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A Prospective Trial to Identify Biomarkers Involved in the Transition From Acute to Persistent Chronic Low Back Pain

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified September 2014 by IRCCS Policlinico S. Matteo
Sponsor:
Collaborators:
GENOS DOO
IP RESEARCH CONSULTING SASU
Helmholtz Center Munich - German Research Center for Environmental Health (HMGU)
YURII AULCHENKO
King's College London
Information provided by (Responsible Party):
Massimo Allegri, IRCCS Policlinico S. Matteo
ClinicalTrials.gov Identifier:
NCT02037763
First received: January 14, 2014
Last updated: September 3, 2014
Last verified: September 2014
  Purpose

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).


Condition
Acute Low Back Pain
Chronic Low Back Pain

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Prospective Controlled Trial to Identify Biomarkers Involved in the Transition From Acute to Persistent Chronic Low Back Pain

Resource links provided by NLM:


Further study details as provided by IRCCS Policlinico S. Matteo:

Primary Outcome Measures:
  • Genetic outcome [ Time Frame: 54 months ] [ Designated as safety issue: No ]

    To investigate the associations between genetic factors and the development of persistent chronic LBP, 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.

    Existing and newly generated GWAs will be analyzed and their possible correlation with the risk of pain becoming persistent chronic will be detected in a wide, international population of caucasian ancestry.



Secondary Outcome Measures:
  • Glycomic and Activomic outcome [ Time Frame: 54 months ] [ Designated as safety issue: No ]
    Recognize Glycomic and Activomic data associated with patients who develop CLBP compared to patients who do not develop CLBP after an episode of acute LBP. The sample size will better defined after the first interim analysis of first 400 patients.

  • Epigenetic outcome [ Time Frame: 54 months ] [ Designated as safety issue: No ]

    Investigators will identify CpG methylation patterns that may be associated with the development and maintenance of persistent chronic LBP pain after an episode of acute LBP in the first 200 patients who develop CLBP and first 200 patients who will not develop it.

    In the same cohort of 400 patients, investigators will analyze microRNAs (miRNAs) to investigate their role in predicting risk of persistent chronic pain after acute episode, opioid tolerance and response to therapy after the beginning of opioid therapy.


  • Next-generation sequencing outcome [ Time Frame: 54 months ] [ Designated as safety issue: No ]
    Investigators will detect rare variants with strong or modest effects on LBP symptoms and response to therapy using next generation sequencing of candidate genes in 200 incident cases with persistent chronic pain and 200 controls. In particular, investigators will analyze new genetic variants that may impact on intervertebral disc stability, new variants modifying inflammation, variants of pain signalling, new variants in genes encoding analgesic drug metabolism and other genes from literature search.

  • Stratification based on pain characteristics [ Time Frame: 54 months ] [ Designated as safety issue: No ]
    "Omics" data will be compared stratifying our population according to pain characteristics, pain intensity, response to treatment and duration of pain.

  • Stratification based on pain pathophysiology [ Time Frame: 54 months ] [ Designated as safety issue: No ]
    In a subgroup of patients, "omics" data will be compared stratifying our 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.

  • Stratification based on 6 months follow-up [ Time Frame: 54 months ] [ Designated as safety issue: No ]
    "Omics" data will be also compared stratifying our population according to the persistence of pain at 6 months despite receiving a treatment following current guidelines.


Biospecimen Retention:   Samples With DNA

Whole blood samples will be collected at recruitment in all enrolled patients. Blood samples will be collected also at the 3 months and 6 months follow up visits in patients who will develop CLBP after the episode of acute LBP.


Estimated Enrollment: 5000
Study Start Date: December 2014
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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;
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02037763

Contacts
Contact: MASSIMO ALLEGRI, MD m.allegri@smatteo.pv.it

Locations
United States, North Carolina
The Center for Clinical Research (CPI) Not yet recruiting
Winston-Salem, North Carolina, United States
Principal Investigator: LEONARDO KAPURAL, MD         
Australia
Edith Cowan University (ECU) Not yet recruiting
Perth, Australia
Principal Investigator: WEI WANG, PROF         
Belgium
Multidisciplinary Pain Centre, Hospital Oost-Limburg (ZOL) Not yet recruiting
Genk, Belgium
Principal Investigator: JAN VAN ZUNDERT, MD         
Croatia
"St.Catharine" Orthopedics, Surgery, Neurology and Physical Medicine and Rehabilitation Specialty Hospital (St-Cat) Not yet recruiting
Zabok, Croatia
Principal Investigator: DRAGAN PRIMORAC, PROF         
Italy
Anesthesia and Pain Therapy Department, Università degli Studi di Parma (UNIPR) Not yet recruiting
Parma, Italy
Principal Investigator: GUIDO FANELLI, PROF         
Fondazione IRCCS Policlinico San Matteo (OSM) Not yet recruiting
Pavia, Italy, 27100
Contact: MASSIMO ALLEGRI, MD       m.allegri@smatteo.pv.it   
Principal Investigator: MASSIMO ALLEGRI, MD         
Sub-Investigator: CRISTINA E MINELLA, MD         
Sub-Investigator: MANUELA DE GREGORI, PHD         
United Kingdom
King's College London (KCL) Not yet recruiting
London, United Kingdom
Principal Investigator: FRANCES WILLIAMS, MD         
Sponsors and Collaborators
IRCCS Policlinico S. Matteo
GENOS DOO
IP RESEARCH CONSULTING SASU
Helmholtz Center Munich - German Research Center for Environmental Health (HMGU)
YURII AULCHENKO
King's College London
Investigators
Principal Investigator: MASSIMO ALLEGRI, MD Fondazione IRCCS Policlinico San Matteo - Pavia
  More Information

No publications provided

Responsible Party: Massimo Allegri, MD, IRCCS Policlinico S. Matteo
ClinicalTrials.gov Identifier: NCT02037763     History of Changes
Other Study ID Numbers: Pain-OMICS PRT
Study First Received: January 14, 2014
Last Updated: September 3, 2014
Health Authority: Italy: Ethics Committee
Italy: Ministry of Health
Italy: The Italian Medicines Agency

Keywords provided by IRCCS Policlinico S. Matteo:
Low back pain
GWAS
Glycomics
Activomics
Epigenetics

Additional relevant MeSH terms:
Back Pain
Low Back Pain
Nervous System Diseases
Neurologic Manifestations
Pain
Signs and Symptoms

ClinicalTrials.gov processed this record on November 25, 2014