Chronic PainPhase 4NCT01681264

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

A Phase 4 study testing Morphine, Guanfacine 1mg and Guanfacine 2mg in people with Chronic Pain, run by Massachusetts General Hospital at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Dual medication (guanfacine and morphine) as a standard treatment for chronic pain. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Chronic Pain
What is being tested?: Morphine, Guanfacine 1mg and Guanfacine 2mg
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 137 participants
Where: 1 siteUnited States
Study dates: Sep 2014to Dec 2023
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 17Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Center for Translational Pain Research
Boston, Massachusetts, 02114

Other trials in United States

About this study

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

Read the 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.

Conditions: Chronic Pain
Being tested: Morphine, Guanfacine 1mg, Guanfacine 2mg, Placebo
Keywords: Pain, Pain Management, Back pain, Neck pain
Medical subject headings: Chronic Pain, Pain, Agnosia, Back Pain, Neck Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MorphineDrug
Also called MS Contin
Guanfacine 1mgDrug
Also called Intuniv, Tenex
Guanfacine 2mgDrug
Also called Intuniv, Tenex
PlaceboDrug
Also called Sugar Pill

Study groups in NCT01681264
Study group	Role	What they receive
Morphine:Placebo	Active comparator	Not described Receives: Drug: Morphine; Drug: Placebo
Morphine:Guanfacine 1mg	Active comparator	Not described Receives: Drug: Morphine; Drug: Guanfacine 1mg
Morphine:Guanfacine 2mg	Active comparator	Not described Receives: Drug: Morphine; Drug: Guanfacine 2mg
Placebo:Guanfacine 2mg	Active comparator	Not described Receives: Drug: Guanfacine 2mg; Drug: Placebo
Placebo:Placebo	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Numeric Pain Score
Change in numeric pain score (from 0-10: 0 being no pain; 10 being worst pain) was used to measure changes in pain.
Measured: 12 weeks; outcomes were assessed at the baseline and 12 weeks.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2014Dec 2023

First posted7 Sep 2012 (estimated)
Study startSep 2014
Primary completionDec 2022
Study completionDec 2023

Why it stopped: End of NIH funding

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Chronic PainStudies of the same condition, open and under way.
More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 137 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01681264
Sponsor's protocol ID: 2013P-001510
Other IDs: 1R01DA036564-01
Status last verified: Jul 2026
First submitted: 31 Aug 2012
Last updated: 31 Jul 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Chronic Pain trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of Guanfacine on Opioid-induced Hyperalgesia (OIH) and Tolerance
ClinicalTrials.gov ID: NCT01681264
Acronym / sponsor ID: 2013P-001510
Conditions: Chronic Pain
Keywords: Pain, Pain Management, Back pain, Neck pain
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: End of NIH funding
Enrolment: 137 participants (actual)
Lead sponsor: Massachusetts General HospitalUniversity, hospital or other
Collaborators: National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA)
Study start: Sep 2014 (actual)
Primary completion: Dec 2022 (actual)
Study completion: Dec 2023 (actual)
First posted: 7 Sep 2012 (estimated)
Results: Posted 31 Jul 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 5

Arm	Type	Receives
Morphine:Placebo	Active comparator	Drug: Morphine, Drug: Placebo
Morphine:Guanfacine 1mg	Active comparator	Drug: Morphine, Drug: Guanfacine 1mg
Morphine:Guanfacine 2mg	Active comparator	Drug: Morphine, Drug: Guanfacine 2mg
Placebo:Guanfacine 2mg	Active comparator	Drug: Guanfacine 2mg, Drug: Placebo
Placebo:Placebo	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (17 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MorphineAlso: MS Contin	Drug	Morphine:Guanfacine 1mg, Morphine:Guanfacine 2mg, Morphine:Placebo
Guanfacine 1mgAlso: Intuniv, Tenex	Drug	Morphine:Guanfacine 1mg
Guanfacine 2mgAlso: Intuniv, Tenex	Drug	Morphine:Guanfacine 2mg, Placebo:Guanfacine 2mg
PlaceboAlso: Sugar Pill	Drug	Morphine:Placebo, Placebo:Guanfacine 2mg, Placebo:Placebo

Primary outcome

Numeric Pain Score
Time frame: 12 weeks; outcomes were assessed at the baseline and 12 weeks.
Change in numeric pain score (from 0-10: 0 being no pain; 10 being worst pain) was used to measure changes in pain.

Results and safety

Results posted to the registry on 31 Jul 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Morphine:Placebo	28	10
Morphine:Guanfacine 1mg	29	11
Morphine:Guanfacine 2mg	28	11
Placebo:Guanfacine 2mg	26	10
Placebo:Placebo	26	9

Primary outcome: Numeric Pain Score

Time frame: 12 weeks; outcomes were assessed at the baseline and 12 weeks.. Mean (Standard Deviation). Unit: score on a scale

Measure	Morphine/Placebo n = 10	Morphine/Guanfacin 1 mg n = 11	Morphine/Guanfacin 2 mg n = 11	Placebo/Guanfacin 2 mg n = 10	Placebo/Placebo n = 9
Value	4.1 (3.7)	3.9 (3.6)	3.7 (3.5)	4.3 (3.8)	4.7 (3.9)

Population analysed: Study participants enrolled in five study groups

Adverse events

Time frame: 5 years. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Morphine:Placebo	0 of 28 (0%)	0 of 28 (0%)	0 of 28
Morphine:Guanfacine 1mg	0 of 29 (0%)	0 of 29 (0%)	0 of 29
Morphine:Guanfacine 2mg	0 of 28 (0%)	0 of 28 (0%)	0 of 28
Placebo:Guanfacine 2mg	0 of 26 (0%)	0 of 26 (0%)	0 of 26
Placebo:Placebo	0 of 26 (0%)	0 of 26 (0%)	0 of 26

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Center for Translational Pain ResearchLink provided by the sponsor.

Related trials for Chronic Pain

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Not yet recruiting
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jianren Mao, M.D., Ph.D. principal investigator

Massachusetts General Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Morphine, Guanfacine 1mg and Guanfacine 2mg in people with Chronic Pain, run by Massachusetts General Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Numeric Pain Score (time frame: 12 weeks; outcomes were assessed at the baseline and 12 weeks.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01681264.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.