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

January 2, 2024 updated by: Jianren Mao, MD, PhD, Massachusetts General Hospital
Combination of guanfacine with opioid medication 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 reverse Opioid-Induced Hyperalgesia (OIH) when combined with opioids in chronic pain management.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Not Applicable

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
        • MGH 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

Description

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.

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: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Guanfacine (2mg)

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.
Drug: Guanfacine

Subjects will be randomized into 1 of the following 3 treatment groups:

  1. guanfacine (2mg)
  2. guanfacine (1mg)
  3. placebo

To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 4 weeks of drug treatment (guanfacine or placebo).

Other Names:
  • Tenex, Intuniv
Active Comparator: Guanfacine (1mg)

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.
Drug: Guanfacine

Subjects will be randomized into 1 of the following 3 treatment groups:

  1. guanfacine (2mg)
  2. guanfacine (1mg)
  3. placebo

To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 4 weeks of drug treatment (guanfacine or placebo).

Other Names:
  • Tenex, Intuniv
Placebo Comparator: Placebo

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.
Drug: Placebo

Subjects will be randomized into 1 of the following 3 treatment groups:

  1. guanfacine (2mg)
  2. guanfacine (1mg)
  3. placebo To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 4 weeks of drug treatment (guanfacine or placebo).
Other Names:
  • Placebo, sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quantitative Sensory Testing (QST)
Time Frame: 4 weeks
Quantitative Sensory Testing (QST) results will be used to compare the 3 treatment groups.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Heat Pain Threshold
Time Frame: 4 weeks
Subjects will be measured for their heat pain threshold using QST. The testing will be done at 3 of the 4 visits.
4 weeks
Heat Pain Tolerance
Time Frame: 4 weeks
Subjects will be measured for their heat pain tolerance using QST. The testing will be done at 3 of the 4 visits.
4 weeks
Temporal Pain Summation
Time Frame: 4 weeks
Subjects will be measured for their temporal pain summation using QST. The testing will be done at 3 of the 4 visits.
4 weeks
Detecting Diffuse Noxious Inhibitory Control (DNIC)
Time Frame: 4 weeks
Subjects will be measured for their Diffuse Noxious Inhibitory Control (DNIC). The testing will be done at 3 of the 4 visits.
4 weeks
Heat Sensation
Time Frame: 4 weeks
Subjects will be measured for their heat sensation using QST. The testing will be done at 3 of the 4 visits.
4 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)

Investigators

  • Principal Investigator: Jianren Mao, M.D., Ph.D., Massachusetts General Hospital

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

September 1, 2014

Primary Completion (Actual)

December 1, 2022

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

July 15, 2014

First Submitted That Met QC Criteria

July 15, 2014

First Posted (Estimated)

July 16, 2014

Study Record Updates

Last Update Posted (Actual)

January 5, 2024

Last Update Submitted That Met QC Criteria

January 2, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2014P-001377
  • 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 Guanfacine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Tanzania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe