Clinical trial NCT02037763: A Prospective Trial to Identify Biomarkers Involved in the Transition From Acute to Persistent Chronic Low Back Pain
Official title: A Prospective Controlled Trial to Identify Biomarkers Involved in the Transition From Acute to Persistent Chronic Low Back Pain
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Low Back Pain
Chronic Low Back Pain
Keywords: Low back pain
GWAS
Glycomics
Activomics
Epigenetics
Lead sponsor: University of Parma
Sponsor class: OTHER
Collaborators: name: GENOS
name: Ip Research Consulting Sasu
name: Helmholtz Zentrum München
name: YURII AULCHENKO
name: King's College London
First posted: 2014-01-16
Enrollment: 5000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Each clinical centre will identify patients with an episode of acute LBP, with or without irradiation, referred from primary care physicians, orthopaedic specialists or directly selected in the emergency room (accessing hospital for acute low back pain).

The enrolment will be competitive among the participating clinical centres.

Brief summary: This is a prospective observational cohort multinational clinical study. There are no biomarkers to help predict in which patients acute low back pain (LBP) will transform into chronic low back pain (CLBP). Human variability and different common comorbidities complicate the picture and make stratification of patients into correct subgroups difficult. However, drugs act by targeting specific molecular pathways and are therefore efficient only in a subgroup of patients sharing common molecular pathology and common genetics. Both CLBP and disc degeneration are known to be heritable. Little investigation has taken place for genetic variants in CLBP. The main aim of this trial is to identify "omics biomarkers" associated with the transition from acute (single episode of low back pain) to persistent/chronic LBP (pain lasting more than 12 weeks).

Detailed description: Investigators will link and relate clinical data to a multiple "omics" analysis in patients developing persistent chronic symptoms (defined as pain that persists 3 months or more), after an episode of acute LBP. The development of persistent chronic pain will be assessed at 3 months after the acute episode.

"OMIC" biomarkers investigated will be genetics, epigenetics, glycomics and activomic.

Genetics through genome wide association studies (GWAS) 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.

Epigenetic regulation is a universal tool that higher organisms use to adapt to changes in the environment. While environmental factors, such as diet influence enzymatic processes only while they are directly present, their prolonged effects can be achieved through the cell memory of epigenetic marks. Various elements of the membrane signal transduction system were reported to be regulated by epigenetic mechanisms.

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.

"Omics" data will be compared stratifying population according to pain characteristics, pain intensity, response to treatment and duration of pain. In a subgroup of patients, "omics" data will be compared stratifying population according to pain pathophysiology: discogenic pain, spinal stenosis, facet joint pain, sacroiliac joint pain, low back pain with radicular pain (radicular pain not predominant) and widespread low back pain.

Eligibility criteria: Inclusion Criteria:

* age: older than 18;
* acute episode of pain between the costal margins and gluteal fold, with or without symptoms into one or both legs lasting less than 6 weeks;
* written informed consent signed;
* Caucasian ancestry

Exclusion Criteria:

* evidence of clinically unstable disease;
* severe psychiatric disorder (excluding mild depression) or mental impairment;
* history (in the last 6 months) of persistent chronic low back pain or acute LBP episodes
* recent history (\< 1 year) of spinal fracture;
* pain in the back due to spinal tumor or infection;
* pregnancy;

Primary outcomes:
measure: Genetic outcome
timeFrame: 54 months
Secondary outcomes:
measure: Glycomic and Activomic outcome
timeFrame: 54 months
measure: Epigenetic outcome
timeFrame: 54 months
measure: Next-generation sequencing outcome
timeFrame: 54 months
measure: Stratification based on pain characteristics
timeFrame: 54 months
measure: Stratification based on pain pathophysiology
timeFrame: 54 months
measure: Stratification based on 6 months follow-up
timeFrame: 54 months
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: The Center for Clinical Research (CPI)
state: North Carolina
city: Perth
country: Australia
facility: Edith Cowan University (ECU)
city: Genk
country: Belgium
facility: Multidisciplinary Pain Centre, Hospital Oost-Limburg (ZOL)
city: Zabok
country: Croatia
facility: "St.Catharine" Orthopedics, Surgery, Neurology and Physical Medicine and Rehabilitation Specialty Hospital (St-Cat)
city: Parma
country: Italy
facility: Anesthesia and Pain Therapy Department, Università degli Studi di Parma (UNIPR)
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo (OSM)
city: London
country: United Kingdom
facility: King's College London (KCL)
Study officials:
affiliation: Pain Therapy Service Azienda Ospedaliera Universitaria Parma Italy
name: MASSIMO ALLEGRI, MD
role: PRINCIPAL_INVESTIGATOR
References: