Trial Outcomes & Findings for Reduced Opioid Analgesic Requirements Via Improved Endogenous Opioid Function (NCT NCT02469077)
NCT ID: NCT02469077
Last Updated: 2020-09-23
Results Overview
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.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
117 participants
Primary outcome timeframe
At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)
Results posted on
2020-09-23
Participant Flow
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.
Participant milestones
| Measure |
6 Week Aerobic Exercise Intervention
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 laboratory evoked thermal pain response testing with placebo-controlled morphine and naloxone administration to assess mechanisms of exercise-related changes.
|
Normal Exercise (Control)
Participants assigned to the control condition will not undergo any exercise 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 laboratory evoked thermal pain response testing with placebo-controlled morphine and naloxone administration to assess mechanisms of exercise-related changes.
|
|---|---|---|
|
Pre Randomization - Pre Intervention
STARTED
|
44
|
49
|
|
Pre Randomization - Pre Intervention
Pre Intervention Placebo
|
44
|
49
|
|
Pre Randomization - Pre Intervention
Pre Intervention Morpine
|
44
|
49
|
|
Pre Randomization - Pre Intervention
Pre Intervention Naloxone
|
44
|
49
|
|
Pre Randomization - Pre Intervention
COMPLETED
|
44
|
49
|
|
Pre Randomization - Pre Intervention
NOT COMPLETED
|
0
|
0
|
|
Post Randomization/Intervention Period
STARTED
|
44
|
49
|
|
Post Randomization/Intervention Period
COMPLETED
|
40
|
45
|
|
Post Randomization/Intervention Period
NOT COMPLETED
|
4
|
4
|
|
Post Intervention /Followup
STARTED
|
40
|
45
|
|
Post Intervention /Followup
Post Intervention Placebo
|
39
|
45
|
|
Post Intervention /Followup
Post Intervention Morphine
|
40
|
45
|
|
Post Intervention /Followup
Post Intervention Naloxone
|
39
|
44
|
|
Post Intervention /Followup
COMPLETED
|
38
|
44
|
|
Post Intervention /Followup
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
6 Week Aerobic Exercise Intervention
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 laboratory evoked thermal pain response testing with placebo-controlled morphine and naloxone administration to assess mechanisms of exercise-related changes.
|
Normal Exercise (Control)
Participants assigned to the control condition will not undergo any exercise 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 laboratory evoked thermal pain response testing with placebo-controlled morphine and naloxone administration to assess mechanisms of exercise-related changes.
|
|---|---|---|
|
Post Randomization/Intervention Period
Scheduling issues
|
3
|
2
|
|
Post Randomization/Intervention Period
Relocated
|
1
|
1
|
|
Post Randomization/Intervention Period
Conflicting health issues
|
0
|
1
|
|
Post Intervention /Followup
Withdrawal by Subject
|
2
|
1
|
Baseline Characteristics
Reduced Opioid Analgesic Requirements Via Improved Endogenous Opioid Function
Baseline characteristics by cohort
| Measure |
Exercise Plus Placebo/Morphine/Naloxone
n=38 Participants
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
|
Placebo/Morphine/Naloxone
n=44 Participants
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
|
Total
n=82 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
38 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
82 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
36 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
10 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
38 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
82 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
6 Week Aerobic Exercise Intervention
n=36 Participants
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
|
Normal Exercise (Control)
n=43 Participants
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
|
|---|---|---|
|
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
|
6.34 mg
Standard Deviation 5.63
|
|
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
|
0.92 mg
Standard Deviation 5.16
|
PRIMARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
6 Week Aerobic Exercise Intervention
n=34 Participants
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
|
Normal Exercise (Control)
n=33 Participants
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
|
|---|---|---|
|
Mean Change in 5-day Electronic Diary Ratings of Low Back Pain Intensity
Baseline (pre intervention)
|
2.75 units on a scale
Standard Deviation 1.20
|
2.82 units on a scale
Standard Deviation 1.38
|
|
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
|
0.18 units on a scale
Standard Deviation 0.91
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
6 Week Aerobic Exercise Intervention
n=38 Participants
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
|
Normal Exercise (Control)
n=44 Participants
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
|
|---|---|---|
|
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
|
7.83 units on a scale
Standard Deviation 6.11
|
|
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
|
-2.14 units on a scale
Standard Deviation 4.61
|
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
6 Week Aerobic Exercise Intervention
n=38 Participants
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
|
Normal Exercise (Control)
n=44 Participants
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
|
|---|---|---|
|
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
|
0.92 units on a scale
Standard Deviation 3.81
|
|
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
|
-0.61 units on a scale
Standard Deviation 5.81
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
6 Week Aerobic Exercise Intervention
n=38 Participants
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
|
Normal Exercise (Control)
n=44 Participants
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
|
|---|---|---|
|
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
|
3.01 units on a scale
Standard Deviation 1.78
|
|
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
|
1.36 units on a scale
Standard Deviation 1.41
|
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
6 Week Aerobic Exercise Intervention
n=38 Participants
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
|
Normal Exercise (Control)
n=44 Participants
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
|
|---|---|---|
|
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
|
0.18 units on a scale
Standard Deviation 0.69
|
|
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
|
-0.24 units on a scale
Standard Deviation 1.28
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
6 Week Aerobic Exercise Intervention
n=38 Participants
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
|
Normal Exercise (Control)
n=44 Participants
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
|
|---|---|---|
|
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
|
15.43 units on a scale
Standard Deviation 4.52
|
|
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
|
-2.14 units on a scale
Standard Deviation 4.61
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
6 Week Aerobic Exercise Intervention
n=38 Participants
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
|
Normal Exercise (Control)
n=44 Participants
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
|
|---|---|---|
|
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
|
108.24 units on a scale
Standard Deviation 81.27
|
|
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
|
0.75 units on a scale
Standard Deviation 50.17
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
6 Week Aerobic Exercise Intervention
n=38 Participants
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
|
Normal Exercise (Control)
n=44 Participants
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
|
|---|---|---|
|
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
|
30.63 units on a scale
Standard Deviation 53.54
|
|
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 55.30
|
-9.95 units on a scale
Standard Deviation 38.033
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
6 Week Aerobic Exercise Intervention
n=38 Participants
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
|
Normal Exercise (Control)
n=44 Participants
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
|
|---|---|---|
|
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
|
16.52 units on a scale
Standard Deviation 24.95
|
|
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
|
1.86 units on a scale
Standard Deviation 17.99
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
6 Week Aerobic Exercise Intervention
n=38 Participants
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
|
Normal Exercise (Control)
n=44 Participants
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
|
|---|---|---|
|
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
|
2.52 units on a scale
Standard Deviation 1.00
|
|
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
|
-0.12 units on a scale
Standard Deviation 0.79
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
6 Week Aerobic Exercise Intervention
n=38 Participants
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
|
Normal Exercise (Control)
n=44 Participants
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
|
|---|---|---|
|
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
|
52.89 units on a scale
Standard Deviation 17.57
|
|
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 15.50
|
1.04 units on a scale
Standard Deviation 18.68
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
6 Week Aerobic Exercise Intervention
n=38 Participants
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
|
Normal Exercise (Control)
n=44 Participants
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
|
|---|---|---|
|
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
|
55.04 units on a scale
Standard Deviation 22.93
|
|
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
|
1.70 units on a scale
Standard Deviation 22.56
|
Adverse Events
Exercise Plus Placebo/Morphine/Naloxone
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo/Morphine/Naloxone
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Stephen Bruehl, Ph.D.
Vanderbilt University Medical Center
Phone: 615-936-1821
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place