Chronic Low Back Pain, Chronic Neck Pain
Conditions
Keywords
Pain, Pain Management
Brief summary
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.
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.
Interventions
DRUGMorphine
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.
DRUGDuloxetine
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.
DRUGPlacebo
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.
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Opioid Dose (Morphine-equivalent Dose in mg) | 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. |
| Visual Analog Scale (VAS) | 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. |
Countries
United States
Participant flow
Recruitment details
Recruitment goal was not met by the planned completion time.
Pre-assignment details
81 participants were consented to this study. 22 were not randomized to one of 3 groups as they were deemed ineligible to continue or withdrew from the study. 59 were randomized to 1 of 3 groups. 28 of which completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Morphine, Duloxetine Subjects will take a maximum dose of 60 mg/day of extended release morphine capsules and 60 mg of duloxetine capsules.
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.
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. | 21 |
| Morphine, Placebo Duloxetine Subjects will take a maximum dose of 60 mg/day of extended release morphine capsules and placebo duloxetine capsules.
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.
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. | 19 |
| Placebo Morphine, Duloxetine Subjects will take placebo morphine capsules and 60 mg of duloxetine capsules.
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.
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. | 19 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | COVID-19 pandemic shutdown | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 | 4 |
| Overall Study | Physician Decision | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 6 | 5 | 7 |
Baseline characteristics
| Characteristic | Morphine, Duloxetine | Morphine, Placebo Duloxetine | Placebo Morphine, Duloxetine | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 3 Participants | 2 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 16 Participants | 17 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 1 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 15 Participants | 17 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 5 Participants | 7 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 13 Participants | 10 Participants | 8 Participants | 31 Participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 6 Participants | 19 Participants |
| Sex: Female, Male Male | 14 Participants | 13 Participants | 13 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 19 | 0 / 19 |
| other Total, other adverse events | 0 / 21 | 0 / 19 | 0 / 19 |
| serious Total, serious adverse events | 0 / 21 | 0 / 19 | 0 / 19 |
Outcome results
Primary
Overall Opioid Dose (Morphine-equivalent Dose in mg)
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.
Time frame: 10 weeks
Population: The data collection was incomplete for the subjects who completed the study, therefore, the summary can not be provided. The total number of participants needed for analysis was not reached, and the results information provided are regarding the subjects who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Morphine, Duloxetine | Overall Opioid Dose (Morphine-equivalent Dose in mg) | 19.6 mg | Standard Deviation 2.05 |
| Morphine, Placebo Duloxetine | Overall Opioid Dose (Morphine-equivalent Dose in mg) | 19.6 mg | Standard Deviation 2.16 |
| Placebo Morphine, Duloxetine | Overall Opioid Dose (Morphine-equivalent Dose in mg) | 19.6 mg | Standard Deviation 2.16 |
Primary
Visual Analog Scale (VAS)
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.
Time frame: 10 weeks
Population: The data collection was incomplete for the subjects who completed the study, therefore, the summary and outcome can not be provided. The total number of participants needed for analysis was not reached, and the results information provided are regarding the subjects who completed the study. Due to the total number of participants needed for analysis not being met, the summary can not be provided.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Morphine, Duloxetine | Visual Analog Scale (VAS) | 2.8 cm | Standard Deviation 3.05 |
| Morphine, Placebo Duloxetine | Visual Analog Scale (VAS) | 2.33 cm | Standard Deviation 3.05 |
| Placebo Morphine, Duloxetine | Visual Analog Scale (VAS) | 4.66 cm | Standard Deviation 3.05 |