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

Ludwig Maximilian University of Munich

Status and phase: Completed; Phase 1

Conditions: Axonal Change, Neuronal; Pain

Treatments: Drug: flupirtine

Study type: Interventional

Funder types: Other

Identifiers

NCT01450865

EudraCT 2007-007314-10

Details and patient eligibility

About

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.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

20 participants in 2 patient groups

Placebo first

Experimental group

Description:

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

Treatment:

Drug: flupirtine

Flupirtine first

Experimental group

Description:

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

Treatment:

Drug: flupirtine