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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

August 31, 2012
July 2, 2014
November 2013
December 2016   (final data collection date for primary outcome measure)
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.
Quantitative Sensory Testing [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
QST results will be used to compare the 5 treatment groups.
Complete list of historical versions of study NCT01681264 on ClinicalTrials.gov Archive Site
  • 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.
  • Heat Pain Threshold [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    We will measure the heat pain threshold using the QST. The testing will be done at three of the four visits.
  • Heat Pain Tolerance [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    We will measure the heat pain tolerance using the QST. The testing will be done at three of the four visits.
  • Temporal Pain Summation [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    We will measure the temporal pain summation using the QST. The testing will be done at three of the four visits.
  • Detecting DNIC [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    We will detect the DNIC using the QST. The testing will be done at three of the four visits.
  • Needle Stick Test [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    We will measure the subject's pain score before and after the subcutaneous needle stick. The testing will be done at three of the four visits.
Not Provided
Not Provided
 
Effect of Guanfacine on Opioid-induced Hyperalgesia (OIH) and Tolerance
Effect of Guanfacine on Opioid-induced Hyperalgesia (OIH) and Tolerance

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

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Chronic Pain
  • 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
  • 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.

    Interventions:
    • Drug: Guanfacine
    • Drug: Morphine
  • 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.

    Interventions:
    • Drug: Guanfacine
    • Drug: Morphine
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
200
December 2017
December 2016   (final data collection date for primary outcome measure)

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.
Both
18 Years to 65 Years
No
Contact: Trang T Vo, B.A. 617-724-6102 tvo3@partners.org
United States
 
NCT01681264
2013P-001510
Yes
Jianren Mao, MD, PhD, Massachusetts General Hospital
Massachusetts General Hospital
National Institutes of Health (NIH)
Principal Investigator: Jianren Mao, M.D., Ph.D. Massachusetts General Hospital
Massachusetts General Hospital
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP