Effect of Guanfacine on Opioid-induced Hyperalgesia (OIH) and Tolerance

Study Overview
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Brief Summary
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Dual medication (guanfacine and morphine) as a standard treatment for chronic pain.

Detailed Description
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This aim proposes that guanfacine would be a useful drug to deter Opioid-Induced Hyperalgesia (OIH) when combined with an opioid (morphine) in chronic pain management.

Official Title
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Effect of Guanfacine on Opioid-induced Hyperalgesia (OIH) and Tolerance

Conditions
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Chronic Pain

Intervention / Treatment
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* Drug: Morphine
* Drug: Guanfacine 1mg
* Drug: Guanfacine 2mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria 18-65 years old Chronic neck or back pain condition for at least 3 months VAS score of 4-8 Has not taken an opioid for the last 3 months Has not taken guanfacine (or other alpha-2AR agonists) for the last 6 months Exclusion Criteria Sensory deficits at site of QST, such as peripheral neuropathy Allergic to or has had a severe adverse reaction to study medication (i.e. opioids, guanfacine, lactose, vitamin B2 a.k.a. riboflavin) Cannot tolerate study drugs' maximum doses Takes vitamin B2 > 1.6mg/day during the study Pregnant or breastfeeding Pending litigation Diagnosed with Raynaud's syndrome Has other chronic pain conditions such as fibromyalgia or joint osteoarthritis that are predominant over back and neck pain with regard to its intensity (VAS) Has known pre-existing cardiovascular disease (i.e. arrhythmia - prolonged QT interval > 440ms), cerebrovascular disease, hepatic or renal impairment, CNS condition, metabolic condition, or history of syncope Hypotension (SBP < 90 mmHg and DBP < 60 mmHg for female or SBP < 100 mmHg and DBP < 60 mmHg for male; measured while in a sitting position) or bradycardia (resting heart rate < 60 bpm) Subjects are on antihypertensive drugs (e.g., a beta-blocker) that result in hypotension and/or bradycardia as defined above Tests positive for non-study opioids, illicit drugs, marijuana, or non-prescribed drugs Major psychiatric disorders that required hospitalization in the past 6 months such as: major depression, bipolar disorder, schizophrenia, anxiety disorder, or psychotic disorders Currently in a treatment program for alcohol or drug abuse, or currently on methadone or buprenorphine (i.e. suboxone, subutex) for treatment of addiction, or stimulants for treatment of ADHD History of substance or alcohol abuse (meets DSM IV criteria) per medical record or subject admission Subjects are on medications that serve as CYP3A4/5 inhibitors or CYP3A4 inducers including, but are not limited to, valproic acid, macrolide antibiotics, antifungal drugs, St. John wort, ACE inhibitors, nefazodone (antidepressant), calcium channel blockers, H2-receptor antagonists, anti-HIV or AIDS drugs, and antiepileptic drugs Subjects are on medications that are ligands for alpha2-adrenergic receptors including antipsychotic drugs (e.g. clozapine) and tricyclic or tetracyclic antidepressants (e.g. imipramine, mirtazapine, mianserin). Any medications taken by a subject at the enrollment will be reviewed regarding their compatibility with guanfacine and morphine as well as possible confounding side effects. In addition, subjects will be warned of side effects of morphine such as sedation, respiratory depression at the enrollment. Subjects will be allowed to take non-opioid pain medications except for gabapentinoids and amitriptyline/nortriptyline as far as such medications do not have incompatibility with morphine and guanfacine.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Morphine:Placebo<br> | Drug: Morphine<br> <br> * Other names: MS Contin;Drug: Placebo<br> <br> * Other names: Sugar Pill;|
| Active Comparator: Morphine:Guanfacine 1mg<br> | Drug: Morphine<br> <br> * Other names: MS Contin;Drug: Guanfacine 1mg<br> <br> * Other names: Tenex;|
| Active Comparator: Morphine:Guanfacine 2mg<br> | Drug: Morphine<br> <br> * Other names: MS Contin;Drug: Guanfacine 2mg<br> <br> * Other names: Tenex;|
| Active Comparator: Placebo:Guanfacine 2mg<br> | Drug: Guanfacine 2mg<br> <br> * Other names: Tenex;Drug: Placebo<br> <br> * Other names: Sugar Pill;|
| Placebo Comparator: Placebo:Placebo<br> | Drug: Placebo<br> <br> * Other names: Sugar Pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative Sensory Testing (QST) | Quantitative Sensory Testing (QST) results will be used to compare the 5 treatment groups. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heat Pain Threshold | Subjects will be measured for their heat pain threshold using Quantitative Sensory Testing (QST). The testing will be done at 5 of the 6 visits. | 12 weeks | 
| Heat Pain Tolerance | Subjects will be measured for their heat pain tolerance using Quantitative Sensory Testing (QST). The testing will be done at 5 of the 6 visits. | 12 weeks | 
| Temporal Pain Summation | Subjects will be measured for their temporal pain summation using Quantitative Sensory Testing (QST). The testing will be done at 5 of the 6 visits. | 12 weeks | 
| Detecting Diffuse Noxious Inhibitory Control (DNIC) | Subjects will be measured for their Diffuse Noxious Inhibitory Control (DNIC). The testing will be done at 5 of the 6 visits. | 12 weeks | 
| Heat Sensation | Subjects will be measured for their heat sensation using Quantitative Sensory Testing (QST). The testing will be done at 5 of the 6 visits. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Pain Management, Back pain, Neck pain