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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01179828
Recruitment Status : Completed
First Posted : August 11, 2010
Last Update Posted : April 6, 2016
University of Bern
University of Zurich
Aalborg University
Information provided by:
University Hospital Inselspital, Berne

Tracking Information
First Submitted Date  ICMJE August 10, 2010
First Posted Date  ICMJE August 11, 2010
Last Update Posted Date April 6, 2016
Study Start Date  ICMJE July 2010
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 10, 2010)
Difference in NRS(pain scale) between measurement after and before drug administration [ Time Frame: 07/2012 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01179828 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2010)
  • Patients global impression of change scale after drug administration [ Time Frame: 07/2012 ]
  • Pharmacogenetic variables(see before) [ Time Frame: 07/2012 ]
  • Pharmacokinetics: measure of Imipramine and desipramine blood levels [ Time Frame: 07/2012 ]
  • Reliability of repeated quantitative sensory testing in the same patient [ Time Frame: 12/2010 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Linking Altered Central Pain Processing and Genetic Polymorphism to Drug Efficacy in Chronic Low Back Pain (Predictio)
Official Title  ICMJE Linking Altered Central Pain Processing and Genetic Polymorphism to Drug Efficacy in Chronic Low Back Pain
Brief Summary

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.

Detailed Description


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.


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.


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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE Low Back Pain
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 10, 2010)
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2015
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01179828
Other Study ID Numbers  ICMJE KEK 213/09
grant: SPUM no. 33CM30_124117
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr Med Andreas Siegenthaler, Inselspital Bern
Study Sponsor  ICMJE University Hospital Inselspital, Berne
Collaborators  ICMJE
  • University of Bern
  • University of Zurich
  • Aalborg University
Investigators  ICMJE
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
PRS Account University Hospital Inselspital, Berne
Verification Date April 2016

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