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

Sponsor

University Hospital Inselspital, Berne (Other)

Overall Status

Completed

CT.gov ID

NCT01179828

Collaborator

University of Bern (Other), University of Zurich (Other), Aalborg University (Other)

150

Enrollment

Location

Arms

Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

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

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

Study Design

Study Type:

Interventional

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 :

Jul 1, 2010

Actual Primary Completion Date :

Apr 1, 2015

Actual Study Completion Date :

Dec 1, 2015

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

Difference in NRS(pain scale) between measurement after and before drug administration [07/2012]

Secondary Outcome Measures

Patients global impression of change scale after drug administration [07/2012]
Pharmacogenetic variables(see before) [07/2012]
Pharmacokinetics: measure of Imipramine and desipramine blood levels [07/2012]
Reliability of repeated quantitative sensory testing in the same patient [12/2010]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	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

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