Clinical trial NCT01681264: Effect of Guanfacine on Opioid-induced Hyperalgesia (OIH) and Tolerance
Official title: Effect of Guanfacine on Opioid-induced Hyperalgesia (OIH) and Tolerance
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Pain
Keywords: Pain
Pain Management
Back pain
Neck pain
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute on Drug Abuse (NIDA)
First posted: 2012-09-07
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Dual medication (guanfacine and morphine) as a standard treatment for chronic pain.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Quantitative Sensory Testing (QST)
timeFrame: 12 weeks
Secondary outcomes:
measure: Heat Pain Threshold
timeFrame: 12 weeks
measure: Heat Pain Tolerance
timeFrame: 12 weeks
measure: Temporal Pain Summation
timeFrame: 12 weeks
measure: Detecting Diffuse Noxious Inhibitory Control (DNIC)
timeFrame: 12 weeks
measure: Heat Sensation
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Center for Translational Pain Research
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Jianren Mao, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: