A Retrospective Study to Identify New "Omics" Biomarkers of Chronic/Persistent Low Back Pain

Low back pain (LBP) is one of the most common medical problems encountered in daily life; it is related to disability and work absence and accounts for high economical costs in Western societies.

Low-back pain is a diverse group of mixed pain syndromes (neuropathic and nociceptive) with different molecular pathologies at different structural levels displaying similar clinical manifestations. Currently, there are limited biomarkers (mostly imaging) or clinical findings that can be used objectively to help the physician in precise anatomic diagnosis leading to the safest and most cost-effective treatment for the patient (reduction of direct and indirect costs and improvement of treatment efficacy).

The main aim of this trial is to identify all "omics biomarkers" associated with susceptibility to chronic/persistent LBP and its different pathophysiology.

Study Overview

• Status: Completed
• Conditions: Persistent/Chronic Low Back Pain

Detailed Description

Retrospective observational multinational clinical study, with a case control design.

Investigators will compare "omic biomarkers" between patients with and without persistent chronic low back pain (CLBP).

"OMIC" biomarkers investigated will be genetics, glycomics and activomic. Genetics through GWA studies has already obtained important results in pain research; however concerning low back pain, there is not yet suitable genotype-phenotype correlations helpful to stratify patients.

Glycomics is an emerging field that has recently been identified as a priority for the next decade by the US National Academies of Science. Many common complex diseases will be associated with specific changes in glycan structures. In addition, common genetic polymorphisms influencing glycosylation and consequent differences in glycome composition could be important diagnostic and prognostic markers. The first studies reporting protein glycosylation in large human population samples have been recently published by partners in the consortium. Reliable identification of valid associations between specific glyco-phenotypes and predisposition for the development or progression of a specific disease requires analysis of thousands of patients.

Activomics: combines data about enzymatic activity of numerous numerous post-translational modification proteins in an integrated model which provides dynamic characterization of the current state of an organism. In this project information about numerous proteases, kinases, phosphatases and glycosidases will be collected and used to complement the existing phenotype information.

• Study Type: Observational

Contacts and Locations

Study Locations

• Australia
  • Perth, Australia
    • Edith Cowan University (ECU)
• Belgium
  • Genk, Belgium
    • Multidisciplinary Pain Centre, Hospital Oost-Limburg (ZOL)
• Croatia
  • Zabok, Croatia
    • "St.Catharine" Orthopedics, Surgery, Neurology and Physical Medicine and Rehabilitation Specialty Hospital (St-Cat)
• Italy
  • Parma, Italy
    • Anesthesia and Pain Therapy Department, Università degli Studi di Parma (UNIPR)
  • Pavia, Italy
    • Fondazione IRCCS Policlinico San Matteo (OSM)
• United States
  • North Carolina
    • Winston-salem, North Carolina, United States
      • The Center for Clinical Research (CPI)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Cases will be collected at each participating centre. Every effort will be made to accumulate a well phenotyped cohort of patients with persistent CLBP, sub-grouped into 6 categories: discogenic pain, spinal stenosis (congenital or acquired), facet joint pain, sacroiliac joint pain, low back pain with radicular pain (not predominant radicular pain) and widespread low back pain.

Controls (patients without chronic/persistent pain as defined above) will be retrieved from 2 different sources:

Existing biobanks of healthy subjects which have collected information about chronic/persistent back pain.

Subjects from the companion prospective study on acute LBP who will not have developed CLBP.

Age (decades) and gender distribution of controls will be similar to cases.

Description

Inclusion Criteria of patients with persistent CLBP:

• age: older than 18;
• chronic/persistent pain (pain lasting longer than 12 weeks) between the costal margins and gluteal fold, with or without symptoms into one or both legs
• written informed consent signed;
• Caucasian ancestry

Inclusion Criteria of healthy volunteers:

• age: older than 18;
• without any chronic/persistent pain (pain lasting longer than 12 weeks) in the last one year;
• written informed consent signed;
• Caucasian ancestry

Exclusion Criteria:

• evidence of clinically unstable disease;
• severe psychiatric disorder (excluding mild depression) or mental impairment;
• recent history ( < 1 year) of spinal fracture;
• pain in the back due to spinal tumor or infection;
• pregnancy

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GENETIC OUTCOME	The primary objective is to recognize genetic variants associated with persistent CLBP patients compared to patients without chronic/persistent pain. Through a Genetic Wide Association Study (GWAS) investigators will correlate genetic variants associated with persistent CLBP in a wide, international population of European ancestry.	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GLYCOMIC AND ACTIVOMIC OUTCOME	Recognize Glycomic and Activomic data associated with persistent CLBP patients compared to patients without chronic/persistent pain. The sample size will better defined after the first interim analysis of first 400 patients.	30 months
STRATIFICATION OF OUR POPULATION	All "omic" data will be compared stratifying our population according to: Pathophysiology: discogenic pain, spinal stenosis, facet joint pain, sacroiliac joint pain, low back pain with radicular pain (not predominant radicular pain) and widespread pain.; pain intensity; response to treatment; duration of pain	30 months

Collaborators and Investigators

• Sponsor: University of Parma
• Collaborators: King's College London; Helmholtz Zentrum München; GENOS; Ip Research Consulting Sasu; YURII AULCHENKO
• Investigators: Principal Investigator: MASSIMO ALLEGRI, MD, Fondazione IRCCS Policlinico San Matteo di Pavia

Publications and helpful links

General Publications

• Allegri M, De Gregori M, Minella CE, Klersy C, Wang W, Sim M, Gieger C, Manz J, Pemberton IK, MacDougall J, Williams FM, Van Zundert J, Buyse K, Lauc G, Gudelj I, Primorac D, Skelin A, Aulchenko YS, Karssen LC, Kapural L, Rauck R, Fanelli G; PainOMICS Group. 'Omics' biomarkers associated with chronic low back pain: protocol of a retrospective longitudinal study. BMJ Open. 2016 Oct 19;6(10):e012070. doi: 10.1136/bmjopen-2016-012070.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (ACTUAL): February 1, 2016
• Study Completion (ACTUAL): February 1, 2016

Study Registration Dates

• First Submitted: January 14, 2014
• First Submitted That Met QC Criteria: January 15, 2014
• First Posted (ESTIMATE): January 16, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): September 26, 2016
• Last Update Submitted That Met QC Criteria: September 23, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: pain; low back pain; GWAS; glycomics; activomics
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain
• Other Study ID Numbers: Pain-OMICS RT