Duloxetine in Osteoarthritis (OA) Pain
Condition: Osteoarthritis
MeSH terms: Osteoarthritis
Study type: Interventional
Phase: Phase 4

Summary: 
      This study aims to determine in people with knee Osteoarthritis (OA) if relief of pain after
      treatment with either duloxetine or placebo is associated with changes in brain anatomy.
    

Detailed description: 
      This study and the hypotheses to be tested arise from work done in our group evaluating brain
      cortical changes in people with chronic back pain. These studies demonstrated a loss of about
      1.5 cc of neocortical gray matter per year of living with the condition, not including gray
      matter lost due to aging. Since this original publication, more than ten studies have
      replicated this basic result, showing that distinct chronic pain conditions are associated
      with specific brain anatomical reorganization, characterized by regional decreases in grey
      matter density. Recently, other studies have shown that when chronic pain is completely
      reversed, these anatomical changes seem to at least partially reverse within the time span of
      4-12 months, providing evidence for a time window for reversal of grey matter abnormalities A
      fundamental question that arises from these recent studies is the extent of reversibility of
      the brain atrophy associated with chronic pain following continuous use of a pain-relieving
      drug. Apkarian's lab has generated strong evidence that the brain anatomy of subjects with
      osteoarthritis (OA) is dramatically different from that of healthy subjects. Given that
      recent data show that hip replacement OA reverses brain atrophy, the investigators can now
      hypothesize with greater confidence that an effective analgesic should also reverse at least
      some of the brain atrophy observed in OA. Thus, a study in patients with chronic knee OA
      treated with duloxetine provides a unique opportunity to answer this question. Since OA
      patients in this study will have a single new agent for four months, one can directly examine
      the effects of treatment in relation to progression or regression of brain atrophy. One can
      also examine whether or not a placebo, which is thought to reflect attentional and
      motivational states, affects changes in atrophy, and if so, to what extent.

      The investigators consider the brain atrophy in chronic pain to be an overall marker of the
      extent of nervous system reorganization a subject has developed while living with the
      condition. Animal models of various chronic pain conditions repeatedly provide evidence for
      this idea, showing, for example, dramatic changes in the way pain is processed in the
      periphery, the spinal cord, and at the level of individual neurons. The investigators presume
      that these changes are the same ones contributing to atrophy in human chronic pain. However,
      most of underlying mechanisms remain to be uncovered. In addition, humans suffering from
      chronic pain exhibit a large number of cognitive and emotional deficits. The investigators
      presume that these deficits are directly related to the brain atrophies discovered in chronic
      pain conditions. Unfortunately, there are no direct studies linking brain regional atrophies
      to cognitive abilities in chronic pain, although such preliminary studies are underway in
      Apkarian's lab. Thus, in addition to the answering the previous questions, the present study
      will also allow us to investigate the extent to which reversing atrophy corresponds to
      reversing plasticity at multiple levels in the nervous system, as well as whether such
      reversal also corresponds to improvements in cognitive and emotional abilities.
    

Intervention name(s): Duloxetine; Sugar pill
Intervention type(s): Drug; Drug
Intervention description(s): Duloxetine capsule 30mg once a day for one week, then 60mg once a day for 15 weeks, then 30mg once a day for one week.; Matching capsule given once a day for a total of 17 weeks.
Other intervention name(s): Cymbalta; Placebo
Intervention MeSH terms: Duloxetine Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: osteoarthritis; pain; brain; gray matter