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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Massachusetts General Hospital
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jianren Mao, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01681264
First received: August 31, 2012
Last updated: July 2, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention
Chronic Pain
Drug: Guanfacine
Drug: Morphine
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Guanfacine on Opioid-induced Hyperalgesia (OIH) and Tolerance

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Quantitative Sensory Testing (QST) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Quantitative Sensory Testing (QST) results will be used to compare the 5 treatment groups.


Secondary Outcome Measures:
  • Heat Pain Threshold [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Heat Pain Tolerance [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Temporal Pain Summation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Detecting Diffuse Noxious Inhibitory Control (DNIC) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Subjects will be measured for their Diffuse Noxious Inhibitory Control (DNIC). The testing will be done at 5 of the 6 visits.

  • Heat Sensation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Subjects will be measured for their heat sensation using Quantitative Sensory Testing (QST). The testing will be done at 5 of the 6 visits.


Estimated Enrollment: 200
Study Start Date: November 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Morphine:guanfacine

Subjects will be randomized into 1 of the following 5 treatment groups:

  1. morphine: placebo
  2. morphine: guanfacine (1mg)
  3. morphine: guanfacine (2mg)
  4. placebo: guanfacine (2mg)
  5. placebo: placebo

Subjects who are randomized into the guanfacine:morphine groups will be compared to the placebo-mixed or placebo only groups.

Drug: Guanfacine

Subjects will be randomized into 1 of the following 5 treatment groups:

  1. morphine: placebo
  2. morphine: guanfacine (1mg)
  3. morphine: guanfacine (2mg)
  4. placebo: guanfacine (2mg)
  5. placebo: placebo

To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 12 weeks of drug treatment (combination or placebo).

Other Name: Tenex, Intuniv
Drug: Morphine

Subjects will be randomized into 1 of the following 5 treatment groups:

  1. morphine: placebo
  2. morphine: guanfacine (1mg)
  3. morphine: guanfacine (2mg)
  4. placebo: guanfacine (2mg)
  5. placebo: placebo

To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 12 weeks of drug treatment (combination or placebo).

Other Name: MS Contin, MS IR
Placebo Comparator: Placebo

Subjects will be randomized into 1 of the following 5 treatment groups:

  1. morphine: placebo
  2. morphine: guanfacine (1mg)
  3. morphine: guanfacine (2mg)
  4. placebo: guanfacine (2mg)
  5. placebo: placebo

Subjects who are randomized into the guanfacine:morphine groups will be compared to the placebo-mixed or placebo only groups.

Drug: Guanfacine

Subjects will be randomized into 1 of the following 5 treatment groups:

  1. morphine: placebo
  2. morphine: guanfacine (1mg)
  3. morphine: guanfacine (2mg)
  4. placebo: guanfacine (2mg)
  5. placebo: placebo

To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 12 weeks of drug treatment (combination or placebo).

Other Name: Tenex, Intuniv
Drug: Morphine

Subjects will be randomized into 1 of the following 5 treatment groups:

  1. morphine: placebo
  2. morphine: guanfacine (1mg)
  3. morphine: guanfacine (2mg)
  4. placebo: guanfacine (2mg)
  5. placebo: placebo

To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 12 weeks of drug treatment (combination or placebo).

Other Name: MS Contin, MS IR
Drug: Placebo

Subjects will be randomized into 1 of the following 5 treatment groups:

  1. morphine: placebo
  2. morphine: guanfacine (1mg)
  3. morphine: guanfacine (2mg)
  4. placebo: guanfacine (2mg)
  5. placebo: placebo

To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 12 weeks of drug treatment (combination or placebo).

Other Name: Placebo, sugar pill

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • 18-65 years old
  • Chronic neck or back pain condition for at least 6 months
  • VAS score of 4-8
  • Has not taken an opioid for the last 6 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01681264

Contacts
Contact: Trang T Vo, B.A. 617-724-6102 tvo3@partners.org

Locations
United States, Massachusetts
Center for Translational Pain Research Recruiting
Boston, Massachusetts, United States, 02114
Contact: Trang T Vo, B.A.    617-724-6102    tvo3@partners.org   
Principal Investigator: Jianren Mao, M.D., Ph.D.         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Jianren Mao, M.D., Ph.D. Massachusetts General Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Jianren Mao, MD, PhD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01681264     History of Changes
Other Study ID Numbers: 2013P-001510
Study First Received: August 31, 2012
Last Updated: July 2, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Pain
Pain Management

Additional relevant MeSH terms:
Chronic Pain
Hyperalgesia
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Somatosensory Disorders
Sensation Disorders
Morphine
Guanfacine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Antihypertensive Agents
Cardiovascular Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 02, 2014