Ignite Creation Date:
2024-05-05 @ 9:52 PM
Last Modification Date:
2024-10-26 @ 10:10 AM
Study NCT ID:
NCT00981149
Status:
COMPLETED
Last Update Posted:
2021-05-25
First Post:
2009-09-18
Brief Title:
Duloxetine for Treatment of Painful Temporomandibular Joint Disorder
Sponsor:
University of Maryland Baltimore
Organization:
University of Maryland Baltimore
Study Overview
Official Title:
Duloxetine for Treatment of Painful Temporomandibular Joint Disorder
Status:
COMPLETED
Status Verified Date:
2021-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Temporomandibular joint disorders TMJD are a family of musculoskeletal disorders that represent the most common chronic orofacial pain condition TMJD is associated with persistent pain in the region of the temporomandibular joint and muscles of the head and neck The purpose of this study is to test duloxetine Cymbalta as a potential treatment for chronic facial pain Duloxetine is FDA approved as an antidepressant and for the chronic pain conditions of fibromyalgia and diabetic neuropathy Chronic facial pain may be linked to Temporomandibular Joint Disorder TMJD which currently has no standard treatment
Detailed Description:
The proposed clinical trial will evaluate the analgesic and adverse effects of duloxetine a serotonin and norepinephrine reuptake inhibitor in comparison to placebo in patients with temporomandibular joint disorder TMJD Duloxetine is approved as an antidepressant and has been shown effective in the chronic pain conditions of fibromyalgia and diabetic neuropathy Decrease in pain and dysfunction and improvement in quality of life and global satisfaction will be assessed over 6 weeks Successful demonstration of a therapeutic effect may provide a basis for clinical use of duloxetine in patients with painful TMJD
Background
TMJD is a heterogeneous family of musculoskeletal disorders associated with the temporomandibular joint the periauricular region and the muscles of the head and neck TMJD has been identified as a major cause of nondental chronic pain in the craniofacial region second only to headache NIH Technology Assessment Conference 1997 Although few population-based epidemiological studies have been conducted studies report the prevalence of TMJD as up to 20 in the adult population Dworkin et al 1990 Schiffman et al 1990 Dworkin and colleagues conducted a series of studies of TMJD using valid and reliable examination and survey procedures Von Korff et al 1988 Dworkin et al 1990 Carlsson and LeResche 1995 and identified 121 of the test population with painful TMJD with a female to male ratio of approximately 71 They also found the annual incidence of developing TMJD to be just over 2 with females tending to show a higher incidence rate than males Von Korff et al 1993 Hence TMJD is common in the general population but it has also been reported that about 20 of patients with early signs and symptoms of TMJD will progress to a persistent pain state Schiffman et al 1990
Several studies of TMJD suggest that patients exhibit a state of CNS hypersensitivity similar to that reported in fibromyalgia Maixner et al 1995 Maixner et al 1998 Sarlani and Greenspan 2003 Sarlani et al 2004 that contributes to the predicted widespread characteristics of the pain Genetic factors that impact increased pain sensitivity psychological traits and sex differences and often coupled with environmental stress may result in a phenotype that is vulnerable to musculoskeletal disease and susceptible to selective pharmacological treatment
In addition to female gender two other factors predict an elevated incidence of these disorders a history of musculoskeletal pain at other body sites and quality of life symptoms typically associated with depression Von Korff et al 1988 Raphael and Marbach 2001 John et al 2003 Patients diagnosed with fibromyalgia often exhibit concurrent orofacial symptomatology that mimics TMJD Ta et al 2002 Sarlani and Greenspan 2003 Sarlani et al 2004 These observations and findings suggest that drugs useful for depression affecting musculoskeletal systems and effective in improving central monoaminergic neurotransmission are prime candidates for the treatment of TMJD For these reasons we hypothesize that selective noradrenergic or combined noradrenergic and serotonin reuptake inhibitors should be effective for TMJD
Lack of research has resulted in a paucity of evidence-based treatment approaches for TMJD Antczak- Bouckoms 1995 List 2003 While NSAIDs are sometimes used there is little evidence for their effectiveness for TMJD Dionne 1997 Gordon et al 1990 1991 except in frank joint involvement Ta et al 2004 and gastrointestinal and renal toxicity limit their long-term use Gabriel et al 1991 Allison et al 1992 Schafer et al 1995 Champion et al 1997 for treatment of chronic pain Use of opioids has been discouraged for this chronic pain condition due to the limitations of long-term use for this drug class DeNucci et al 1996 Dionne 1997 The most promising pharmacologic therapy for TMJD to date has been antidepressants but it is important to note that indication for their clinical use has primarily been extrapolated from other chronic pain conditions McQuay et al 1992 Onghena et al 1992 Only two randomized controlled trials have examined one of the tricyclic antidepressants amitryptyline for TMJD specifically Sharav et all 1987 Rizzatti-Barbosa 2003 Amitryptyline for TMJD demonstrated an average response rate of 40 in these two studies but its adverse effects result in a large percentage of patients discontinuing the drug before achieving pain relief DeNucci et al 1996 resulting in an unfavorable risk to benefit ratio Zitman et al 1990 Taken together there has been insufficient evidence to adopt a pharmacologic standard of care for treatment of TMJD
Duloxetine has shown efficacy for several chronic pain conditions Sultan 2008 including fibromyalgia and appears to be more effective in women than men Arnold 2004 2005 It is well tolerated and effective at a dose of 60 mg daily Sultan 2008 Studies in patients with fibromyalgia Arnold 2004 2005 diabetic neuropathy Goldstein 2005 low back pain Skijaravala 2008 and osteoarthritis Chappell 2008 have shown an analgesic effect at this dose with fewer adverse effects and a lower drop out rate than higher doses In the proposed study subjects randomized to the intervention will use 60 mg of duloxetine given as 30 mg twice daily after a one-week period of 30 mg daily
Given the prevalence of TMJD and the controversial nature of non-pharmacologic therapies such as occlusal alteration intraoral devices and surgery the need exists for pharmacologic treatment that is efficacious but avoids adverse effects that discourage long-term use This study will also provide a basis for future investigations of the etiology and management of painful TMJD
PurposeObjective of this study TMJD represents a prototypic musculoskeletal disease whose characteristics of associated depression comorbidity of fibromyalgia female prevalence increased CNS sensitivity to pain and likely genetic differences among susceptible individuals makes it a disorder that will likely be responsive to duloxetine treatmentThe overall objective is to investigate duloxetine as a potential treatment for chronic pain of TMJD We hypothesize that subjects receiving duloxetine will experience greater analgesia than those receiving placebo
Specifically we will
1 Evaluate the analgesic effect of 30 mg duloxetine twice daily in comparison to matching placebo at baseline BL and follow up over a six week period using the primary outcome measure of change in spontaneous pain 2 Evaluate jaw functioning and evoked pain as measured by range of motion pain with jaw movement and pain pressure thresholds 3 Assess frequency of adverse effects and their impact on patient global satisfaction and study adherence 4 Examine sleep in relationship to pain 5 Evaluate genetic susceptibilty to pain and response to duloxetine
These aims and outcome measures are listed in prioritized order The study is powered on the primary outcome measure of spontaneous pain other measures are exploratory The study is not powered to detect subgroup differences for variables such as gender depression type of TMJD diagnosis or concurrent medications as described later in the Analysis Plan
Research Design The study is a double blind placebo-controlled parallel groups prospective study of duloxetine versus placebo Subjects will be randomized to the investigational treatment group duloxetine or the placebo group At the time of enrollment they will be randomly assigned to study drug or placebo by block randomization for order in a 11 ratio Subjects will be provided acetominophen as a rescue analgesic to use if they feel their pain is not adequately controlled The examiners and subjects will be blind to the group assignment
Background
TMJD is a heterogeneous family of musculoskeletal disorders associated with the temporomandibular joint the periauricular region and the muscles of the head and neck TMJD has been identified as a major cause of nondental chronic pain in the craniofacial region second only to headache NIH Technology Assessment Conference 1997 Although few population-based epidemiological studies have been conducted studies report the prevalence of TMJD as up to 20 in the adult population Dworkin et al 1990 Schiffman et al 1990 Dworkin and colleagues conducted a series of studies of TMJD using valid and reliable examination and survey procedures Von Korff et al 1988 Dworkin et al 1990 Carlsson and LeResche 1995 and identified 121 of the test population with painful TMJD with a female to male ratio of approximately 71 They also found the annual incidence of developing TMJD to be just over 2 with females tending to show a higher incidence rate than males Von Korff et al 1993 Hence TMJD is common in the general population but it has also been reported that about 20 of patients with early signs and symptoms of TMJD will progress to a persistent pain state Schiffman et al 1990
Several studies of TMJD suggest that patients exhibit a state of CNS hypersensitivity similar to that reported in fibromyalgia Maixner et al 1995 Maixner et al 1998 Sarlani and Greenspan 2003 Sarlani et al 2004 that contributes to the predicted widespread characteristics of the pain Genetic factors that impact increased pain sensitivity psychological traits and sex differences and often coupled with environmental stress may result in a phenotype that is vulnerable to musculoskeletal disease and susceptible to selective pharmacological treatment
In addition to female gender two other factors predict an elevated incidence of these disorders a history of musculoskeletal pain at other body sites and quality of life symptoms typically associated with depression Von Korff et al 1988 Raphael and Marbach 2001 John et al 2003 Patients diagnosed with fibromyalgia often exhibit concurrent orofacial symptomatology that mimics TMJD Ta et al 2002 Sarlani and Greenspan 2003 Sarlani et al 2004 These observations and findings suggest that drugs useful for depression affecting musculoskeletal systems and effective in improving central monoaminergic neurotransmission are prime candidates for the treatment of TMJD For these reasons we hypothesize that selective noradrenergic or combined noradrenergic and serotonin reuptake inhibitors should be effective for TMJD
Lack of research has resulted in a paucity of evidence-based treatment approaches for TMJD Antczak- Bouckoms 1995 List 2003 While NSAIDs are sometimes used there is little evidence for their effectiveness for TMJD Dionne 1997 Gordon et al 1990 1991 except in frank joint involvement Ta et al 2004 and gastrointestinal and renal toxicity limit their long-term use Gabriel et al 1991 Allison et al 1992 Schafer et al 1995 Champion et al 1997 for treatment of chronic pain Use of opioids has been discouraged for this chronic pain condition due to the limitations of long-term use for this drug class DeNucci et al 1996 Dionne 1997 The most promising pharmacologic therapy for TMJD to date has been antidepressants but it is important to note that indication for their clinical use has primarily been extrapolated from other chronic pain conditions McQuay et al 1992 Onghena et al 1992 Only two randomized controlled trials have examined one of the tricyclic antidepressants amitryptyline for TMJD specifically Sharav et all 1987 Rizzatti-Barbosa 2003 Amitryptyline for TMJD demonstrated an average response rate of 40 in these two studies but its adverse effects result in a large percentage of patients discontinuing the drug before achieving pain relief DeNucci et al 1996 resulting in an unfavorable risk to benefit ratio Zitman et al 1990 Taken together there has been insufficient evidence to adopt a pharmacologic standard of care for treatment of TMJD
Duloxetine has shown efficacy for several chronic pain conditions Sultan 2008 including fibromyalgia and appears to be more effective in women than men Arnold 2004 2005 It is well tolerated and effective at a dose of 60 mg daily Sultan 2008 Studies in patients with fibromyalgia Arnold 2004 2005 diabetic neuropathy Goldstein 2005 low back pain Skijaravala 2008 and osteoarthritis Chappell 2008 have shown an analgesic effect at this dose with fewer adverse effects and a lower drop out rate than higher doses In the proposed study subjects randomized to the intervention will use 60 mg of duloxetine given as 30 mg twice daily after a one-week period of 30 mg daily
Given the prevalence of TMJD and the controversial nature of non-pharmacologic therapies such as occlusal alteration intraoral devices and surgery the need exists for pharmacologic treatment that is efficacious but avoids adverse effects that discourage long-term use This study will also provide a basis for future investigations of the etiology and management of painful TMJD
PurposeObjective of this study TMJD represents a prototypic musculoskeletal disease whose characteristics of associated depression comorbidity of fibromyalgia female prevalence increased CNS sensitivity to pain and likely genetic differences among susceptible individuals makes it a disorder that will likely be responsive to duloxetine treatmentThe overall objective is to investigate duloxetine as a potential treatment for chronic pain of TMJD We hypothesize that subjects receiving duloxetine will experience greater analgesia than those receiving placebo
Specifically we will
1 Evaluate the analgesic effect of 30 mg duloxetine twice daily in comparison to matching placebo at baseline BL and follow up over a six week period using the primary outcome measure of change in spontaneous pain 2 Evaluate jaw functioning and evoked pain as measured by range of motion pain with jaw movement and pain pressure thresholds 3 Assess frequency of adverse effects and their impact on patient global satisfaction and study adherence 4 Examine sleep in relationship to pain 5 Evaluate genetic susceptibilty to pain and response to duloxetine
These aims and outcome measures are listed in prioritized order The study is powered on the primary outcome measure of spontaneous pain other measures are exploratory The study is not powered to detect subgroup differences for variables such as gender depression type of TMJD diagnosis or concurrent medications as described later in the Analysis Plan
Research Design The study is a double blind placebo-controlled parallel groups prospective study of duloxetine versus placebo Subjects will be randomized to the investigational treatment group duloxetine or the placebo group At the time of enrollment they will be randomly assigned to study drug or placebo by block randomization for order in a 11 ratio Subjects will be provided acetominophen as a rescue analgesic to use if they feel their pain is not adequately controlled The examiners and subjects will be blind to the group assignment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None