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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by University Hospital Inselspital, Berne
Sponsor:
Collaborators:
University of Bern
University of Zurich
Aalborg University
Information provided by:
University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier:
NCT01179828
First received: August 10, 2010
Last updated: December 27, 2012
Last verified: December 2012
  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 3

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:


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: December 2014
Estimated Primary Completion Date: December 2013 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
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
  More Information

Publications:
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: December 27, 2012
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
Oxycodone
Imipramine
Clobazam
Tolterodine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
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

ClinicalTrials.gov processed this record on October 02, 2014