Effect of Combined Morphine and Duloxetine on Chronic Pain

Study Overview
=================
Brief Summary
-----------------
A double-blind, randomized, and placebo-controlled clinical study examining whether duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), could enhance opioid analgesia and reduce overall opioid use. Positive outcomes will help improve the overall effectiveness of clinical opioid therapy and reduce unnecessary opioid dose escalation.

Official Title
-----------------
Effect of Combined Morphine and Duloxetine on Chronic Pain

Conditions
-----------------
Chronic Low Back Pain, Chronic Neck Pain

Intervention / Treatment
-----------------
* Drug: Morphine
* Drug: Duloxetine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is 18-70 years old. Subject has chronic neck or back pain for at least 3 months. Subject has a VAS ≥ 5. Has not taken duloxetine in the last 3 months. Has not taken an opioid in the last 3 months, but has taken one in the past without sufficient pain control OR has never taken opioids but has failed at 3 (or more) non-opioid treatments. Exclusion Criteria: Subject has major psychiatric disorders requiring recent hospitalization (within 3 months) such as major depression, bipolar disorder, schizophrenia, anxiety disorder, or psychotic disorder. Subject is using illicit drugs detected by urine toxicology/drug screen. Subject is pregnant or lactating/breast feeding. Subject is allergic to morphine or duloxetine. Subject is on an antidepressant including serotonin-norepinephrine reuptake inhibitors (SNRI), selective serotonin reuptake inhibitor (SSRI), tricyclic antidepressant. Subject has a history of suicidal attempts or current suicidal ideation. Subject takes monoamine oxidase inhibitors, antipsychotics, triptan drugs such as sumatriptan, lithium, linezolid, tramadol (Ultram), St. John's Wort, central nervous system (CNS) stimulants such as amphetamine, methylphenidate, methamphetamine, phentermine, diethylpropion, sibutramine, cocaine, or thioridazine. Subject has uncontrolled narrow-angle glaucoma. Subject has sensory deficits on arms or Raynaud's Syndrome. Subject has a pending litigation related to chronic pain condition. Subject is on methadone or suboxone treatment for addiction.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Morphine, Duloxetine<br>Subjects will take a maximum dose of 60 mg/day of extended release morphine capsules and 60 mg of duloxetine capsules. | Drug: Morphine<br>* Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.<br>* Other names: Morphine Sulfate Contin, Morphine Sulfate Instant Release;Drug: Duloxetine<br>* Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.<br>* Other names: Cymbalta;|
| Placebo Comparator: Morphine, Placebo Duloxetine<br>Subjects will take a maximum dose of 60 mg/day of extended release morphine capsules and placebo duloxetine capsules. | Drug: Morphine<br>* Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.<br>* Other names: Morphine Sulfate Contin, Morphine Sulfate Instant Release;Drug: Placebo<br>* Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.<br>* Other names: Sugar pill;|
| Placebo Comparator: Placebo Morphine, Duloxetine<br>Subjects will take placebo morphine capsules and 60 mg of duloxetine capsules. | Drug: Duloxetine<br>* Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.<br>* Other names: Cymbalta;Drug: Placebo<br>* Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.<br>* Other names: Sugar pill;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Opioid Dose | The investigators will compare overall opioid dose between the morphine/duloxetine group and the morphine/placebo group and compare rescue dose among all three groups. | 10 weeks | 
| Visual Analog Scale (VAS) | To examine changes in VAS scores and to determine total versus rescue opioid use after each treatment | 10 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pain Management, Pain