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

Sponsor:	University Hospital Inselspital, Berne
Collaborators:	CTU Bern, Clinical Trials Unit, Bern University of Zurich Aalborg University
Information provided by:	University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier:	NCT01179828

Purpose

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	Intervention	Phase
Low Back Pain	Drug: Oxycodone 15mg Drug: Clobazam Drug: Imipramine Drug: Tolterodine	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Basic Science
Official Title:	Linking Altered Central Pain Processing and Genetic Polymorphism to Drug Efficacy in Chronic Low Back Pain

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Back Pain

Drug Information available for: Imipramine Clobazam Oxycodone Imipramine hydrochloride Tolterodine Tolterodine tartrate Oxycodone hydrochloride

U.S. FDA Resources

Further study details as provided by University Hospital Inselspital, Berne:

Primary Outcome Measures:

Difference in NRS(pain scale) between measurement after and before drug administration [ Time Frame: 07/2012 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	150
Study Start Date:	July 2010
Estimated Study Completion Date:	July 2012
Estimated Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

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

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01179828

Contacts

Contact: Andreas Siegenthaler, Dr Med	+41316322111	andreas.siegenthaler@insel.ch
Contact: Pascal H Vuilleumier, Dr Med	+41316322111	pascal.vuilleumier@insel.ch

Locations

Switzerland
Andreas Siegenthaler	Recruiting
Dep. of Anesthesiolgy and Pain therapy, Bern University Hospital, Switzerland, 3010 Bern
Contact: Andreas Siegenthaler, Dr Med +41316322111 andreas.siegenthaler@insel.ch
Contact: Pascal H Vuilleumier, Dr Med +41316322111 pascal.vuilleumier@insel.ch
Principal Investigator: Pascal H Vuilleumier, Dr Med
Sub-Investigator: Sabine Mlekusch, Dr Med

Sponsors and Collaborators

University Hospital Inselspital, Berne

CTU Bern, Clinical Trials Unit, Bern

University of Zurich

Aalborg University

Investigators

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

More Information

Publications:

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. Epub 2009 Apr 19. Review.

Foulkes T, Wood JN. Pain genes. PLoS Genet. 2008 Jul 25;4(7):e1000086. Review.

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.

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.

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

Responsible Party:	Dr Med Andreas Siegenthaler, Inselspital Bern
ClinicalTrials.gov Identifier:	NCT01179828 History of Changes
Other Study ID Numbers:	KEK 213/09, grant: SPUM no. 33CM30_124117
Study First Received:	August 10, 2010
Last Updated:	October 3, 2011
Health Authority:	Switzerland: Independent Local Research Ethic Commission (Ethikkommission); Switzerland: Swiss Agency for therapeutic products (Swissmedic)

Keywords provided by University Hospital Inselspital, Berne:

Quantitative sensory testing
Drug efficacy
Low back pain syndrome
Imipramine

Oxycodone
Clobazam
Tolterodine

Additional relevant MeSH terms:

Back Pain
Low Back Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Imipramine
Oxycodone
Clobazam
Tolterodine
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses

Pharmacologic Actions
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs
Narcotics
Central Nervous System Depressants
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Analgesics, Opioid
Anticonvulsants
Muscarinic Antagonists

ClinicalTrials.gov processed this record on February 09, 2012