Effect of Guanfacine on the Reversal of Opioid-induced Hyperalgesia (OIH)

Study Overview
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Brief Summary
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Combination of guanfacine with opioid medication as a standard treatment for chronic pain.

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

Official Title
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Effect of Guanfacine on the Reversal of Opioid-induced Hyperalgesia (OIH)

Conditions
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Chronic Pain

Intervention / Treatment
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* Drug: Guanfacine
* 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 6 months VAS score of 4-8, despite opioid therapy On a stable morphine equivalent dose of at least 60mg/day and ≤ 240mg/day for at least 3 months Exclusion Criteria Has taken Methadone, Suboxone, Fentanyl, and/or Tramadol in the last six (6) months Has taken guanfacine (or other alpha-2AR agonists) in the last six (6) months Changes to current or adding new pain treatment while enrolled in the study (i.e. opiates, epidural steroid injection) will be reviewed by the study physician Unable to independently provide informed written consent Sensory deficits at site of QST, such as peripheral neuropathy Intolerable allergies or has had a severe adverse reaction to study medication (i.e. guanfacine, lactose, vitamin B2 a.k.a. riboflavin) Takes vitamin B2 > 1.6mg/day during the study Pregnant or breastfeeding Pending litigation related to neck or back pain 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 severe cardiovascular disease (i.e. arrhythmia - prolonged QT interval > 440ms), cerebrovascular disease/accident (i.e., stroke), 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) will be reviewed by a study physician Bradycardia (resting heart rate < 60 bpm) will be reviewed by a study physician Subjects are on antihypertensive drugs (e.g., a beta-blocker) that result in hypotension and/or bradycardia as defined above Tests positive for 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 currently prescribed 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 as well as possible confounding side effects. 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 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Guanfacine (2mg)<br>Subjects will be randomized into 1 of the following 3 treatment groups: guanfacine (2mg) guanfacine (1mg) placebo Subjects will be instructed to take one capsule in the evening for 4 weeks. | Drug: Guanfacine<br>* Subjects will be randomized into 1 of the following 3 treatment groups: guanfacine (2mg) guanfacine (1mg) placebo To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 4 weeks of drug treatment (guanfacine or placebo).<br>* Other names: Tenex, Intuniv;|
| Active Comparator: Guanfacine (1mg)<br>Subjects will be randomized into 1 of the following 3 treatment groups: guanfacine (2mg) guanfacine (1mg) placebo Subjects will be instructed to take one capsule in the evening for 4 weeks. | Drug: Guanfacine<br>* Subjects will be randomized into 1 of the following 3 treatment groups: guanfacine (2mg) guanfacine (1mg) placebo To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 4 weeks of drug treatment (guanfacine or placebo).<br>* Other names: Tenex, Intuniv;|
| Placebo Comparator: Placebo<br>Subjects will be randomized into 1 of the following 3 treatment groups: guanfacine (2mg) guanfacine (1mg) placebo Subjects will be instructed to take one capsule in the evening for 4 weeks. | Drug: Placebo<br>* Subjects will be randomized into 1 of the following 3 treatment groups: guanfacine (2mg) guanfacine (1mg) placebo To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 4 weeks of drug treatment (guanfacine or placebo).<br>* Other names: Placebo, 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 3 treatment groups. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heat Pain Threshold | Subjects will be measured for their heat pain threshold using QST. The testing will be done at 3 of the 4 visits. | 4 weeks | 
| Heat Pain Tolerance | Subjects will be measured for their heat pain tolerance using QST. The testing will be done at 3 of the 4 visits. | 4 weeks | 
| Temporal Pain Summation | Subjects will be measured for their temporal pain summation using QST. The testing will be done at 3 of the 4 visits. | 4 weeks | 
| Detecting Diffuse Noxious Inhibitory Control (DNIC) | Subjects will be measured for their Diffuse Noxious Inhibitory Control (DNIC). The testing will be done at 3 of the 4 visits. | 4 weeks | 
| Heat Sensation | Subjects will be measured for their heat sensation using QST. The testing will be done at 3 of the 4 visits. | 4 weeks | 

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