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

Mass General Brigham

Status: Terminated

Conditions: Chronic Pain

Treatments: Drug: Placebo; Drug: Guanfacine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02192398

1R01DA036564-01 (U.S. NIH Grant/Contract)

2014P-001377

Details and patient eligibility

About

Combination of guanfacine with opioid medication as a standard treatment for chronic pain.

Full description

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

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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120 participants in 3 patient groups, including a placebo group

Guanfacine (2mg)

Active Comparator group

Description:

Subjects will be randomized into 1 of the following 3 treatment groups: 1. guanfacine (2mg) 2. guanfacine (1mg) 3. placebo Subjects will be instructed to take one capsule in the evening for 4 weeks.

Treatment:

Drug: Guanfacine

Guanfacine (1mg)

Active Comparator group

Description:

Subjects will be randomized into 1 of the following 3 treatment groups: 1. guanfacine (2mg) 2. guanfacine (1mg) 3. placebo Subjects will be instructed to take one capsule in the evening for 4 weeks.

Treatment:

Drug: Guanfacine

Placebo

Placebo Comparator group

Description:

Subjects will be randomized into 1 of the following 3 treatment groups: 1. guanfacine (2mg) 2. guanfacine (1mg) 3. placebo Subjects will be instructed to take one capsule in the evening for 4 weeks.

Treatment:

Drug: Placebo