Duloxetine in Osteoarthritis (OA) Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01558700
Recruitment Status : Completed
First Posted : March 20, 2012
Results First Posted : December 29, 2014
Last Update Posted : December 29, 2014
Eli Lilly and Company
Information provided by (Responsible Party):
Apkar Apkarian, Northwestern University

Brief 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.

Condition or disease Intervention/treatment Phase
Osteoarthritis Drug: Duloxetine Drug: Sugar pill Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Brain Morphometries in OA Patients Treated With Duloxetine
Study Start Date : March 2012
Actual Primary Completion Date : April 2014
Actual Study Completion Date : August 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arm Intervention/treatment
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.
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

Placebo Comparator: Sugar pill
Matching capsule given once a day for a total of 17 weeks.
Drug: Sugar pill
Matching capsule given once a day for a total of 17 weeks.
Other Name: Placebo

Primary Outcome Measures :
  1. Change in Brain Gray Matter Volume [ Time Frame: 16 weeks compared to baseline ]
    The change in gray matter volume is evaluated by subtracting the volume after the treatment (week 16) to the volume before treatment (baseline)

Secondary Outcome Measures :
  1. Change in Pain Magnitude [ Time Frame: 16 weeks compared to baseline ]
    The Western Ontario and McMaster Osteoarthritis Index (WOMAC) score change was assess by subtracting WOMAC score after treatment (week 16) to the baseline WOMAC score. WOMAC score has a range from 0 up to 96, higher score meaning worse condition. The outcome is the decrease in WOMAC scores, meaning that the higher is the decrease, the most improvement in the condition.

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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01558700

United States, Illinois
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Eli Lilly and Company
Study Director: Thomas Schnitzer, MD, PhD Northwestern University Feinberg School of Medicine

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Apkar Apkarian, Professor, Northwestern University Identifier: NCT01558700     History of Changes
Other Study ID Numbers: STU00039556
First Posted: March 20, 2012    Key Record Dates
Results First Posted: December 29, 2014
Last Update Posted: December 29, 2014
Last Verified: December 2014

Keywords provided by Apkar Apkarian, Northwestern University:
gray matter

Additional relevant MeSH terms:
Duloxetine Hydrochloride
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Serotonin and Noradrenaline Reuptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Antidepressive Agents
Psychotropic Drugs
Dopamine Agents