Back Pain
Conditions
Keywords
chronic pain, back pain, antidepressants
Brief summary
This 12 week placebo controlled clinical trial tests the individual and combined effects of an antidepressant medication and cognitive behavioral therapy for chronic back pain.
Detailed description
This is a 4 arm 12 week randomized clinical trial comparing the efficacy of 1) low concentration desipramine (\< 60 ng/ml); 2) cognitive behavioral therapy; 3) low concentration desipramine + cognitive behavioral therapy; and 4) placebo medication (benzotropine mesylate).
Interventions
BEHAVIORALcognitive behavioral therapy
cognitive behavioral therapy, a type of psychotherapy oriented towards restoring function and reducing impact of pain on everyday life
desipramine hydrochloride, with dose targeted to achieve a serum concentration of 5-60ng/ml
DRUGbenztropine mesylate 0.125 mg daily
benztropine mesylate is a placebo, some of whose side effects mimic those of experimental intervention, desipramine hydrochloride
Sponsors
University of California, San Diego
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Chronic back pain (daily pain for \> 6 months)
Exclusion criteria
* Major medical conditions which might contraindicate antidepressant treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intent-toTreat Analysis of Descriptor Differential Scale (DDS) of Pain Intensity | 12 weeks after baseline (or last observation carried forward) | The DDS is self-report measure of current pain intensity of chronic back pain. Participants rate pain on a 20 point scale as being greater or less intense relative to 12 adjectival descriptor words which serve as anchors (eg, greater or less than faint, moderate, strong). Scores range from 0 to 20 with higher scores indicating higher pain intensity. The analysis evaluated the 'as randomized' sample at 12 weeks after baseline or last observation carried forward, after co-varying for baseline (pre-treatment) values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Roland and Morris Disability Questionnaire | 12 weeks after baseline (or last observation carried forward) | This questionnaire measures disability in everyday function due to back pain. It is a 24-item checklist asking patients to endorse whether or not back pain limits activities they normally do (eg, I stay at home most of the time because of my back). Scores range from 0 to 24, with higher scores indicating greater disability in everyday function due to back pain. The analysis evaluated the 'as randomized' sample at 12 weeks after baseline, after co-varying for baseline (pre-treatment) values. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 desipramine hydrochloride
desipramine hydrochloride: desipramine hydrochloride, with dose targeted to achieve a serum concentration of 5-60ng/ml | 37 |
| Arm 2 cognitive behavioral therapy
cognitive behavioral therapy: cognitive behavioral therapy, a type of psychotherapy oriented towards restoring function and reducing impact of pain on everyday life | 33 |
| Arm 3 desipramine hydrochloride and cognitive behavioral therapy
desipramine hydrochloride: desipramine hydrochloride, with dose targeted to achieve a serum concentration of 5-60ng/ml
cognitive behavioral therapy: cognitive behavioral therapy, a type of psychotherapy oriented towards restoring function and reducing impact of pain on everyday life | 37 |
| Arm 4 anticholinergic medication; active placebo
benztropine mesylate 0.125 mg daily: benztropine mesylate is a placebo, some of whose side effects mimic those of experimental intervention, desipramine hydrochloride | 32 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 5 | 2 |
| Overall Study | Lost to Follow-up | 2 | 2 | 6 | 4 |
| Overall Study | Protocol Violation | 0 | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 2 | 5 | 3 |
Baseline characteristics
| Characteristic | Arm 3 | Total | Arm 1 | Arm 2 | Arm 4 |
|---|---|---|---|---|---|
| Age, Continuous | 51.5 years STANDARD_DEVIATION 13.7 | 55.8 years STANDARD_DEVIATION 11.7 | 56.5 years STANDARD_DEVIATION 11.7 | 57.8 years STANDARD_DEVIATION 9.2 | 57.9 years STANDARD_DEVIATION 10.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 25 Participants | 6 Participants | 10 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 103 Participants | 29 Participants | 22 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 11 Participants | 2 Participants | 1 Participants | 4 Participants |
| Gender Female | 3 Participants | 15 Participants | 5 Participants | 4 Participants | 3 Participants |
| Gender Male | 34 Participants | 123 Participants | 32 Participants | 29 Participants | 28 Participants |
| Pain Intensity and Back Pain Disability Back Pain Disability (Roland and Morris) | 11.7 units on a scale STANDARD_DEVIATION 5.4 | 11.8 units on a scale STANDARD_DEVIATION 4.9 | 8.7 units on a scale STANDARD_DEVIATION 5.4 | 13.0 units on a scale STANDARD_DEVIATION 4.3 | 12.6 units on a scale STANDARD_DEVIATION 3.8 |
| Pain Intensity and Back Pain Disability Pain Intensity (Descriptor Differential Scale) | 11.9 units on a scale STANDARD_DEVIATION 5.1 | 11.4 units on a scale STANDARD_DEVIATION 4 | 9.9 units on a scale STANDARD_DEVIATION 4.9 | 11.9 units on a scale STANDARD_DEVIATION 4.3 | 12.1 units on a scale STANDARD_DEVIATION 4.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 5 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 21 Participants | 6 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 16 Participants | 4 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 7 Participants | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 21 Participants | 84 Participants | 25 Participants | 18 Participants | 20 Participants |
| Region of Enrollment United States | 37 participants | 139 participants | 37 participants | 33 participants | 32 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 17 | 8 / 20 | 7 / 16 | 6 / 17 |
| serious Total, serious adverse events | 1 / 38 | 0 / 34 | 1 / 37 | 0 / 33 |
Outcome results
Primary
Intent-toTreat Analysis of Descriptor Differential Scale (DDS) of Pain Intensity
The DDS is self-report measure of current pain intensity of chronic back pain. Participants rate pain on a 20 point scale as being greater or less intense relative to 12 adjectival descriptor words which serve as anchors (eg, greater or less than faint, moderate, strong). Scores range from 0 to 20 with higher scores indicating higher pain intensity. The analysis evaluated the 'as randomized' sample at 12 weeks after baseline or last observation carried forward, after co-varying for baseline (pre-treatment) values.
Time frame: 12 weeks after baseline (or last observation carried forward)
Population: We conducted an intent-to-treat analysis of all randomized participants assigned to desipramine or to active drug placebo (benztropine) comparing mean DDS pain intensity at Week 12 (or the last observation carried forward) adjusted for mean baseline score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 + Arm 3 | Intent-toTreat Analysis of Descriptor Differential Scale (DDS) of Pain Intensity | 8.3 units on a scale | Standard Error 0.5 |
| Arm 2 + Arm 4 | Intent-toTreat Analysis of Descriptor Differential Scale (DDS) of Pain Intensity | 8.1 units on a scale | Standard Error 0.6 |
Comparison: In an intent-to-treat analysis of all randomized participants assigned to experimental drug (desipramine) or active placebo (benztropine) an analysis of variance compared mean Descriptor Differential Scale scores at 12 weeks (or last observation carried forward) adjusted fro mean baseline score ( = ).p-value: 0.7ANCOVA
Primary
Intent-toTreat Analysis of Descriptor Differential Scale (DDS) of Pain Intensity
The DDS is self-report measure of current pain intensity of chronic back pain. Participants rate pain on a 20 point scale as being greater or less intense relative to 12 adjectival descriptor words which serve as anchors (eg, greater or less than faint, moderate, strong). Scores range from 0 to 20 with higher scores indicating higher pain intensity. The analysis evaluated the 'as randomized' sample at 12 weeks after baseline or last observation carried forward, after co-varying for baseline (pre-treatment) values.
Time frame: 12 weeks after baseline (or last observation carried forward)
Population: We conducted an intent-to-treat analysis of all randomized participants assigned to cognitive behavioral therapy to or no behavior therapy comparing mean DDS pain intensity at Week 12 (or the last observation carried forward) adjusted for mean baseline score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 + Arm 3 | Intent-toTreat Analysis of Descriptor Differential Scale (DDS) of Pain Intensity | 8.0 units on a scale | Standard Error 0.6 |
| Arm 2 + Arm 4 | Intent-toTreat Analysis of Descriptor Differential Scale (DDS) of Pain Intensity | 8.4 units on a scale | Standard Error 0.6 |
p-value: 0.6ANCOVA
Secondary
Roland and Morris Disability Questionnaire
This questionnaire measures disability in everyday function due to back pain. It is a 24-item checklist asking patients to endorse whether or not back pain limits activities they normally do (eg, I stay at home most of the time because of my back). Scores range from 0 to 24, with higher scores indicating greater disability in everyday function due to back pain. The analysis evaluated the 'as randomized' sample at 12 weeks after baseline, after co-varying for baseline (pre-treatment) values.
Time frame: 12 weeks after baseline (or last observation carried forward)
Population: All participants assigned at baseline to receive desipramine hydrochloride or benztropine mesylate (drug effect). This is an 'as randomized' Intent-to-Treat analysis. Values are mean scores at Week 12 (or last observation carried forward). Means are adjusted for baseline Roland and Morris scores
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 + Arm 3 | Roland and Morris Disability Questionnaire | 8.7 Units on a scale. | Standard Error 0.5 |
| Arm 2 + Arm 4 | Roland and Morris Disability Questionnaire | 8.9 Units on a scale. | Standard Error 0.5 |
Comparison: In the intent-to-treat sample of all randomized participants assigned to experimental drug (desipramine) or active placebo (benztropine) an analysis of variance (ANOVA) compared mean Roland and Morris scores at 12 weeks adjusted for mean baseline scores.p-value: 0.84ANCOVA
Secondary
Roland and Morris Disability Questionnaire
This questionnaire measures disability in everyday function due to back pain. It is a 24-item checklist asking patients to endorse whether or not back pain limits activities they normally do (eg, I stay at home most of the time because of my back). Scores range from 0 to 24, with higher scores indicating greater disability in everyday function due to back pain. The analysis evaluated the 'as randomized' sample at 12 weeks after baseline, after co-varying for baseline (pre-treatment) values.
Time frame: 12 weeks after baseline (or last observation carried forward)
Population: All participants assigned at baseline to receive cognitive behavioral therapy or to no cognitive behavioral therapy (behavioral effect). This is an 'as randomized' Intent-to-Treat analysis. Values are mean scores at Week 12 (or last observation carried forward). Means are adjusted for baseline Roland and Morris scores
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 + Arm 3 | Roland and Morris Disability Questionnaire | 8.7 Units on a scale. | Standard Error 0.5 |
| Arm 2 + Arm 4 | Roland and Morris Disability Questionnaire | 8.9 Units on a scale. | Standard Error 0.5 |
Comparison: This analysis compares outcomes for participants assigned at baseline to receive cognitive behavioral therapy or not to receive cognitive behavioral therapy (behavioral effect)p-value: 0.8ANCOVA