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

Chronic Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01681264
• Other study ID #: 2013P-001510
• Secondary ID: 1R01DA036564-01
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: November 2013
• Est. completion date: December 2023

Study information

• Verified date: March 2023
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: December 2023
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Pain
• Hyperalgesia

Intervention

Drug:
• Morphine

• Guanfacine 1mg

• Guanfacine 2mg

• Placebo

Locations

Country	Name	City	State
United States	Center for Translational Pain Research	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantitative Sensory Testing (QST)	Quantitative Sensory Testing (QST) results will be used to compare the 5 treatment groups.	12 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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