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

NCT ID: NCT01450865

Last Updated: 2015-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2010-08-31

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.

Conditions

Axonal Change, Neuronal; Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo first

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

Group Type: EXPERIMENTAL

flupirtine

Intervention Type: DRUG

Potassium channel opener (SNEPCO)

Flupirtine first

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

Group Type: EXPERIMENTAL

flupirtine

Intervention Type: DRUG

Potassium channel opener (SNEPCO)

Interventions

flupirtine

Potassium channel opener (SNEPCO)

Intervention Type: DRUG

Other Intervention Names

brand names: Trancopal Dolo, Katadolon

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role: lead

Responsible Party

Dr. Johannes Fleckenstein

Registrar, MD, Multidisciplinary Pain Centre, Department of Anaesthesiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dominik Irnich, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Multidisciplinary Pain Unit Department of Anaesthesiology University of Munich Pettenkoferstr. 8a D-80336 Munich

Locations

Multidisciplinary Pain Unit Department of Anaesthesiology University of Munich Pettenkoferstr. 8a

Munich, Bavaria, Germany

Countries

Germany

References

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.

Reference Type: RESULT

PMID: 23394517 (View on PubMed)

Related Links

http://www.translational-medicine.com/content/11/1/34

Homepage of the respective Journal

Other Identifiers

EudraCT 2007-007314-10

Identifier Type: -

Identifier Source: org_study_id