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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

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.

Condition or disease Intervention/treatment Phase
Low Back Pain Drug: Oxycodone 15mg Drug: Clobazam Drug: Imipramine Drug: Tolterodine Phase 3

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Official Title: Linking Altered Central Pain Processing and Genetic Polymorphism to Drug Efficacy in Chronic Low Back Pain
Study Start Date : July 2010
Actual Primary Completion Date : April 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Back Pain

Arm Intervention/treatment
Active Comparator: 1
Oxycodone 15mg
Drug: Oxycodone 15mg
15mg single administration p.o.

Active Comparator: 2
Clobazam 20mg
Drug: Clobazam
20mg single administration p.o.

Active Comparator: 3
Imipramine 75mg
Drug: Imipramine
75mg single administration p.o.

Placebo Comparator: 4
Tolterodine 1mg
Drug: Tolterodine
1 mg single administration p.o.

Primary Outcome Measures :
  1. Difference in NRS(pain scale) between measurement after and before drug administration [ Time Frame: 07/2012 ]

Secondary Outcome Measures :
  1. Patients global impression of change scale after drug administration [ Time Frame: 07/2012 ]
  2. Pharmacogenetic variables(see before) [ Time Frame: 07/2012 ]
  3. Pharmacokinetics: measure of Imipramine and desipramine blood levels [ Time Frame: 07/2012 ]
  4. Reliability of repeated quantitative sensory testing in the same patient [ Time Frame: 12/2010 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01179828

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Andreas Siegenthaler
Dep. of Anesthesiolgy and Pain therapy, Bern University Hospital, Switzerland, 3010 Bern
Sponsors and Collaborators
University Hospital Inselspital, Berne
University of Bern
University of Zurich
Aalborg University
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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
Publications of Results:
Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Dr Med Andreas Siegenthaler, Inselspital Bern Identifier: NCT01179828    
Other Study ID Numbers: KEK 213/09
grant: SPUM no. 33CM30_124117
First Posted: August 11, 2010    Key Record Dates
Last Update Posted: April 6, 2016
Last Verified: April 2016
Keywords provided by University Hospital Inselspital, Berne:
Quantitative sensory testing
Drug efficacy
Low back pain syndrome
Additional relevant MeSH terms:
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Back Pain
Low Back Pain
Neurologic Manifestations
Tolterodine Tartrate
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Urological Agents
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Adrenergic Agents
Anti-Anxiety Agents