Clinical trial NCT01179828: Linking Altered Central Pain Processing and Genetic Polymorphism to Drug Efficacy in Chronic Low Back Pain (Predictio)
Official title: Linking Altered Central Pain Processing and Genetic Polymorphism to Drug Efficacy in Chronic Low Back Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Low Back Pain
Keywords: Quantitative sensory testing
Drug efficacy
Low back pain syndrome
Imipramine
Oxycodone
Clobazam
Tolterodine
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: University of Bern
name: University of Zurich
name: Aalborg University
First posted: 2010-08-11
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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: 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

Eligibility criteria: 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)

Primary outcomes:
measure: Difference in NRS(pain scale) between measurement after and before drug administration
timeFrame: 07/2012
Secondary outcomes:
measure: Patients global impression of change scale after drug administration
timeFrame: 07/2012
measure: Pharmacogenetic variables(see before)
timeFrame: 07/2012
measure: Pharmacokinetics: measure of Imipramine and desipramine blood levels
timeFrame: 07/2012
measure: Reliability of repeated quantitative sensory testing in the same patient
timeFrame: 12/2010
Other outcomes:
Locations:
city: Dep. of Anesthesiolgy and Pain therapy
country: Switzerland
facility: Andreas Siegenthaler
state: Bern University Hospital
Study officials:
affiliation: University Hospital Bern, Switzerland
name: Michele Curatolo, Prof
role: STUDY_CHAIR
affiliation: University Hospital Bern, Switzerland
name: Andreas Siegenthaler, Dr Med
role: STUDY_DIRECTOR
affiliation: University Hospital Bern, Switzerland
name: Pascal H Vuilleumier, Dr Med
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Curatolo M, Arendt-Nielsen L, Petersen-Felix S. Central hypersensitivity in chronic pain: mechanisms and clinical implications. Phys Med Rehabil Clin N Am. 2006 May;17(2):287-302. doi: 10.1016/j.pmr.2005.12.010.
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citation: Schliessbach J, Siegenthaler A, Butikofer L, Vuilleumier P, Juni P, Arendt-Nielsen L, Curatolo M. Quantitative sensory tests fairly reflect immediate effects of oxycodone in chronic low-back pain. Scand J Pain. 2017 Oct;17:107-115. doi: 10.1016/j.sjpain.2017.07.004. Epub 2017 Aug 9.
citation: Siegenthaler A, Schliessbach J, Vuilleumier PH, Juni P, Zeilhofer HU, Arendt-Nielsen L, Curatolo M. Linking altered central pain processing and genetic polymorphism to drug efficacy in chronic low back pain. BMC Pharmacol Toxicol. 2015 Sep 16;16:23. doi: 10.1186/s40360-015-0023-z.