Effect of Combined Morphine and Duloxetine on Chronic Pain

Mass General Brigham

Status and phase: Completed; Phase 4

Conditions: Chronic Low Back Pain; Chronic Neck Pain

Treatments: Drug: Morphine; Drug: Duloxetine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03249558

2017P001589

Details and patient eligibility

About

A double-blind, randomized, and placebo-controlled clinical study examining whether duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), could enhance opioid analgesia and reduce overall opioid use. Positive outcomes will help improve the overall effectiveness of clinical opioid therapy and reduce unnecessary opioid dose escalation.

Full description

Subjects will participate in a 10-week study consisting of three phases: Phase I is the dose titration period of 4 weeks, Phase II is the dose maintenance period of 4 weeks, and Phase III is the dose taper period of 2 weeks. Seven office visits (Initial visit/baseline, weeks 1, 3, 5, 7, 9, and end of week 10) and four follow up phone calls (weeks 2, 4, 6, and 10) will be used to collect data. Since this is a prospective study, we will be able to first determine baseline QST and VAS pain score, followed by assessing their longitudinal changes at each office visit. To assess OIH, QST will be performed at each office visit before subject takes the next dose of the study drugs. We will also measure plasma morphine concentration during the titration and maintenance phase to help validate morphine intake.

Enrollment: 81 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Subject is 18-70 years old.
2. Subject has chronic neck or back pain for at least 3 months.
3. Subject has a VAS ≥ 5.
4. Has not taken duloxetine in the last 3 months.
5. Has not taken an opioid in the last 3 months, but has taken one in the past without sufficient pain control OR has never taken opioids but has failed at 3 (or more) non-opioid treatments.

Exclusion criteria

1. Subject has major psychiatric disorders requiring recent hospitalization (within 3 months) such as major depression, bipolar disorder, schizophrenia, anxiety disorder, or psychotic disorder.
2. Subject is using illicit drugs detected by urine toxicology/drug screen.
3. Subject is pregnant or lactating/breast feeding.
4. Subject is allergic to morphine or duloxetine.
5. Subject is on an antidepressant including serotonin-norepinephrine reuptake inhibitors (SNRI), selective serotonin reuptake inhibitor (SSRI), tricyclic antidepressant.
6. Subject has a history of suicidal attempts or current suicidal ideation.
7. Subject takes monoamine oxidase inhibitors, antipsychotics, triptan drugs such as sumatriptan, lithium, linezolid, tramadol (Ultram), St. John's Wort, central nervous system (CNS) stimulants such as amphetamine, methylphenidate, methamphetamine, phentermine, diethylpropion, sibutramine, cocaine, or thioridazine.
8. Subject has uncontrolled narrow-angle glaucoma.
9. Subject has sensory deficits on arms or Raynaud's Syndrome.
10. Subject has a pending litigation related to chronic pain condition.
11. Subject is on methadone or suboxone treatment for addiction.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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81 participants in 3 patient groups, including a placebo group

Morphine, Duloxetine

Active Comparator group

Description:

Subjects will take a maximum dose of 60 mg/day of extended release morphine capsules and 60 mg of duloxetine capsules.

Treatment:

Drug: Duloxetine

Drug: Morphine

Morphine, Placebo Duloxetine

Placebo Comparator group

Description:

Subjects will take a maximum dose of 60 mg/day of extended release morphine capsules and placebo duloxetine capsules.

Treatment:

Drug: Placebo

Drug: Morphine

Placebo Morphine, Duloxetine

Placebo Comparator group

Description:

Subjects will take placebo morphine capsules and 60 mg of duloxetine capsules.

Treatment:

Drug: Placebo

Drug: Duloxetine