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

Low Back Pain Clinical Trial

— Predictio  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01179828
• Other study ID #: KEK 213/09
• Secondary ID: grant: SPUM no.
• Status: Completed
• Phase: Phase 3
• First received: August 10, 2010
• Last updated: April 5, 2016
• Start date: July 2010
• Est. completion date: December 2015

Study information

• Verified date: April 2016
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: EthikkommissionSwitzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: December 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Back Pain
• Low Back Pain

Intervention

Drug:
• Oxycodone 15mg
15mg single administration p.o.
• Clobazam
20mg single administration p.o.
• Imipramine
75mg single administration p.o.
• Tolterodine
1 mg single administration p.o.

Locations

Country	Name	City	State
Switzerland	Andreas Siegenthaler	Dep. of Anesthesiolgy and Pain therapy	Bern University Hospital

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne	Aalborg University, University of Bern, University of Zurich

Country where clinical trial is conducted

Switzerland, 

References & Publications (5)

Arendt-Nielsen L, Yarnitsky D. Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera. J Pain. 2009 Jun;10(6):556-72. doi: 10.1016/j.jpain.2009.02.002. Epub 2009 Apr 19. Review. — View 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. Review. — View Citation

Foulkes T, Wood JN. Pain genes. PLoS Genet. 2008 Jul 25;4(7):e1000086. doi: 10.1371/journal.pgen.1000086. Review. — View Citation

Markenson JA, Croft J, Zhang PG, Richards P. Treatment of persistent pain associated with osteoarthritis with controlled-release oxycodone tablets in a randomized controlled clinical trial. Clin J Pain. 2005 Nov-Dec;21(6):524-35. — View Citation

Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005454. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in NRS(pain scale) between measurement after and before drug administration		07/2012	No
Secondary	Patients global impression of change scale after drug administration		07/2012	No
Secondary	Pharmacogenetic variables(see before)		07/2012	No
Secondary	Pharmacokinetics: measure of Imipramine and desipramine blood levels		07/2012	No
Secondary	Reliability of repeated quantitative sensory testing in the same patient		12/2010	No