Duloxetine in Osteoarthritis (OA) Pain

December 16, 2014 updated by: Apkar Apkarian, Northwestern University

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University Feinberg School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
16 weeks compared to baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
16 weeks compared to baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Collaborators

Eli Lilly and Company

Investigators

  • Study Director: Thomas Schnitzer, MD, PhD, Northwestern University Feinberg School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2012

Primary Completion (ACTUAL)

April 1, 2014

Study Completion (ACTUAL)

August 1, 2014

Study Registration Dates

First Submitted

March 16, 2012

First Submitted That Met QC Criteria

March 19, 2012

First Posted (ESTIMATE)

March 20, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

December 29, 2014

Last Update Submitted That Met QC Criteria

December 16, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU00039556

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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