Clinical trial NCT01450865: Effect of the Kv7-channel Opener Flupirtine on the Excitability of Human Peripheral Myelinated Axons in Vivo
Official title: Evaluation of the Effect of the K+-Channel Opener Flupirtine on the Excitability of Human Peripheral Myelinated Axons in Vivo: a Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Axonal Change, Neuronal
Pain
Keywords: neuropathy
axonal excitability
myelinated nerve
human
ectopic discharge
flupirtine
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
First posted: 2011-10-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Axonal Excitability as assessed with QTrac
timeFrame: Change of neuronal excitability from Baseline (before) to two hours after intervention
Secondary outcomes:
measure: Ectopic Discharge
timeFrame: Change of neuronal excitability from Baseline (before) to two hours after intervention
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Multidisciplinary Pain Unit Department of Anaesthesiology University of Munich Pettenkoferstr. 8a
state: Bavaria
Study officials:
affiliation: Multidisciplinary Pain Unit Department of Anaesthesiology University of Munich Pettenkoferstr. 8a D-80336 Munich
name: Dominik Irnich, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fleckenstein J, Sittl R, Averbeck B, Lang PM, Irnich D, Carr RW. Activation of axonal Kv7 channels in human peripheral nerve by flupirtine but not placebo - therapeutic potential for peripheral neuropathies: results of a randomised controlled trial. J Transl Med. 2013 Feb 8;11:34. doi: 10.1186/1479-5876-11-34.