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

NCT01450865 | Completed Phase 1 DMC

• 1 other identifier: EudraCT 2007-007314-10
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Keywords

neuropathy; axonal excitability; myelinated nerve; human; ectopic discharge; flupirtine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Ectopic Discharge

  Change of neuronal excitability from Baseline (before) to two hours after intervention

Study Arms (2)

Placebo first

EXPERIMENTAL

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

Flupirtine first

EXPERIMENTAL

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

Interventions

flupirtine DRUG

Potassium channel opener (SNEPCO)

Also known as: brand names: Trancopal Dolo, Katadolon

Flupirtine first; Placebo first

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• voluntarily
• age \> 18 years old

You may not qualify if:

• 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

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead

Study Sites (1)

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

Munich, Bavaria, 80336, Germany

Location

Related Publications (1)

• 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.

  PMID: 23394517 RESULT

Related Links

• Homepage of the respective Journal

MeSH Terms

Conditions

Pain

Interventions

flupirtine

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Dominik Irnich, MD, PhD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Registrar, MD, Multidisciplinary Pain Centre, Department of Anaesthesiology

Study Record Dates

• First Submitted: October 10, 2011
• First Posted: October 12, 2011
• Study Start: October 1, 2009
• Primary Completion: July 1, 2010
• Study Completion: August 1, 2010
• Last Updated: January 13, 2015

Record last verified: 2015-01

Locations

DE (1)