Effect of the Kv7-channel Opener Flupirtine on the Excitability of Human Peripheral Myelinated Axons in Vivo

Study Overview
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Brief Summary
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Slow axonal Kv7 potassium channels are found along unmyelinated axons and at the nodes of Ranvier of myelinated axons in peripheral nerve. As such the pharmacological activation of Kv7 channels offers a potential means of reducing the excitability of peripheral axons. To determine whether this is the case for human peripheral myelinated axons, the effect of the Kv7 channel agonist flupirtine on the electrical excitability of A fibres was examined in both isolated segments of human sural nerve in vitro and in motor axons of the median nerve supplying abductor pollicus brevis in vivo. Axonal excitability was assessed in 21 human sural nerve fascicles in vitro and in 20 volunteers in vivo using threshold tracking in QTRAC (© Institute of Neurology, London, UK). Strength-duration time constant, rheobase current, relative refractory period (RRP), post spike superexcitability at 5 and 7 ms and threshold electrotonus over the 90 100 ms period were used as indices of electrical excitability. In addition, suppression of ectopic discharge in a model of upper limb ischaemia.

Official Title
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Evaluation of the Effect of the K+-Channel Opener Flupirtine on the Excitability of Human Peripheral Myelinated Axons in Vivo: a Randomised Controlled Trial

Conditions
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Pain, Axonal Change, Neuronal

Intervention / Treatment
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* Drug: flupirtine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: voluntarily age > 18 years old Exclusion Criteria: current use of medication (e.g. analgetics, antiepileptics, antidepressants, etc.) prevailing organic disease (e.g. diabetes, vascular or neurologic illness, etc.) previous physical trauma of the forearm (e.g. burning, surgery) primary organ failure pregnancy and lactation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo first<br>Volunteers receive placebo first and after a cross-over period of at least 7 days flupirtine second. On the days of the experiment outcome is taken as the change in excitability from Baseline (all measures before intervention) to a timepoint two hours after intervention | Drug: flupirtine<br>* Potassium channel opener (SNEPCO)<br>* Other names: brand names: Trancopal Dolo, Katadolon;|
| Experimental: Flupirtine first<br>Volunteers receive flupirtine first and after a cross-over period of at least 7 days placebo second. On the days of the experiment outcome is taken as the change in excitability from Baseline (all measures before intervention) to a timepoint two hours after intervention | Drug: flupirtine<br>* Potassium channel opener (SNEPCO)<br>* Other names: brand names: Trancopal Dolo, Katadolon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Axonal Excitability as assessed with QTrac | The primary outcome parameter of axonal excitability was the relative refractory period (RRP) as assessed with threshold tracking techniques. Strength-duration time constant, rheobase current, refractoriness determined at 2 and 2.5 ms, superexcitability at 7 ms and threshold electrotonus over the 90 100 ms period were used as secondary outcome measures. | Change of neuronal excitability from Baseline (before) to two hours after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ectopic Discharge | Further secondary outcome measures were power content for the surface EMG and the ranked summed scores for the McGill pain questionnaire. | Change of neuronal excitability from Baseline (before) to two hours after intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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human, neuropathy, axonal excitability, myelinated nerve, ectopic discharge, flupirtine