Effect of Combined Morphine and Duloxetine on Chronic Pain (Duloxetine)

November 8, 2024 updated by: Jianren Mao, MD, PhD, Massachusetts General Hospital
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

81

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Karina de Sousa

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Morphine, Duloxetine
Subjects will take a maximum dose of 60 mg/day of extended release morphine capsules and 60 mg of duloxetine capsules.
Drug: Morphine
Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.
Other Names:
  • Morphine Sulfate Contin, Morphine Sulfate Instant Release
Drug: Duloxetine
Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.
Other Names:
  • Cymbalta
Placebo Comparator: Morphine, Placebo Duloxetine
Subjects will take a maximum dose of 60 mg/day of extended release morphine capsules and placebo duloxetine capsules.
Drug: Morphine
Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.
Other Names:
  • Morphine Sulfate Contin, Morphine Sulfate Instant Release
Drug: Placebo
Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.
Other Names:
  • Sugar pill
Placebo Comparator: Placebo Morphine, Duloxetine
Subjects will take placebo morphine capsules and 60 mg of duloxetine capsules.
Drug: Duloxetine
Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.
Other Names:
  • Cymbalta
Drug: Placebo
Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.
Other Names:
  • Sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Opioid Dose (Morphine-equivalent Dose in mg)
Time Frame: 10 weeks
The investigators will compare overall opioid dose (in morphine-equivalent dose in mg) between the morphine/duloxetine group and the morphine/placebo group and compare rescue dose among all three groups. The higher overall opioid dose, the more consumption of opioid.
10 weeks
Visual Analog Scale (VAS)
Time Frame: 10 weeks
To examine changes in pain intensity measured on a Visual Analog Scale with units on a scale ranging from 0 cm-10 cm (0 cm being lowest and 10 cm being the higher the score, where values closer to 10 cm reflect more pain) and to determine total versus rescue opioid use after each treatment.
10 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Investigators

  • Principal Investigator: Jianren Mao, MD, PhD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 12, 2018

Primary Completion (Actual)

April 5, 2022

Study Completion (Actual)

April 5, 2022

Study Registration Dates

First Submitted

August 11, 2017

First Submitted That Met QC Criteria

August 11, 2017

First Posted (Actual)

August 15, 2017

Study Record Updates

Last Update Posted (Estimated)

November 14, 2024

Last Update Submitted That Met QC Criteria

November 8, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017P001589

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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