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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dr. Fleckenstein, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier:
NCT01450865
First received: October 10, 2011
Last updated: October 12, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Axonal Change, Neuronal
Pain
Drug: flupirtine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
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

Resource links provided by NLM:


Further study details as provided by Ludwig-Maximilians - University of Munich:

Primary Outcome Measures:
  • Axonal Excitability as assessed with QTrac [ Time Frame: Change of neuronal excitability from Baseline (before) to two hours after intervention ] [ Designated as safety issue: No ]
    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:
  • Ectopic Discharge [ Time Frame: Change of neuronal excitability from Baseline (before) to two hours after intervention ] [ Designated as safety issue: No ]
    Further secondary outcome measures were power content for the surface EMG and the ranked summed scores for the McGill pain questionnaire.


Enrollment: 20
Study Start Date: October 2009
Study Completion Date: August 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: flupirtine
Potassium channel opener (SNEPCO)
Other Name: brand names: Trancopal Dolo, Katadolon
Experimental: 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
Drug: flupirtine
Potassium channel opener (SNEPCO)
Other Name: brand names: Trancopal Dolo, Katadolon

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01450865

Locations
Germany
Multidisciplinary Pain Unit Department of Anaesthesiology University of Munich Pettenkoferstr. 8a
Munich, Bavaria, Germany, 80336
Sponsors and Collaborators
Ludwig-Maximilians - University of Munich
Investigators
Principal Investigator: Dominik Irnich, MD, PhD Multidisciplinary Pain Unit Department of Anaesthesiology University of Munich Pettenkoferstr. 8a D-80336 Munich
  More Information

No publications provided by Ludwig-Maximilians - University of Munich

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. Fleckenstein, Registrar, MD, Multidisciplinary Pain Centre, Department of Anaesthesiology, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier: NCT01450865     History of Changes
Other Study ID Numbers: EudraCT 2007-007314-10
Study First Received: October 10, 2011
Last Updated: October 12, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Germany: Ethics Commission

Keywords provided by Ludwig-Maximilians - University of Munich:
neuropathy
axonal excitability
myelinated nerve
human
ectopic discharge
flupirtine

Additional relevant MeSH terms:
Flupirtine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014