Exploring the Genetics of Neuropathic Pain (GeNeup)

In the present study the investigators will search for new genetic variants relevant for the development of neuropathic pain.

Study Overview

• Status: Recruiting
• Conditions: Neuropathic Pain; Polyneuropathies; Genetic Predisposition
• Intervention / Treatment: Genetic: Nerve conduction Studies

Detailed Description

Neuropathic pain is defined as "pain caused by a lesion or disease of the somatosensory nervous system". Neuropathic pain is a huge health problem worldwide, with an estimated prevalence of 7-8 % in the general population. In the present study the investigators will search for new genetic variants relevant for the development of this type of pain.

Peripheral nerve lesions only progress to neuropathic pain in some patients, yet is not completely understood why or how. Genetic studies of patients with rare neuropathic disorders have been important for elucidating novel molecular mechanisms of neuropathic pain, and new drugs for neuropathic pain are now being developed based on these findings. By using genetic association studies, one may identify new genetic variants which may help to identify key molecular mechanisms for a larger group of patients with neuropathic pain.

This project will use existing population-based cohorts, as well as establish a specific registry and biobank for patients with neuropathy in order to address these specific needs. This will allow the investigators to identify a large number of individuals with probable neuropathic pain and individuals with pain-free peripheral neuropathy (disease controls). International collaboration will contribute to study a large group of patients, which will be important in order to reach the project's goals. The results from the project are expected to increase current knowledge on the mechanisms of neuropathic pain, opening up new opportunities for innovative and improved treatments.

Dissemination of results will be organized in close collaboration with patient representatives, and will be done regularly throughout the course of the project. The will focus both on internal dissemination to the participating hospitals, and external dissemination through participation in conferences, submissions to scientific journals and by publishing patient-friendly information booklets and proactively informing media outlets and patient organizations.

• Study Type: Observational
• Enrollment (Estimated): 5000

Contacts and Locations

• Study Contact: Name: Kristian B. Nilsen, M.D; Phone Number: +4791372241; Email: uxnikq@ous-hf.no

Study Locations

• Norway
  • Bergen, Norway, 5021
    • Recruiting
    • Haukeland University Hospital
    • Contact: Ina Hjelland, M.D.; Phone Number: +4755975000; Email: ina.hjelland@helse-bergen.no
  • Oslo, Norway, 0450
    • Recruiting
    • Oslo University Hospital
    • Contact: Kristian B. Nilsen, M.D.; Phone Number: +4791372241; Email: uxnikq@ous-hf.no
    • Contact: Øystein Dunker, M.D.; Phone Number: +4793293484; Email: anoyes@ous-hf.no
    • Sub-Investigator: Øystein Dunker
  • Stavanger, Norway, 4011
    • Recruiting
    • Helse Stavanger HF
    • Contact: Marie Bu Kvaløy, M.D.; Phone Number: +4751518430; Email: marie.bu.kvaloy@sus.no
  • Tromsø, Norway, 9019
    • Recruiting
    • University Hospital of North Norway
    • Contact: Sissel Løseth, M.D.; Phone Number: +4777627102; Email: sissel.loseth@unn.no
  • Trondheim, Norway, 7030
    • Recruiting
    • St. Olavs Hospital
    • Contact: Trond Sand, M.D.; Phone Number: +4772576006; Email: trond.sand@ntnu.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

All patients that are referred for suspected distal symmetric polyneuropathy and meet the inclusion criteria, will be included in the project. Furthermore, there will be collected blood tests from patients with definite and probable polyneuropathy.

Description

Inclusion Criteria:

1. The patient is between 18 and 70 years old.
2. The patient has consented.
3. The patient is referred for evaluation of possible distal symmetric polyneuropathy (DSPN).
4. The patient has filled out the questionnaires.

Exclusion Criteria:

1. The patient is too sick to participate (eg. bedridden, fever).
2. The patient is unable to consent (eg. dementia, speech problems, psychiatric disorder).
3. Inflammatory acute polyneuropathy.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Polyneuropathy with pain; Clinical and diagnostic test evaluation for the establishment of polyneuropathy with pain.	Genetic: Nerve conduction Studies; Patients will be genotyped for comparison of patients With and without pain, With different clinical subgroups as mentioned.; Other Names: Genetical analysis
Polyneuropathy without pain; Clinical and diagnostic test evaluation for the establishment of polyneuropathy without pain.	Genetic: Nerve conduction Studies; Patients will be genotyped for comparison of patients With and without pain, With different clinical subgroups as mentioned.; Other Names: Genetical analysis
Diabetic polyneuropathy with pain; Clinical and diagnostic test evaluation for the establishment of diabetic polyneuropathy with pain.	Genetic: Nerve conduction Studies; Patients will be genotyped for comparison of patients With and without pain, With different clinical subgroups as mentioned.; Other Names: Genetical analysis
Diabetic polyneuropathy without pain; Clinical and diagnostic test evaluation for the establishment of diabetic polyneuropathy without pain.	Genetic: Nerve conduction Studies; Patients will be genotyped for comparison of patients With and without pain, With different clinical subgroups as mentioned.; Other Names: Genetical analysis
Carpal tunnel syndrome with pain; Clinical and diagnostic test evaluation for the establishment of carpal tunnel syndrome with pain.	Genetic: Nerve conduction Studies; Patients will be genotyped for comparison of patients With and without pain, With different clinical subgroups as mentioned.; Other Names: Genetical analysis
Carpal tunnel syndrome without pain; Clinical and diagnostic test evaluation for the establishment of carpal tunnel syndrome without pain.	Genetic: Nerve conduction Studies; Patients will be genotyped for comparison of patients With and without pain, With different clinical subgroups as mentioned.; Other Names: Genetical analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic variants associated with neuropathic pain.	Relevant genotypes will be found using genome-wide association study (GWAS) methodology, ie. with no assumptions regarding which genetic variants that may be relevant (no hypotheses regarding specific variants). This is going to be conducted by using array genotyping (SNPs) in order to identify genetic variants that might be associated with neuropathic pain. Genetic variants will be defined and named according to standard practice, without any room for local or study specific adaptations.	Baseline
Phenotype; neuropathic pain yes/no	Patients will be divided in two groups; neuropathy With pain (= neuropathic pain) and neuropathy without pain. For definition of neuropathic pain, the Neupsig guidelines (Finnerup et al, Pain 2016) will be used.It is estimated that about 600 patients will be included yearly for this purpose	Baseline
Phenotype; subgroup analysis of patients with neuropathic pain based on grading of pain	Patients with neuropathic pain will be further subdivided in groups based on pain reports. Pain will be graded using validated questionnaires. The "Brief Pain Inventory-BPI" (Cleeland et al, 1994) questionnaire will be used as primary resource for pain grading, on a scale from 0 to 10 (0: no pain, 1-3: mild pain, 4-10: strong pain).	Baseline

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: Danish Pain Research Center; University Hospital of North Norway; University of Oxford; Helse Stavanger HF; Haukeland University Hospital; St. Olavs Hospital; Oslo Metropolitan University
• Investigators: Study Chair: John Anker Zwart, M.D., Oslo University Hospital; Principal Investigator: David Benett, M.D., University of Oxford; Principal Investigator: Ina Hjelland, M.D., Haukeland University Hospital; Principal Investigator: Margreth Grotle, Pr., Oslo Metropolitan University; Principal Investigator: Marie Bu Kvaløy, M.D., Helse Stavanger HF; Principal Investigator: Trond Sand, M.D., St. Olavs Hospital; Principal Investigator: Sissel Løseth, M.D., University of North Norway; Principal Investigator: Troels Jensen, M.D., Danish pain research senter

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 11, 2018
• First Submitted That Met QC Criteria: March 1, 2019
• First Posted (Actual): March 5, 2019

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: validity; reliability
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Pain; Neurologic Manifestations; Disease Attributes; Neuromuscular Diseases; Peripheral Nervous System Diseases; Disease Susceptibility; Neuralgia; Polyneuropathies; Genetic Predisposition to Disease
• Other Study ID Numbers: 2017/1593

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No