Duloxetine in Osteoarthritis (OA) Pain
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.
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 Design
Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science
Conditions
Osteoarthritis
Intervention
duloxetine, sugar pill
Location
Northwestern University Feinberg School of Medicine
Chicago
Illinois
United States
60611
Status
Recruiting
Source
Northwestern University
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01558700
- Information obtained from ClinicalTrials.gov on May 06, 2013
Medical and Biotech [MESH] Definitions
Sugar Alcohol Dehydrogenases
Reversibly catalyzes the oxidation of a hydroxyl group of sugar alcohols to form a keto sugar, aldehyde or lactone. Any acceptor except molecular oxygen is permitted. Includes EC 1.1.1.; EC 1.1.2. and EC 1.1.99.
Capsule Endoscopes
A pill sized videocamera encased in a capsule. It is designed to be swallowed and subsequently traverse the gastrointestinal tract while transmitting diagnostic images along the way.
Phosphoenolpyruvate Sugar Phosphotransferase System
The bacterial sugar phosphotransferase system (PTS) that catalyzes the transfer of the phosphoryl group from phosphoenolpyruvate to its sugar substrates (the PTS sugars) concomitant with the translocation of these sugars across the bacterial membrane. The phosphorylation of a given sugar requires four proteins, two general proteins, Enzyme I and HPr and a pair of sugar-specific proteins designated as the Enzyme II complex. The PTS has also been implicated in the induction of synthesis of some catabolic enzyme systems required for the utilization of sugars that are not substrates of the PTS as well as the regulation of the activity of adenylate cyclase. EC 2.7.1.-.
Glycosides
Any compound that contains a constituent sugar, in which the hydroxyl group attached to the first carbon is substituted by an alcoholic, phenolic, or other group. They are named specifically for the sugar contained, such as glucoside (glucose), pentoside (pentose), fructoside (fructose), etc. Upon hydrolysis, a sugar and nonsugar component (aglycone) are formed. (From Dorland, 28th ed; From Miall's Dictionary of Chemistry, 5th ed)
Aspartic Acid
One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.
Clinical Trials
A Single-Blind Placebo Run-in Study of Duloxetine for Activity-Limiting Osteoarthritis Pain
This will be a single-blind, placebo-run-in trial. Subjects will be informed that they may receive duloxetine or placebo during the course of the trial. All subjects will, in fact, receive...
A Study of Duloxetine in Patients With Osteoarthritis Knee Pain
The primary purpose of this study is to determine if duloxetine 60 mg QD once daily reduces pain severity in patients with osteoarthritis(OA) knee pain compared with placebo.
Duloxetine Versus Placebo for Osteoarthritis Knee Pain
The primary purpose of this study is to determine if duloxetine reduces pain severity in patients with osteoarthritis knee pain.
Efficacy of Etoricoxib 60 mg in Modifying Pain Hypersensitivity in People With Knee Osteoarthritis
This study aims to better understand the way in which painful osteoarthritis affects different people and whether an anti-inflammatory medication such as Arcoxia (etoricoxib) can help to m...
The primary objective of this study is to provide duloxetine to investigators for the treatment of patients who have previously participated in neuroscience duloxetine clinical trials and...
PubMed Articles
Abstract Objective: To compare opioid utilization and healthcare costs over a 1-year period following the initiation with duloxetine versus other standard of care (SOC) treatments among patients with...
The synthesis of (R)-Duloxetine is described. Dynamic kinetic resolution of β-hydroxynitrile rac-1 using Candida antarctica lipase B (CALB, N435) and ruthenium catalyst 6 afforded β-cyano acetate (R...
Abstract Objective: To determine the efficacy, tolerability, and safety of duloxetine when added to oral nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with osteoarthritis (OA) of the...
Cost-Utility Analysis of Duloxetine in Osteoarthritis: A US Private Payer Perspective.
BACKGROUND: Duloxetine has recently been approved in the USA for chronic musculoskeletal pain, including osteoarthritis and chronic low back pain. The cost effectiveness of duloxetine in osteoarthriti...
Core temperature measurement with an ingestible telemetry pill has been scarcely investigated during extreme rates of temperature change, induced by short high-intensity exercise in the heat. Therefor...
