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

Phase 1

Completed

• Conditions: Pain; Axonal Change, Neuronal
• Interventions: Drug: flupirtine

• Registration Number: NCT01450865
• Lead Sponsor: Ludwig-Maximilians - University of Munich

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-10
• Primary Completion: 2010-07
• Study Completion: 2010-08
• Study First Submitted: 2011-10-10
• Study First Submitted QC: 2011-10-10
• Study First Posted: 2011-10-12
• Status Verified: 2015-01
• Last Update Submitted: 2015-01-12
• Last Update Posted: 2015-01-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo first	flupirtine	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
Flupirtine first	flupirtine	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

Primary Outcome Measures

Name	Time	Method
Axonal Excitability as assessed with QTrac	Change of neuronal excitability from Baseline (before) to two hours after intervention	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Multidisciplinary Pain Unit Department of Anaesthesiology University of Munich Pettenkoferstr. 8a; 🇩🇪 Munich, Bavaria, Germany