Linking Altered Central Pain Processing and Genetic Polymorphism to Drug Efficacy in Chronic Low Back Pain (Predictio)
Condition: Low Back Pain
MeSH terms: Back Pain; Low Back Pain
Study type: Interventional
Phase: Phase 3

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
    

Intervention name(s): Oxycodone 15mg; Clobazam; Imipramine; Tolterodine
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 15mg single administration p.o.; 20mg single administration p.o.; 75mg single administration p.o.; 1 mg single administration p.o.
Intervention MeSH terms: Oxycodone; Clobazam; Imipramine; Tolterodine Tartrate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: Quantitative sensory testing; Drug efficacy; Low back pain syndrome; Imipramine; Oxycodone; Clobazam; Tolterodine