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

Chronic Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02192398
• Other study ID #: 2014P-001377
• Secondary ID: 1R01DA036564-01
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 2014
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: December 2024
• 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 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.

Related Conditions & MeSH terms

• Chronic Pain
• Hyperalgesia

Intervention

Drug:
• Guanfacine
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).
• Placebo
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).

Locations

Country	Name	City	State
United States	MGH 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 3 treatment groups.	4 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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