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Painful Channelopathies Study (PCS)

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ClinicalTrials.gov Identifier: NCT02696746
Recruitment Status : Recruiting
First Posted : March 2, 2016
Last Update Posted : February 22, 2019
Sponsor:
Collaborators:
University of Oxford
Neuroscience Technologies S.L.P
Information provided by (Responsible Party):
King's College London

Brief Summary:

To understand the pathophysiological basis of heritable pain syndromes. This will consist of a number of components:

  • Determine the genetic basis for heritable pain syndromes.
  • Investigate the pain symptoms, psychological co-morbidity and quality of life in patients with heritable pain syndromes.
  • Use quantitative sensory testing to investigate abnormalities in sensory processing.
  • Use imaging modalities to investigate the neural correlates of pain perception in heritable channelopathies.
  • In select patients to perform skin biopsy to determine if there has been any damage to C-fibres.
  • To perform skin biopsy in order to culture fibroblasts and neural crest stem cells for future studies into the molecular basis of altered pain perception.
  • To use neurophysiological tests, the axon reflex, and conditioning challenges to determine how peripheral nerves, in heritable channelopathies and unusual pain syndromes, have been altered.
  • Microneurographic recordings for directly detecting the function of pain fibres in peripheral nerves. Knowledge gained from the study will be used to aid the further development of genetic testing and specific pain questionnaires for the diagnosis of heritable pain syndromes secondary to channelopathies.
  • Ultimately better knowledge of underlying pathophysiology in these heritable pain conditions may inform the development of novel treatments.

Condition or disease Intervention/treatment
Erythromelalgia Pain Insensitivity, Congenital Hereditary Sensory and Autonomic Neuropathies Chronic Pain Other: Observation

  Show Detailed Description

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Painful Channelopathies Study
Study Start Date : February 2012
Estimated Primary Completion Date : June 2019


Group/Cohort Intervention/treatment
Pain related conditions
Subjects with painful or painless conditions (observational study, no interventions)
Other: Observation
No intervention




Primary Outcome Measures :
  1. Pain score [ Time Frame: Day 7 ]
    Seven days pain diary of 4 or above. Patients will have 7-days pain diaries with a numeric rating scale from 0 to 10.


Secondary Outcome Measures :
  1. Age [ Time Frame: Day 1 ]
    Number of years

  2. Gender [ Time Frame: Day 1 ]
    Chromosome gender (male/female)

  3. Ethnicity [ Time Frame: Day 1 ]
    Ethnic group

  4. Detailed medical history [ Time Frame: Day 1 ]
    Number and name of medications that were taken previously by the patient

  5. Pain related anxiety [ Time Frame: Day 1 ]
    Patients will answer the Pain Anxiety Symptoms Scale (PASS-20)

  6. Measures of quality of life [ Time Frame: Day 1 ]
    Patients will answer the 36-Item Short Form Survey -quality of life questionnaire-

  7. Measures of sleep interference [ Time Frame: Day 1 ]
    Sleep quality is assessed through the use of questionnaires

  8. Nerve Conduction Studies [ Time Frame: Day 1 ]
    Neurophysiology will be conducted to assess nerve integrity. Amplitude will be measured in microvolts.

  9. Nerve Conduction Studies [ Time Frame: Day 1 ]
    Neurophysiology will be conducted to assess nerve integrity. Latency will be measured in milliseconds.

  10. Microneurography Studies [ Time Frame: Day 1 ]
    This is a minimally invasive technique in which the activity of single nerve fibre is recorded from peripheral nerves and is for directly detecting the function of pain fibres in peripheral nerves in humans.

  11. Sensory Thermal Thresholds [ Time Frame: Day 1 ]
    Thermal thresholds will be measured in degrees centigrade

  12. Sensory Mechanical Detection Thresholds [ Time Frame: Day 1 ]
    Mechanical Detection Thresholds will be measured in millinewtons

  13. Intra-Epidermal Nerve Fibre density [ Time Frame: Day 1 ]
    Measurement of nerve fibres in the skin of patients (taken depending of the pain related area)

  14. Skin biopsy [ Time Frame: Day 1 ]
    Collection and culture of fibroblasts and neural crest stem cells for assessing differences in the rheobase measured in amperes.

  15. Axon reflex measurement [ Time Frame: Day 1 ]
    Application of agents such as histamine via iontophoresis which will stimulate the peripheral nerve endings of C fibres inducing a vasodilatation, which is visible as a flare response of the skin (area in square centimeters with flare).

  16. Functional Magnetic Resonance Imaging [ Time Frame: Day 30 ]
    Brain activity related to the pain condition

  17. Blood samples - DNA [ Time Frame: Within 6 months of visit ]
    Blood samples coupled with detailed phenotype data will investigate potential gene associations in the development of painful or painless conditions.


Biospecimen Retention:   Samples With DNA
  1. The investigators will collect blood samples (30mls) from each subject, which will be stored at -800C in a locked freezer. They will sequence known genes associated with painful channelopathies: SCN9a and TRPA1. They will store DNA in order that it is possible that other candidate genes associated with pain can be tested.
  2. 3mm skin punch biopsies performed 10 cm above lateral malleolus for 2 different purposes:

    • Nerve fibre density measurement
    • Fibroblasts cultures as these represent a useful tool in the future as a source of cells the phenotype of which can be modulated for instance to generate induced pluripotent stem cells


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients and family members affected by chanelopathic pain related conditions.
Criteria

Inclusion Criteria:

  • Patients who are ≥16 years of age who have a set of symptoms that resemble those seen on Paroxysmal Extreme Pain Disorder, Familial Episodic Pain Syndrome or Erythromelalgia.
  • Patients already with the diagnosis of Paroxysmal Extreme Pain Disorder or Familial Episodic Pain Syndrome or Erythromelalgia.
  • Patients with reduced pain sensibility.
  • First degree relatives of patients who meet diagnostic criteria for Paroxysmal Extreme Pain Disorder, Familial Episodic Pain Syndrome, Erythromelalgia or inability to experience pain.
  • Patients who do not fulfill any of the exclusion criteria.

Exclusion Criteria:

  • Pregnant subjects.
  • Subjects with insufficient command of English to obtain consent from or to complete the study questionnaires.
  • Subjects with insufficient mental capacity to obtain consent from or to complete the study questionnaires.
  • Subjects with concurrent severe psychological or psychiatric disorders, specially those patients with severe claustrophobia.
  • Patients with moderate to severe pain arising as a consequence of other disorders causing pain but that are not associated with those mentioned before as channelopathies.
  • Patients with central nervous system diseased that may complicate the somatosensory testing.
  • The skin biopsy procedure, will not be conducted on those patients with contraindications to do so i.e. anticoagulation therapy, skin infections, etc; that might result in adverse outcomes (if the subject decides to decline the skin biopsy, the inclusion on the study will not be affected).
  • The functional magnetic resonance imaging (fMRI) component will not be performed in subjects that had medical interventions with any device likely to be damaged or moved from its place, at any moment during the fMRI scanning procedure (including cerebral coils or clips, heart pacemakers or defibrillators, heart valve prosthesis, medicine infusion pumps, inner ear implants, neural stimulators, brain shunts, joint replacements/ large metal implants, stents in the heart or arteries, some implants, or some intra-uterine contraceptive devices.
  • Those patients that in the concept of the research team unsuitable for participation in the study.
  • For those undergoing microneurography presence of edema (swelling) or any skin condition at the ankle level that may interfere with the microneurography procedure.
  • Patients with a history of skin allergy or sensitivity will not undergo testing of axon reflex or conditioning challenges.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02696746


Locations
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United Kingdom
Nuffield Department of Clinical Neurosciences Recruiting
Oxford, Oxfordshire, United Kingdom, OX3 9DU
Contact: Juan D Ramirez, MD    +44 1865234541    juan.ramirez@ndcn.ox.ac.uk   
Contact: Andreas Themistocleous, PhD    +44 1865234543    andreas.themistocleous@ndcn.ox.ac.uk   
Principal Investigator: David L H Bennett, MD PhD         
Sponsors and Collaborators
King's College London
University of Oxford
Neuroscience Technologies S.L.P

Publications of Results:
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Responsible Party: King's College London
ClinicalTrials.gov Identifier: NCT02696746     History of Changes
Other Study ID Numbers: 12/LO/0017
First Posted: March 2, 2016    Key Record Dates
Last Update Posted: February 22, 2019
Last Verified: February 2019

Additional relevant MeSH terms:
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Chronic Pain
Erythromelalgia
Channelopathies
Hereditary Sensory and Autonomic Neuropathies
Pain Insensitivity, Congenital
Pain
Neurologic Manifestations
Signs and Symptoms
Peripheral Vascular Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Nervous System Malformations
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Polyneuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Congenital Abnormalities
Genetic Diseases, Inborn