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

NCT01476514 | Terminated

• 2 other identifiers: 131/11SPUM no. 33CM30_124117
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hyperekplexia

Keywords

Hyperekplexia; Pain modulation; Glycine receptors; Hyperalgesia; Spinal inhibitory interneurons

Outcome Measures

Primary Outcomes (1)

• Pressure pain detection threshold measured in kPA, measured with electronic pressure algometer applied at the centre of the pulp of the 2nd toe

  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.

  Within 0 to 33 seconds after the beginning of the stimulation

Secondary Outcomes (4)

• Electric pain reflex, as measured with electromyography from the biceps femoris and the rectus femoris muscles

  Within 50 to 150 ms after the beginning of stimulation

• Heat and cold pain detection thresholds, as measured with a thermode in degrees Celsius

  Within 0 to 14 seconds after the beginning of the stimulation

• Ice water pain threshold of the hand as measured in seconds the hand was left in the water, measured with ice water container

  Within 0 to 2 minutes after the beginning of the stimulation

• Pressure pain detection threshold measured in kPA, measured with electronic pressure algometer applied at the centre of the pulp of the 2nd toe

  At the end of the experiment, expected to be after 30 minutes on average

Study Arms (1)

1

EXPERIMENTAL

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

Interventions

No intervention OTHER

The testing will be the same for healthy volunteers and patients with a mutations in the glycine channel.

1

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Age below 7 years
• Pregnancy
• Breast feeding
• Ongoing medication
• Cognitive impairment

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Dep. of Anesthesia and Pain medicine, Bern University Hospital

Bern, Canton of Bern, 3010, Switzerland

Location

Related Publications (4)

• Zhou L, Chillag KL, Nigro MA. Hyperekplexia: a treatable neurogenetic disease. Brain Dev. 2002 Oct;24(7):669-74. doi: 10.1016/s0387-7604(02)00095-5.

  PMID: 12427512 BACKGROUND

• Andermann F, Keene DL, Andermann E, Quesney LF. Startle disease or hyperekplexia: further delineation of the syndrome. Brain. 1980 Dec;103(4):985-97. doi: 10.1093/brain/103.4.985.

  PMID: 6777025 BACKGROUND

• Praveen V, Patole SK, Whitehall JS. Hyperekplexia in neonates. Postgrad Med J. 2001 Sep;77(911):570-2. doi: 10.1136/pmj.77.911.570.

  PMID: 11524514 BACKGROUND

• Muller F, Heinke B, Sandkuhler J. Reduction of glycine receptor-mediated miniature inhibitory postsynaptic currents in rat spinal lamina I neurons after peripheral inflammation. Neuroscience. 2003;122(3):799-805. doi: 10.1016/j.neuroscience.2003.07.009.

  PMID: 14622922 BACKGROUND

MeSH Terms

Conditions

Hyperekplexia; Hyperalgesia

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases; Somatosensory Disorders; Sensation Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Michele Curatolo, Prof.

  Dep. of Anesthesia and Pain medicine, Bern University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 2, 2011
• First Posted: November 22, 2011
• Study Start: October 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: September 4, 2014

Record last verified: 2014-09

Locations

CH (1)