Linking Altered Central Pain Processing and Genetic Polymorphism to Drug Efficacy in Chronic Low Back Pain (Predictio)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by University Hospital Inselspital, Berne
Sponsor:
Collaborators:
University of Bern
University of Zurich
Aalborg University
Information provided by:
University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier:
NCT01179828
First received: August 10, 2010
Last updated: December 27, 2012
Last verified: December 2012

August 10, 2010
December 27, 2012
July 2010
December 2013   (final data collection date for primary outcome measure)
Difference in NRS(pain scale) between measurement after and before drug administration [ Time Frame: 07/2012 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01179828 on ClinicalTrials.gov Archive Site
  • Patients global impression of change scale after drug administration [ Time Frame: 07/2012 ] [ Designated as safety issue: No ]
  • Pharmacogenetic variables(see before) [ Time Frame: 07/2012 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: measure of Imipramine and desipramine blood levels [ Time Frame: 07/2012 ] [ Designated as safety issue: No ]
  • Reliability of repeated quantitative sensory testing in the same patient [ Time Frame: 12/2010 ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Linking Altered Central Pain Processing and Genetic Polymorphism to Drug Efficacy in Chronic Low Back Pain (Predictio)
Linking Altered Central Pain Processing and Genetic Polymorphism to Drug Efficacy in Chronic Low Back Pain

Drug therapy in patients with chronic low back pain is a major challenge for physicians. One of the problems is the lacking knowledge in prediction of drug efficacy in a chosen patient. Usually one of the classes of pain medication is given to patients with a similar clinical picture, although different pain mechanisms may be responsible for this clinical picture.

Another reason for variable drug efficacy are genetic polymorphisms, this may be the reason why an unique drug produces different responses (from a lacking analgesic effect up to excessive effect or side-effects.

Quantitative sensory testing is a method that documents alterations in the pain perception system. Linking genetic polymorphisms to quantitative sensory testing may give us a tool for anticipation of drug efficacy.

Background

Drug therapy is an essential part of pain treatment. However, only a minor part of pain patients benefits from the available treatments or is able to tolerate the drugs. One important limitation of drug therapy is lack of instruments to predict their effect. Indeed, in clinical practice "classes" of drugs (e.g. antidepressants) are given to "classes" of patients (e.g. neuropathic pain patients). However, within those classes of patients very different pain mechanisms are likely to underlie the pain condition in different patients. If drugs affect part of these mechanisms, they will not work in all patients. Another reason for variability in drug responses is genetic variation leading to a spectrum of different responses to analgesics, from lack of efficacy to exaggerated responses, up to intolerable adverse effects.

Quantitative sensory testing comprises methods that document alterations and reorganization of the nociceptive system. Measuring an abnormal result in a chronic pain patient may provide us with the information that the underlying pain pathways somehow must be altered. An essential question is whether this information can be linked to drug efficacy in a mechanism-based treatment approach. A further important question is whether assessing genetic polymorphisms can explain different drug effects and hence help selecting the appropriate therapeutic strategy for individual patients.

Objective

We will test the hypothesis that there is a correlation between disturbances in specific pain mechanisms as assessed by quantitative sensory tests and analgesic efficacy after single-dose drug administration in patients with chronic low back pain. Genetic factors affecting drug metabolism and pain sensitivity will be analyzed as additional explanatory variables for drug efficacy.

Methods

Quantitative sensory testing: Heat pain threshold and tolerance, Ice water testing with central modulation of nociceptive input (DNIC), electrical pain detection and temporal summation (skin probe), pressure algometry with pain detection and threshold Drugs investigated: Imipramine, Oxycodone, Clobazam Blood samples: pharmacogenetics: Cytochrome variants CYP2D6, CYP2C19, CYP3A4, COMT haplotypes, CGH-1 variants, A118G of mu opioid receptor gene variants pharmacokinetics: kinetics of imipramine and desipramine

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Low Back Pain
  • Drug: Oxycodone 15mg
    15mg single administration p.o.
  • Drug: Clobazam
    20mg single administration p.o.
  • Drug: Imipramine
    75mg single administration p.o.
  • Drug: Tolterodine
    1 mg single administration p.o.
  • Active Comparator: 1
    Oxycodone 15mg
    Intervention: Drug: Oxycodone 15mg
  • Active Comparator: 2
    Clobazam 20mg
    Intervention: Drug: Clobazam
  • Active Comparator: 3
    Imipramine 75mg
    Intervention: Drug: Imipramine
  • Placebo Comparator: 4
    Tolterodine 1mg
    Intervention: Drug: Tolterodine

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
150
December 2014
December 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Low back pain with NRS>2
  • Chronic low back pain since more than 6 months

Exclusion Criteria

  • pregnancy
  • use of pain medication other than paracetamol and ibuprofen in the last 7 days
  • suspicion of radicular pain
  • suspicion of intervertebral disk herniation
  • foraminal intervertebral stenosis
  • suspicion of polyneuropathy
  • diabetes
  • parkinson disease
  • alzheimer disease
  • glaucoma
  • prostata hyperplasia or voiding problems
  • known heart rhythm problems
  • heart insufficiency NYHA 3-4
  • Systemic inflammatory disease
  • Ongoing oncologic disease
  • drug or alcohol abuse
  • Significant depressive disease (BDI-FS>9)
Both
18 Years to 80 Years
No
Contact: Andreas Siegenthaler, Dr Med +41316322111 andreas.siegenthaler@insel.ch
Contact: Pascal H Vuilleumier, Dr Med +41316322111 pascal.vuilleumier@insel.ch
Switzerland
 
NCT01179828
KEK 213/09, grant: SPUM no. 33CM30_124117
Yes
Dr Med Andreas Siegenthaler, Inselspital Bern
University Hospital Inselspital, Berne
  • University of Bern
  • University of Zurich
  • Aalborg University
Study Chair: Michele Curatolo, Prof University Hospital Bern, Switzerland
Study Director: Andreas Siegenthaler, Dr Med University Hospital Bern, Switzerland
Principal Investigator: Pascal H Vuilleumier, Dr Med University Hospital Bern, Switzerland
University Hospital Inselspital, Berne
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP