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

March 13, 2023 updated by: Jianren Mao, MD, PhD, Massachusetts General Hospital
Dual medication (guanfacine and morphine) as a standard treatment for chronic pain.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

200

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Center for Translational Pain Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Morphine:Placebo
Drug: Placebo
Other Names:
  • Sugar Pill
Drug: Morphine
Other Names:
  • MS Contin
Active Comparator: Morphine:Guanfacine 1mg
Drug: Morphine
Other Names:
  • MS Contin
Drug: Guanfacine 1mg
Other Names:
  • Intuniv
  • Tenex
Active Comparator: Morphine:Guanfacine 2mg
Drug: Morphine
Other Names:
  • MS Contin
Drug: Guanfacine 2mg
Other Names:
  • Intuniv
  • Tenex
Active Comparator: Placebo:Guanfacine 2mg
Drug: Placebo
Other Names:
  • Sugar Pill
Drug: Guanfacine 2mg
Other Names:
  • Intuniv
  • Tenex
Placebo Comparator: Placebo:Placebo
Drug: Placebo
Other Names:
  • Sugar Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quantitative Sensory Testing (QST)
Time Frame: 12 weeks
Quantitative Sensory Testing (QST) results will be used to compare the 5 treatment groups.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Heat Pain Threshold
Time Frame: 12 weeks
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
Heat Pain Tolerance
Time Frame: 12 weeks
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
Temporal Pain Summation
Time Frame: 12 weeks
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
Detecting Diffuse Noxious Inhibitory Control (DNIC)
Time Frame: 12 weeks
Subjects will be measured for their Diffuse Noxious Inhibitory Control (DNIC). The testing will be done at 5 of the 6 visits.
12 weeks
Heat Sensation
Time Frame: 12 weeks
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

National Institute on Drug Abuse (NIDA)
National Institutes of Health (NIH)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2013

Primary Completion (Actual)

December 1, 2022

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

August 31, 2012

First Submitted That Met QC Criteria

September 4, 2012

First Posted (Estimate)

September 7, 2012

Study Record Updates

Last Update Posted (Actual)

March 14, 2023

Last Update Submitted That Met QC Criteria

March 13, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013P-001510
  • 1R01DA036564-01 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Chronic Pain

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Hong Kong

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe