receive |
|---|---|---|
| First: half-sine wave stimulation; Second: rectangular shaped stimulation | Active comparator | 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. Receives: Diagnostic Test: Study Intervention: 25 ms half-sine wave stimulation; Diagnostic Test: Control Intervention: 500 µs rectangular shaped stimulation |
| First: rectangular shaped stimulation; Second: half-sine wave stimulation | Active comparator | 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. Receives: Diagnostic Test: Study Intervention: 25 ms half-sine wave stimulation; Diagnostic Test: Control Intervention: 500 µs rectangular shaped stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 65 minutes from start of stimulation until stop of stimulation
Secondary outcomes (3)
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.
Measured: approx. 65 minutes at each intervention day (first appointment and second appointment)
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.
Measured: approx. 65 minutes at each intervention (first appointment and second appointment)
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).
Measured: approx. 65 minutes at each intervention day (first appointment and second appointment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2022
- Study start20 May 2022
- Primary completion25 Nov 2022
- Study completion25 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pain PerceptionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- randomized, crossover, single-blinded experimental proof of concept investigation in healthy volunteers
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tobias Schneider, Dr. med., Principal investigator, Department of Anaesthesiology, University Hospital of Basel (USB)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05440266
- Sponsor's protocol ID
- 2022-00682; am22Schneider2
- Status last verified
- Nov 2023
- First submitted
- 21 Jun 2022
- Last updated
- 28 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05440266
- Acronym / sponsor ID
- 2022-00682; am22Schneider2
- Conditions
- Pain Perception, Secondary Hyperalgesia
- Keywords
- C-fiber activation, evoked pain, hyperalgesia, allodynia, half-sine stimulation, 25ms HS stimulation, pain perception, nociceptors
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 20 May 2022 (actual)
- Primary completion
- 25 Nov 2022 (actual)
- Study completion
- 25 Nov 2022 (actual)
- First posted
- 30 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- randomized, crossover, single-blinded experimental proof of concept investigation in healthy volunteers
| Arm | Type | Receives |
|---|---|---|
| First: half-sine wave stimulation; Second: rectangular shaped stimulation | Active comparator | Diagnostic Test: Study Intervention: 25 ms half-sine wave stimulation, Diagnostic Test: Control Intervention: 500 µs rectangular shaped stimulationFirst 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: rectangular shaped stimulation; Second: half-sine wave stimulation | Active comparator | Diagnostic Test: Study Intervention: 25 ms half-sine wave stimulation, Diagnostic Test: Control Intervention: 500 µs rectangular shaped stimulationFirst 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Study Intervention: 25 ms half-sine wave stimulationPart 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. | Diagnostic test | First: half-sine wave stimulation; Second: rectangular shaped stimulation, First: rectangular shaped stimulation; Second: half-sine wave stimulation |
| Control Intervention: 500 µs rectangular shaped stimulationPart 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. | Diagnostic test | First: half-sine wave stimulation; Second: rectangular shaped stimulation, First: rectangular shaped stimulation; Second: half-sine wave stimulation |
Primary outcome
Secondary hyperalgesia measured by the area under the curve (AUCHyperHS)
Time frame: 65 minutes from start of stimulation until stop of stimulation
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
3 secondary outcomes
Number of pulses needed to reach 25% of the final extent of the flare response
Time frame: approx. 65 minutes at each intervention day (first appointment and second appointment)
Needed time (in minutes) to generate 50% of the final extent of secondary hyperalgesia.
Time frame: approx. 65 minutes at each intervention (first appointment and second appointment)
Current intensity needed to reach same pain level (NRS 6)
Time frame: approx. 65 minutes at each intervention day (first appointment and second appointment)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tobias Schneider, Dr. med. principal investigator
Department of Anaesthesiology, University Hospital of Basel (USB)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Study Intervention: 25 ms half-sine wave stimulation in people with Pain Perception and Secondary Hyperalgesia, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Secondary hyperalgesia measured by the area under the curve (AUCHyperHS) (time frame: 65 minutes from start of stimulation until stop of stimulation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2023.