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

NCT ID: NCT02192398

Last Updated: 2025-11-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2022-10-31

Brief Summary

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

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.

Conditions

Chronic Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Guanfacine

Intervention Type: DRUG

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).

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.

Group Type: ACTIVE_COMPARATOR

Guanfacine

Intervention Type: DRUG

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).

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Tenex, Intuniv; Placebo, sugar pill

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jianren Mao, MD, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jianren Mao, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

MGH Center for Translational Pain Research

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

1R01DA036564-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2014P-001377

Identifier Type: -

Identifier Source: org_study_id