Trial record 4 of 4 for:    Stiff-Person Syndrome

Effects of Mutations of the Glycine Gene Associated With Hyperekplexia on Central Pain Processing

This study is currently recruiting participants.
Verified February 2014 by University Hospital Inselspital, Berne
Sponsor:
Information provided by:
University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier:
NCT01476514
First received: November 2, 2011
Last updated: February 6, 2014
Last verified: February 2014
  Purpose

Mutations in genes affecting pain transmission start to be known, the investigators are investigating a mutation in a glycine channel, which has an influence on pain modulation. Pain modulation is the ability of the central nervous system to enhance or diminish the sensation of pain. The investigators therefore will test patients and healthy volunteers with quantitative sensory tests, basically determining the point at which a stimulation just starts to induce pain. These tests are reliable and permit a direct comparison between healthy volunteers and patients with the affected glycine gene.


Condition Intervention
Hyperekplexia
Other: No intervention

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effects of Mutations of the Glycine Gene Associated With Hyperekplexia on Central Pain Processing

Resource links provided by NLM:


Further study details as provided by University Hospital Inselspital, Berne:

Primary Outcome Measures:
  • Pressure pain detection threshold measured in kPA, measured with electronic pressure algometer applied at the centre of the pulp of the 2nd toe [ Time Frame: Within 0 to 33 seconds after the beginning of the stimulation ] [ Designated as safety issue: No ]
    Pain detection thresholds will be measured with an electronic pressure algometer applied at the center of the pulp of the 2nd toe. The probe has a surface area of 1 cm2. The pressure is increased from 0 at a rate of 30kPa/s to a maximum pressure of 1000kPa. Pain detection threshold is defined as the point at which the pressure sensation turns to pain. The subjects are instructed to press a button when these points are reached. The algometer displays the pressure intensity at which the button is pressed.


Secondary Outcome Measures:
  • Electric pain reflex, as measured with electromyography from the biceps femoris and the rectus femoris muscles [ Time Frame: Within 50 to 150 ms after the beginning of stimulation ] [ Designated as safety issue: No ]
    Electromyographic (EMG) reflex responses to electrical stimulation will be recorded from the middle of the biceps femoris and the rectus femoris muscles (Ag/AgCl-electrodes). A 25 ms, train-of-five, 1 ms, square-wave impulse (perceived as a single stimulus), will be delivered. The current intensity will be increased from 1 mA in steps of 1 mA until: 1) a biceps femoris reflex with an amplitude exceeding 20 mV for at least 10 ms in the 50-150 ms post-stimulation interval will be detected (single stimulus reflex threshold); and 2) a pain sensation will be evoked (single stimulus pain threshold).

  • Heat and cold pain detection thresholds, as measured with a thermode in degrees Celsius [ Time Frame: Within 0 to 14 seconds after the beginning of the stimulation ] [ Designated as safety issue: No ]
    A thermode will be applied to the skin. The temperature of the thermode will be continuously increased from 30 ºC to a maximum of 50.5 ºC at a rate of 1.5 ºC/s. Pain detection threshold is defined as for pressure stimulation. The subjects are instructed to press a button when this point is reached. For cold stimulation, the temperature of the thermode will be continuously decreased from 30 ºC to a minimum of 0 ºC at a rate of 1.5 ºC/sec. Pain detection threshold is defined as for pressure stimulation. The subjects are instructed to press a button when this point is reached.

  • Ice water pain threshold of the hand as measured in seconds the hand was left in the water, measured with ice water container [ Time Frame: Within 0 to 2 minutes after the beginning of the stimulation ] [ Designated as safety issue: No ]
    The device consists of a container separated into an outer and an inner part by a mesh screen. The mesh screen prevents direct contact between the ice (placed in the outer part) and the hand of the subject (placed in the inner part). The water is regularly mixed to maintain the temperature in the inner part near to 0°C. The subject places his hand, wide open and to the wrist, into the inner part of the container. He is asked to keep it in the water until he feels an intolerable sensation of pain and is forced to remove his hand from the container, in any case for a maximum time of 2 min.

  • Pressure pain detection threshold measured in kPA, measured with electronic pressure algometer applied at the centre of the pulp of the 2nd toe [ Time Frame: At the end of the experiment, expected to be after 30 minutes on average ] [ Designated as safety issue: No ]
    Pain detection thresholds will be measured with an electronic pressure algometer applied at the center of the pulp of the 2nd toe. The probe has a surface area of 1 cm2. The pressure is increased from 0 at a rate of 30kPa/s to a maximum pressure of 1000kPa. Pain detection threshold is defined as the point at which the pressure sensation turns to pain. The subjects are instructed to press a button when these points are reached. The algometer displays the pressure intensity at which the button is pressed.


Estimated Enrollment: 68
Study Start Date: October 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1

In the setting of comparing patients with a genetic mutation and healthy volunteers blinding of the PI would demand a substantial increase in co-workers (i.e. recruitment, selection of age-and sex matched volunteers), reason why no blinding was chosen.

Affected patients will be compared to age and sex matched volunteers, recruited after completion of testing 23 hyperekplexia patients.

Other: No intervention
The testing will be the same for healthy volunteers and patients with a mutations in the glycine channel.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   7 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Hyperekplexia
  • GLRA1
  • GLRB
  • SCLA5
  • GPHN
  • Gephyrin
  • ARHGEF9

Exclusion Criteria

  • Age below 7 years
  • Pregnancy
  • Breast feeding
  • Ongoing medication
  • Cognitive impairment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01476514

Contacts
Contact: Pascal Vuilleumier, MD + 41 31 632 30 27 vuilleumierpasc@gmail.com

Locations
Switzerland
Dep. of Anesthesia and Pain medicine, Bern University Hospital Recruiting
Bern, Switzerland, 3010
Contact: Pascal H Vuilleumier, MD    +41 31 632 30 27    vuilleumierpasc@gmail.com   
Contact: Michele Curatolo, MD, PhD    +1 206 543 26 73    curatolo@uw.edu   
Principal Investigator: Pascal H Vuilleumier, MD         
Sub-Investigator: Raphael Fritsche         
Sponsors and Collaborators
University Hospital Inselspital, Berne
Investigators
Study Chair: Michele Curatolo, Prof. Dep. of Anesthesia and Pain medicine, Bern University Hospital
  More Information

Publications:
Responsible Party: Pascal H. Vuilleumier, MD, University Hospital Bern, Switzerland
ClinicalTrials.gov Identifier: NCT01476514     History of Changes
Other Study ID Numbers: 131/11, SPUM no. 33CM30_124117
Study First Received: November 2, 2011
Last Updated: February 6, 2014
Health Authority: Switzerland: Independent Local Research Ethic Commission (Ethikkommission)

Keywords provided by University Hospital Inselspital, Berne:
Hyperekplexia
Pain modulation
Glycine receptors
Hyperalgesia
Spinal inhibitory interneurons

Additional relevant MeSH terms:
Stiff-Person Syndrome
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Neuromuscular Diseases
Autoimmune Diseases
Immune System Diseases
Glycine
Glycine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014