Duloxetine in Osteoarthritis (OA) Pain

This study is currently recruiting participants.
Verified February 2014 by Northwestern University
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Apkar Apkarian, Northwestern University
ClinicalTrials.gov Identifier:
NCT01558700
First received: March 16, 2012
Last updated: February 17, 2014
Last verified: February 2014

March 16, 2012
February 17, 2014
March 2012
April 2014   (final data collection date for primary outcome measure)
brain gray matter volume [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01558700 on ClinicalTrials.gov Archive Site
pain magnitude [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
WOMAC pain
Same as current
Not Provided
Not Provided
 
Duloxetine in Osteoarthritis (OA) Pain
Brain Morphometries in OA Patients Treated With Duloxetine

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Osteoarthritis
  • Drug: Duloxetine
    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.
    Other Name: Cymbalta
  • Drug: Sugar pill
    Matching capsule given once a day for a total of 17 weeks.
    Other Name: Placebo
  • Experimental: Duloxetine
    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.
    Intervention: Drug: Duloxetine
  • Placebo Comparator: Sugar pill
    Matching capsule given once a day for a total of 17 weeks.
    Intervention: Drug: Sugar pill
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
120
December 2014
April 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age: 45-80 years
  • ACR criteria for OA including Kellgren-Lawrence radiographic OA grades II-IV
  • VAS pain score >5/10 within 48 hrs of the phone screen and visit 1 (Screening)
  • Knee OA for a minimum of 12 months
  • Need for daily pain medication to manage symptoms of OA

Exclusion Criteria:

Currently taking MAO inhibitors or any centrally acting drug for analgesia, depression

  • Narrow angle glaucoma
  • Uncontrolled hypertension
  • Co-existing inflammatory arthritis, fibromyalgia or other chronic pain state.
  • If a female, pregnant, trying to become pregnant, or lactating
  • Major depressive disorder
  • Substantial alcohol use or history of significant liver disease
  • Use of MAO inhibitors, triptans, serotonin precursors (tryptophan)
  • Use of potent CYP1A2 inhibitors, Thioridazine, and anti-depressants
  • Diabetes, type 1 or type 2
  • Condition in which the Investigator believes would interfere with the subject's ability to comply with study instructions, or might confound the interpretation of the study results or put the subject at undue risk
  • MRI safety necessitates the exclusion of subjects having one or more of the following:

    • Metal fragments in the eye or face, or having worked previously in the metal industry
    • Implantation of any electronic devices such as (but not limited to) cardiac pacemakers, cardiac, defibrillators, and cochlear implants or nerve stimulators.
    • Surgery on the blood vessels of the brain
    • Claustrophobia (fear of enclosed places)
    • Piercings or tattoos
    • More than 250 lbs in weight
    • Obvious brain abnormalities
Both
40 Years to 80 Years
Yes
Contact: Pain Studies 312-503-2886 PainStudies@northwestern.edu
United States
 
NCT01558700
STU00039556
No
Apkar Apkarian, Northwestern University
Northwestern University
Eli Lilly and Company
Study Director: Thomas Schnitzer, MD, PhD Northwestern University Feinberg School of Medicine
Northwestern University
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP