Painful Channelopathies Study

NCT02696746 | Unknown

• 1 other identifier: 12/LO/0017
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Erythromelalgia; Pain Insensitivity, Congenital; Hereditary Sensory and Autonomic Neuropathies; Chronic Pain

Outcome Measures

Primary Outcomes (1)

• Pain score

  Seven days pain diary of 4 or above. Patients will have 7-days pain diaries with a numeric rating scale from 0 to 10.

  Day 7

Secondary Outcomes (17)

• Age

  Day 1

• Gender

  Day 1

• Ethnicity

  Day 1

• Detailed medical history

  Day 1

• Pain related anxiety

  Day 1

Study Arms (1)

Pain related conditions

Subjects with painful or painless conditions (observational study, no interventions)

Other: Observation

Interventions

Observation OTHER

No intervention

Pain related conditions

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients and family members affected by chanelopathic pain related conditions.

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• King's College London: lead
• University of Oxford: collaborator
• Neuroscience Technologies S.L.P: collaborator

Study Sites (1)

Nuffield Department of Clinical Neurosciences

Oxford, Oxfordshire, OX3 9DU, United Kingdom

RECRUITING

Related Publications (1)

• Ramirez JD, Habib AM, Cox JJ, Themistocleous AC, McMahon SB, Wood JN, Bennett DL. Null mutation in SCN9A in which noxious stimuli can be detected in the absence of pain. Neurology. 2014 Oct 21;83(17):1577-80. doi: 10.1212/WNL.0000000000000913. Epub 2014 Sep 24. No abstract available.

  PMID: 25253744 RESULT

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

MeSH Terms

Conditions

Erythromelalgia; Pain Insensitivity, Congenital; Hereditary Sensory and Autonomic Neuropathies; Chronic Pain

Interventions

Observation

Condition Hierarchy (Ancestors)

Peripheral Vascular Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nervous System Malformations; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Congenital Abnormalities; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2016
• First Posted: March 2, 2016
• Study Start: February 1, 2012
• Primary Completion: June 1, 2021
• Last Updated: September 17, 2019

Record last verified: 2019-02

Locations

GB (1)