Chronic Pain
Conditions
Keywords
Chronic Low Back Pain
Brief summary
Chronic Pain (CP) management has increasingly utilized long-term opioid analgesic therapy, a change associated with increased opioid abuse (via greater exposure in vulnerable individuals), non-pain health consequences (hormone changes, falls), and a dramatic rise in opioid-related overdoses and deaths. Treatment strategies that minimize the need for chronic high-dose opioids are sorely needed. This project will test the novel hypothesis that effective pain relief can be achieved at lower opioid analgesic doses by increasing levels of endogenous opioids (EOs).
Detailed description
There are three separate goals of the study: 1) test the effects of the intervention (versus control) on clinical outcomes, 2) test for endogenous opioid mechanisms of the intervention (indexed by the difference in laboratory evoked pain response between placebo and naloxone drug conditions), and 3) test the effects of the intervention on morphine responses (indexed by the difference in evoked pain response between placebo and morphine laboratory drug conditions). This project will determine whether enhancing endogenous opioids (via aerobic exercise training) permits achieving desired levels of analgesia with lower dosages of opioid analgesics, and fewer side effects and abuse-relevant drug effects. This 4 year project will test study hypotheses in a sample of 116 chronic low back pain patients. The study will have two key elements: 1) a randomized, controlled aerobic exercise manipulation in CP patients completing daily electronic pain diaries and 2) laboratory evoked thermal pain protocols pre- and post-exercise permitting direct examination of changes in both opioid analgesic effects (in response to a series of incremental morphine doses) and EO activity (indexed by comparing pain responses after placebo vs. opioid blockade). The study will use a 6 week supervised aerobic exercise manipulation, with subjects randomly assigned to the exercise protocol or a no exercise control condition. The study will employ a mixed between/within-subjects design using double-blind, counterbalanced, placebo-controlled administration of both an opioid antagonist (naloxone) and an opioid agonist (morphine). All participants will undergo three identical laboratory pain-induction sessions (each ≈5 days apart) prior to randomization to experimental condition, and again at the end of the 6 week exercise manipulation period (regardless of exercise group assignment) during which they will receive the 3 study drugs and participate in controlled laboratory evaluation of evoked thermal pain responsiveness.
Interventions
BEHAVIORAL6 week aerobic exercise intervention
Participants randomly assigned to the 6 week aerobic exercise intervention will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks). Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise will be progressively increased up to target during the first two weeks to avoid symptom exacerbation and minimize study drop-out.
DRUGPlacebo
In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
DRUGMorphine
In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
DRUGnaloxone
In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
Sponsors
National Institute on Drug Abuse (NIDA)
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Intact cognitive status and ability to provide informed consent * Ability to read and write in English sufficiently to understand and complete study questionnaires * Age 18-55 inclusive * Presence of persistent daily low back pain of at least three months duration and of at least a 3/10 in average intensity
Exclusion criteria
* Engagement in \> 2 days/wk and \> 60 min/wk of moderate or vigorous intensity activity based on responses to 6 validated survey questions at screening (CDC BRFSS) * History of renal or hepatic dysfunction * Current or past alcohol or substance dependence * A history of PTSD, psychotic, or bipolar disorders * Chronic pain due to malignancy (e.g., cancer), autoimmune disorders (e.g., rheumatoid arthritis, lupus), or fibromyalgia * Recent daily opiate use * Use of any opioid analgesic medications within 72 hours of study participation (confirmed through rapid urine screening conducted prior to study participation) * Females who are pregnant * History of cardiovascular disease (including myocardial infarction) * History of seizure disorder * Prior allergic reaction/intolerance to morphine or its analogs * Presence of cardiac disease or any other medical condition that would make engaging in the aerobic exercise manipulation unsafe
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean of the Change in Morphine Dosage (in mg) Required to Achieve 25% Reduction in Thermal Evoked Pain Responses Relative to Baseline (Pre-intervention) Placebo Condition Responses | At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later) | At a laboratory testing day pre and post intervention each participant received morphine sulphate (0.3mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02 mg/kg each with testing for thermal evoked pain response. Weight adjusted dosing was used by multiplying the weight of each patient in kg by 0.3mg (dose 1 only) or by .02mg (doses 2-4), with all doses infused in 20mL saline vehicle. Mean of the change in morphine dosage required to achieve 25 % reduction in thermal evoked pain responses on testing day at baseline (pre-intervention) and post intervention. Positive values for the change in the mean between pre and post intervention indicated decreased morphine requirements post intervention. |
| Mean Change in 5-day Electronic Diary Ratings of Low Back Pain Intensity | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) | Mean change in 5-day electronic diary ratings of low back pain intensity from pre intervention baseline to post intervention. 9 point pain scale assessing pain intensity with 0 represents no pain and 8 represents worst possible pain. Positive values indicate reduced pain post intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in McGill Pain Questionnaire-2 Total Chronic Back Pain Ratings | At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later) | Mean change in McGill Pain Questionnaire-2 total chronic back pain ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-10 where 0 represents no pain and 10 represents most intense pain. Positive values indicate decreased back pain post intervention. |
| Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for McGill Pain Questionnaire-2 Total Ratings of Back Pain. | At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later) | Between-participant (aerobic exercise vs. control group) comparison of mean changes from pre- to post-intervention in opioid blockade effects for McGill Pain Questionnaire-2 Total ratings of back pain based on 3 laboratory testing days at baseline (pre intervention) and post intervention. The score ranges from 0-10 where 0 represents no pain and 10 represents most intense pain. Positive values indicate increased endogenous opioid analgesia post intervention. This measure will test the effects of the exercise (versus control) intervention on clinical outcomes as indexed by changes in opioid blockade effects (the difference in laboratory evoked pain response evoked between placebo and naloxone drug conditions). This is a mixed within-between subject design. Per the study protocol, the intent of outcome measures 4 and 6 was to capture opioid blockade effects (within-participant placebo-naloxone condition difference scores) at both the pre- and post-intervention lab assessments, an |
| Mean Change in Positive and Negative Affect Scale-Negative Affect Subscale Ratings. | At pre intervention baseline and again post-intervention (an expected average of 6 weeks later) | Mean change in Positive and Negative Affect Scale-Negative Affect subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. . Scale ratings range from 10 to 50 where 10 represents lowest negative affect possible and 50 represents highest negative affect possible. Positive values indicate decreased negative affect post intervention. |
| Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Euphoria Subscale Ratings | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) | Mean change in morphine condition VAS Opioid Effects-Euphoria subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-300 where 0 means no euphoria and 300 means most euphoria possible. Positive values indicate decreased euphoria post intervention. |
| Mean Change in Placebo Condition Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form | At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later) | Mean change in placebo condition ratings of acute thermal pain intensity using the McGill Pain Questionnaire-Short Form on 3 testing days at baseline (per intervention) and post intervention. The score ranges from 0-33 where 0 represents no pain and 33 represents most intense pain. Positive change values indicate decreased pain responsiveness post intervention. |
| Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects - Unpleasantness Subscale Ratings | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) | Mean change in morphine condition VAS Opioid Effects - Unpleasantness subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-300 where 0 represents no unpleasantness and 300 represents most unpleasantness possible. Positive values indicate decreased unpleasantness post intervention. |
| Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Effect Subscale Ratings | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) | Mean change in morphine condition Drug Effects, Liking, and Take Again (DELTA) -Drug Effect subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 1-5 where 1 represents no effect and 5 represents very strong effect. Positive values indicate decreased overall drug effects post intervention. |
| Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Liking Subscale Ratings | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) | Mean change in morphine condition Drug Effects, Liking, and Take Again (DELTA) -Drug Liking subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-100 where 0 represents dislike a lot and 100 represents like a lot. Positive values indicate decreased drug liking post intervention. |
| Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Take Again Subscale Ratings | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) | Mean change in morphine condition Drug Effects, Liking, and Take Again (DELTA) -Take Again subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-100 where 0 represents definitely would not take again and 100 represents definitely would take again. Positive values indicate decreased desire to take the drug again post intervention. |
| Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Sedation Subscale Ratings | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) | Mean change in morphine condition VAS Opioid Effects-Sedation subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-300 where 0 means no sedation and 300 means most sedation possible. Positive values indicate decreased sedation post intervention. |
| Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form | At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later) | Between-participant (aerobic exercise vs. control group) comparison of mean changes from pre- to post-intervention in opioid blockade effects for ratings of acute thermal pain intensity on the McGill Pain Questionnaire-Short Form based on 3 laboratory testing days at baseline (pre-intervention) and post intervention. The score ranges from 0-33 where 0 represents no pain and 33 represents more intense pain. Positive values indicate increased endogenous opioid analgesia post intervention. This measure will test for endogenous opioid mechanisms of the exercise (versus control) intervention as indexed by changes in opioid blockade effects (the difference in laboratory evoked pain response evoked between placebo and naloxone drug conditions). This is a mixed within-between subject design. Per the study protocol, the intent of outcome measures 4 and 6 was to capture opioid blockade effects (within-participant placebo-naloxone condition difference scores) at both the pre- and post-in |
Countries
United States
Participant flow
Pre-assignment details
117 subjects consented and participated in Visit 1 to evaluate the nature of chronic back pain and confirm eligibility to engage in exercise manipulation. 15 subjects were discontinued from participation following this assessment. 9 additional subjects discontinued during preintervention lab session period.
Participants by arm
| Arm | Count |
|---|---|
| Exercise Plus Placebo/Morphine/Naloxone Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes.
exercise: Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise wil | 38 |
| Placebo/Morphine/Naloxone Participants assigned to the control condition will not undergo any manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo the placebo-controlled morphine and naloxone administration intervention to assess mechanisms of exercise-related changes.
Placebo: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each)
Morphine: In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will receive: 1) 4 dose | 44 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Post Intervention /Followup | Withdrawal by Subject | 2 | 1 |
| Post Randomization/Intervention Period | Conflicting health issues | 0 | 1 |
| Post Randomization/Intervention Period | Relocated | 1 | 1 |
| Post Randomization/Intervention Period | Scheduling issues | 3 | 2 |
Baseline characteristics
| Characteristic | Total | Placebo/Morphine/Naloxone | Exercise Plus Placebo/Morphine/Naloxone |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 82 Participants | 44 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 75 Participants | 39 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 15 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 48 Participants | 25 Participants | 23 Participants |
| Region of Enrollment United States | 82 Participants | 44 Participants | 38 Participants |
| Sex: Female, Male Female | 48 Participants | 28 Participants | 20 Participants |
| Sex: Female, Male Male | 34 Participants | 16 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 44 |
| other Total, other adverse events | 0 / 38 | 0 / 44 |
| serious Total, serious adverse events | 0 / 38 | 0 / 44 |
Outcome results
Primary
Mean Change in 5-day Electronic Diary Ratings of Low Back Pain Intensity
Mean change in 5-day electronic diary ratings of low back pain intensity from pre intervention baseline to post intervention. 9 point pain scale assessing pain intensity with 0 represents no pain and 8 represents worst possible pain. Positive values indicate reduced pain post intervention.
Time frame: At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)
Population: Data was not available for analysis of 4 participants in the exercise arm and 11 participants in the control arm
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 Week Aerobic Exercise Intervention | Mean Change in 5-day Electronic Diary Ratings of Low Back Pain Intensity | Baseline (pre intervention) | 2.75 units on a scale | Standard Deviation 1.2 |
| 6 Week Aerobic Exercise Intervention | Mean Change in 5-day Electronic Diary Ratings of Low Back Pain Intensity | Change after 6 week intervention period | 0.72 units on a scale | Standard Deviation 1.18 |
| Normal Exercise (Control) | Mean Change in 5-day Electronic Diary Ratings of Low Back Pain Intensity | Baseline (pre intervention) | 2.82 units on a scale | Standard Deviation 1.38 |
| Normal Exercise (Control) | Mean Change in 5-day Electronic Diary Ratings of Low Back Pain Intensity | Change after 6 week intervention period | 0.18 units on a scale | Standard Deviation 0.91 |
Comparison: Statistical analysis applies to change after 6 week intervention periodp-value: 0.04ANCOVA
Primary
Mean of the Change in Morphine Dosage (in mg) Required to Achieve 25% Reduction in Thermal Evoked Pain Responses Relative to Baseline (Pre-intervention) Placebo Condition Responses
At a laboratory testing day pre and post intervention each participant received morphine sulphate (0.3mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02 mg/kg each with testing for thermal evoked pain response. Weight adjusted dosing was used by multiplying the weight of each patient in kg by 0.3mg (dose 1 only) or by .02mg (doses 2-4), with all doses infused in 20mL saline vehicle. Mean of the change in morphine dosage required to achieve 25 % reduction in thermal evoked pain responses on testing day at baseline (pre-intervention) and post intervention. Positive values for the change in the mean between pre and post intervention indicated decreased morphine requirements post intervention.
Time frame: At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)
Population: Data was not available for analysis of 2 participants in the exercise arm and 1 participant in the control arm
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 Week Aerobic Exercise Intervention | Mean of the Change in Morphine Dosage (in mg) Required to Achieve 25% Reduction in Thermal Evoked Pain Responses Relative to Baseline (Pre-intervention) Placebo Condition Responses | Baseline (pre intervention) | 4.17 mg | Standard Deviation 1.82 |
| 6 Week Aerobic Exercise Intervention | Mean of the Change in Morphine Dosage (in mg) Required to Achieve 25% Reduction in Thermal Evoked Pain Responses Relative to Baseline (Pre-intervention) Placebo Condition Responses | Change after 6 week intervention period | -1.62 mg | Standard Deviation 4.46 |
| Normal Exercise (Control) | Mean of the Change in Morphine Dosage (in mg) Required to Achieve 25% Reduction in Thermal Evoked Pain Responses Relative to Baseline (Pre-intervention) Placebo Condition Responses | Baseline (pre intervention) | 6.34 mg | Standard Deviation 5.63 |
| Normal Exercise (Control) | Mean of the Change in Morphine Dosage (in mg) Required to Achieve 25% Reduction in Thermal Evoked Pain Responses Relative to Baseline (Pre-intervention) Placebo Condition Responses | Change after 6 week intervention period | 0.92 mg | Standard Deviation 5.16 |
Comparison: Statistical analysis applies to change after 6 week intervention periodp-value: 0.12ANCOVA
Secondary
Mean Change in McGill Pain Questionnaire-2 Total Chronic Back Pain Ratings
Mean change in McGill Pain Questionnaire-2 total chronic back pain ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-10 where 0 represents no pain and 10 represents most intense pain. Positive values indicate decreased back pain post intervention.
Time frame: At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 Week Aerobic Exercise Intervention | Mean Change in McGill Pain Questionnaire-2 Total Chronic Back Pain Ratings | Baseline (pre intervention) | 2.66 units on a scale | Standard Deviation 1.65 |
| 6 Week Aerobic Exercise Intervention | Mean Change in McGill Pain Questionnaire-2 Total Chronic Back Pain Ratings | Change after 6 week intervention period | 1.60 units on a scale | Standard Deviation 1.58 |
| Normal Exercise (Control) | Mean Change in McGill Pain Questionnaire-2 Total Chronic Back Pain Ratings | Baseline (pre intervention) | 3.01 units on a scale | Standard Deviation 1.78 |
| Normal Exercise (Control) | Mean Change in McGill Pain Questionnaire-2 Total Chronic Back Pain Ratings | Change after 6 week intervention period | 1.36 units on a scale | Standard Deviation 1.41 |
Comparison: Statistical analysis applies to change after 6 week intervention periodp-value: 0.13ANCOVA
Secondary
Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Effect Subscale Ratings
Mean change in morphine condition Drug Effects, Liking, and Take Again (DELTA) -Drug Effect subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 1-5 where 1 represents no effect and 5 represents very strong effect. Positive values indicate decreased overall drug effects post intervention.
Time frame: At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 Week Aerobic Exercise Intervention | Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Effect Subscale Ratings | Baseline (pre intervention) | 2.72 units on a scale | Standard Deviation 0.99 |
| 6 Week Aerobic Exercise Intervention | Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Effect Subscale Ratings | Change after 6 week intervention period | 0.10 units on a scale | Standard Deviation 1.19 |
| Normal Exercise (Control) | Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Effect Subscale Ratings | Baseline (pre intervention) | 2.52 units on a scale | Standard Deviation 1 |
| Normal Exercise (Control) | Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Effect Subscale Ratings | Change after 6 week intervention period | -0.12 units on a scale | Standard Deviation 0.79 |
Comparison: Statistical analysis applies to change after 6 week intervention periodp-value: 0.61ANCOVA
Secondary
Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Liking Subscale Ratings
Mean change in morphine condition Drug Effects, Liking, and Take Again (DELTA) -Drug Liking subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-100 where 0 represents dislike a lot and 100 represents like a lot. Positive values indicate decreased drug liking post intervention.
Time frame: At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 Week Aerobic Exercise Intervention | Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Liking Subscale Ratings | Baseline (pre intervention) | 52.03 units on a scale | Standard Deviation 12.52 |
| 6 Week Aerobic Exercise Intervention | Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Liking Subscale Ratings | Change after 6 week intervention period | 4.13 units on a scale | Standard Deviation 15.5 |
| Normal Exercise (Control) | Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Liking Subscale Ratings | Baseline (pre intervention) | 52.89 units on a scale | Standard Deviation 17.57 |
| Normal Exercise (Control) | Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Liking Subscale Ratings | Change after 6 week intervention period | 1.04 units on a scale | Standard Deviation 18.68 |
Comparison: Statistical analysis applies to change after 6 week intervention periodp-value: 0.4ANCOVA
Secondary
Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Take Again Subscale Ratings
Mean change in morphine condition Drug Effects, Liking, and Take Again (DELTA) -Take Again subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-100 where 0 represents definitely would not take again and 100 represents definitely would take again. Positive values indicate decreased desire to take the drug again post intervention.
Time frame: At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 Week Aerobic Exercise Intervention | Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Take Again Subscale Ratings | Baseline (pre intervention) | 54.49 units on a scale | Standard Deviation 14.54 |
| 6 Week Aerobic Exercise Intervention | Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Take Again Subscale Ratings | Change after 6 week intervention period | 4.40 units on a scale | Standard Deviation 19.72 |
| Normal Exercise (Control) | Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Take Again Subscale Ratings | Baseline (pre intervention) | 55.04 units on a scale | Standard Deviation 22.93 |
| Normal Exercise (Control) | Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Take Again Subscale Ratings | Change after 6 week intervention period | 1.70 units on a scale | Standard Deviation 22.56 |
Comparison: Statistical analysis applies to change after 6 week intervention periodp-value: 0.57ANCOVA
Secondary
Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Euphoria Subscale Ratings
Mean change in morphine condition VAS Opioid Effects-Euphoria subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-300 where 0 means no euphoria and 300 means most euphoria possible. Positive values indicate decreased euphoria post intervention.
Time frame: At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 Week Aerobic Exercise Intervention | Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Euphoria Subscale Ratings | Baseline (pre intervention) | 100.60 units on a scale | Standard Deviation 70.35 |
| 6 Week Aerobic Exercise Intervention | Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Euphoria Subscale Ratings | Change after 6 week intervention period | 3.19 units on a scale | Standard Deviation 47.91 |
| Normal Exercise (Control) | Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Euphoria Subscale Ratings | Baseline (pre intervention) | 108.24 units on a scale | Standard Deviation 81.27 |
| Normal Exercise (Control) | Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Euphoria Subscale Ratings | Change after 6 week intervention period | 0.75 units on a scale | Standard Deviation 50.17 |
Comparison: Statistical analysis applies to change after 6 week intervention periodp-value: 0.65ANCOVA
Secondary
Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Sedation Subscale Ratings
Mean change in morphine condition VAS Opioid Effects-Sedation subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-300 where 0 means no sedation and 300 means most sedation possible. Positive values indicate decreased sedation post intervention.
Time frame: At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 Week Aerobic Exercise Intervention | Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Sedation Subscale Ratings | Baseline (pre intervention) | 66.58 units on a scale | Standard Deviation 71.54 |
| 6 Week Aerobic Exercise Intervention | Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Sedation Subscale Ratings | Change after 6 week intervention period | 12.89 units on a scale | Standard Deviation 55.3 |
| Normal Exercise (Control) | Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Sedation Subscale Ratings | Baseline (pre intervention) | 30.63 units on a scale | Standard Deviation 53.54 |
| Normal Exercise (Control) | Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Sedation Subscale Ratings | Change after 6 week intervention period | -9.95 units on a scale | Standard Deviation 38.033 |
Comparison: Statistical analysis applies to change after 6 week intervention periodp-value: 0.1ANCOVA
Secondary
Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects - Unpleasantness Subscale Ratings
Mean change in morphine condition VAS Opioid Effects - Unpleasantness subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. The score ranges from 0-300 where 0 represents no unpleasantness and 300 represents most unpleasantness possible. Positive values indicate decreased unpleasantness post intervention.
Time frame: At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 Week Aerobic Exercise Intervention | Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects - Unpleasantness Subscale Ratings | Baseline (pre intervention) | 33.58 units on a scale | Standard Deviation 36.33 |
| 6 Week Aerobic Exercise Intervention | Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects - Unpleasantness Subscale Ratings | Change after 6 week intervention period | -3.21 units on a scale | Standard Deviation 38.43 |
| Normal Exercise (Control) | Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects - Unpleasantness Subscale Ratings | Baseline (pre intervention) | 16.52 units on a scale | Standard Deviation 24.95 |
| Normal Exercise (Control) | Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects - Unpleasantness Subscale Ratings | Change after 6 week intervention period | 1.86 units on a scale | Standard Deviation 17.99 |
Comparison: Statistical analysis applies to change after 6 week intervention periodp-value: 0.046ANCOVA
Secondary
Mean Change in Placebo Condition Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form
Mean change in placebo condition ratings of acute thermal pain intensity using the McGill Pain Questionnaire-Short Form on 3 testing days at baseline (per intervention) and post intervention. The score ranges from 0-33 where 0 represents no pain and 33 represents most intense pain. Positive change values indicate decreased pain responsiveness post intervention.
Time frame: At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 Week Aerobic Exercise Intervention | Mean Change in Placebo Condition Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form | Baseline (pre intervention) | 10.23 units on a scale | Standard Deviation 9.17 |
| 6 Week Aerobic Exercise Intervention | Mean Change in Placebo Condition Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form | Change after 6 week intervention period | 0.45 units on a scale | Standard Deviation 3.99 |
| Normal Exercise (Control) | Mean Change in Placebo Condition Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form | Baseline (pre intervention) | 7.83 units on a scale | Standard Deviation 6.11 |
| Normal Exercise (Control) | Mean Change in Placebo Condition Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form | Change after 6 week intervention period | -2.14 units on a scale | Standard Deviation 4.61 |
Comparison: Statistical analysis applies to change after 6 week intervention periodp-value: 0.03ANCOVA
Secondary
Mean Change in Positive and Negative Affect Scale-Negative Affect Subscale Ratings.
Mean change in Positive and Negative Affect Scale-Negative Affect subscale ratings on 3 testing days at baseline (pre intervention) and post intervention. . Scale ratings range from 10 to 50 where 10 represents lowest negative affect possible and 50 represents highest negative affect possible. Positive values indicate decreased negative affect post intervention.
Time frame: At pre intervention baseline and again post-intervention (an expected average of 6 weeks later)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 Week Aerobic Exercise Intervention | Mean Change in Positive and Negative Affect Scale-Negative Affect Subscale Ratings. | Baseline (pre intervention) | 16.38 units on a scale | Standard Deviation 5.85 |
| 6 Week Aerobic Exercise Intervention | Mean Change in Positive and Negative Affect Scale-Negative Affect Subscale Ratings. | Change after 6 week intervention period | 0.45 units on a scale | Standard Deviation 3.99 |
| Normal Exercise (Control) | Mean Change in Positive and Negative Affect Scale-Negative Affect Subscale Ratings. | Baseline (pre intervention) | 15.43 units on a scale | Standard Deviation 4.52 |
| Normal Exercise (Control) | Mean Change in Positive and Negative Affect Scale-Negative Affect Subscale Ratings. | Change after 6 week intervention period | -2.14 units on a scale | Standard Deviation 4.61 |
Comparison: Statistical analysis applies to change after 6 week intervention periodp-value: 0.52ANCOVA
Secondary
Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for McGill Pain Questionnaire-2 Total Ratings of Back Pain.
Between-participant (aerobic exercise vs. control group) comparison of mean changes from pre- to post-intervention in opioid blockade effects for McGill Pain Questionnaire-2 Total ratings of back pain based on 3 laboratory testing days at baseline (pre intervention) and post intervention. The score ranges from 0-10 where 0 represents no pain and 10 represents most intense pain. Positive values indicate increased endogenous opioid analgesia post intervention. This measure will test the effects of the exercise (versus control) intervention on clinical outcomes as indexed by changes in opioid blockade effects (the difference in laboratory evoked pain response evoked between placebo and naloxone drug conditions). This is a mixed within-between subject design. Per the study protocol, the intent of outcome measures 4 and 6 was to capture opioid blockade effects (within-participant placebo-naloxone condition difference scores) at both the pre- and post-intervention lab assessments, an
Time frame: At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 Week Aerobic Exercise Intervention | Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for McGill Pain Questionnaire-2 Total Ratings of Back Pain. | Change after 6 week intervention period | -0.12 units on a scale | Standard Deviation 0.96 |
| 6 Week Aerobic Exercise Intervention | Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for McGill Pain Questionnaire-2 Total Ratings of Back Pain. | Baseline (pre intervention) | 0.11 units on a scale | Standard Deviation 0.82 |
| Normal Exercise (Control) | Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for McGill Pain Questionnaire-2 Total Ratings of Back Pain. | Baseline (pre intervention) | 0.18 units on a scale | Standard Deviation 0.69 |
| Normal Exercise (Control) | Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for McGill Pain Questionnaire-2 Total Ratings of Back Pain. | Change after 6 week intervention period | -0.24 units on a scale | Standard Deviation 1.28 |
Comparison: Statistical analysis applies to change after 6 week intervention periodp-value: 0.98ANCOVA
Secondary
Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form
Between-participant (aerobic exercise vs. control group) comparison of mean changes from pre- to post-intervention in opioid blockade effects for ratings of acute thermal pain intensity on the McGill Pain Questionnaire-Short Form based on 3 laboratory testing days at baseline (pre-intervention) and post intervention. The score ranges from 0-33 where 0 represents no pain and 33 represents more intense pain. Positive values indicate increased endogenous opioid analgesia post intervention. This measure will test for endogenous opioid mechanisms of the exercise (versus control) intervention as indexed by changes in opioid blockade effects (the difference in laboratory evoked pain response evoked between placebo and naloxone drug conditions). This is a mixed within-between subject design. Per the study protocol, the intent of outcome measures 4 and 6 was to capture opioid blockade effects (within-participant placebo-naloxone condition difference scores) at both the pre- and post-in
Time frame: At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6 Week Aerobic Exercise Intervention | Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form | Baseline (pre intervention) | -0.33 units on a scale | Standard Deviation 4.55 |
| 6 Week Aerobic Exercise Intervention | Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form | Change after 6 week intervention period | 1.97 units on a scale | Standard Deviation 6.32 |
| Normal Exercise (Control) | Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form | Change after 6 week intervention period | -0.61 units on a scale | Standard Deviation 5.81 |
| Normal Exercise (Control) | Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form | Baseline (pre intervention) | 0.92 units on a scale | Standard Deviation 3.81 |
Comparison: Statistical analysis applies to change after 6 week intervention periodp-value: 0.17ANCOVA