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| ID | Type | Description | Link |
|---|---|---|---|
| R01DA037891 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 6 week aerobic exercise intervention | Experimental | 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) | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 6 week aerobic exercise intervention | Behavioral | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later) |
| 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. | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stephen Bruehl, PhD | Vanderbilt University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rush University | Chicago | Illinois | 60612 | United States | ||
| Vanderbilt University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16181935 | Background | Bement MK, Sluka KA. Low-intensity exercise reverses chronic muscle pain in the rat in a naloxone-dependent manner. Arch Phys Med Rehabil. 2005 Sep;86(9):1736-40. doi: 10.1016/j.apmr.2005.03.029. | |
| 23748117 | Background | Bruehl S, Burns JW, Gupta R, Buvanendran A, Chont M, Kinner E, Schuster E, Passik S, France CR. Endogenous opioid function mediates the association between laboratory-evoked pain sensitivity and morphine analgesic responses. Pain. 2013 Sep;154(9):1856-1864. doi: 10.1016/j.pain.2013.06.002. Epub 2013 Jun 6. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
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| Pre Randomization - Pre Intervention |
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| Post Intervention /Followup |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Data was not available for analysis of 2 participants in the exercise arm and 1 participant in the control arm | Posted | Mean | Standard Deviation | mg | At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later) |
Adverse event data was collected from consent to the completion of the last study visit.(approximately 12 weeks).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Stephen Bruehl, Ph.D. | Vanderbilt University Medical Center | 615-936-1821 | stephen.bruehl@vumc.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Nov 6, 2018 | Oct 23, 2019 | ICF_000.pdf |
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 16, 2015 | May 20, 2020 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D059350 | Chronic Pain |
| ID | Term |
|---|---|
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D009020 | Morphine |
| D009270 | Naloxone |
| ID | Term |
|---|---|
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
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| Placebo | Drug | 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). |
|
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| Morphine | Drug | 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). |
|
|
| naloxone | Drug | 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). |
|
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| At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later) |
| 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 | 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 | 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. | At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later) |
| 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 | At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later) |
| 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. | At pre intervention baseline and again post-intervention (an expected average of 6 weeks later) |
| 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. | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) |
| 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. | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) |
| 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. | 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 | 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. | 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 | 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. | 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 | 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. | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) |
| Nashville |
| Tennessee |
| 37212 |
| United States |
| 24553304 | Background | Bruehl S, Burns JW, Gupta R, Buvanendran A, Chont M, Schuster E, France CR. Endogenous opioid inhibition of chronic low-back pain influences degree of back pain relief after morphine administration. Reg Anesth Pain Med. 2014 Mar-Apr;39(2):120-5. doi: 10.1097/AAP.0000000000000058. |
| 14659514 | Background | Bruehl S, Chung OY, Burns JW, Biridepalli S. The association between anger expression and chronic pain intensity: evidence for partial mediation by endogenous opioid dysfunction. Pain. 2003 Dec;106(3):317-324. doi: 10.1016/S0304-3959(03)00319-1. |
| 17284546 | Background | Chatzitheodorou D, Kabitsis C, Malliou P, Mougios V. A pilot study of the effects of high-intensity aerobic exercise versus passive interventions on pain, disability, psychological strain, and serum cortisol concentrations in people with chronic low back pain. Phys Ther. 2007 Mar;87(3):304-12. doi: 10.2522/ptj.20060080. Epub 2007 Feb 6. |
| 3246253 | Background | Droste C, Meyer-Blankenburg H, Greenlee MW, Roskamm H. Effect of physical exercise on pain thresholds and plasma beta-endorphins in patients with silent and symptomatic myocardial ischaemia. Eur Heart J. 1988 Dec;9 Suppl N:25-33. doi: 10.1093/eurheartj/9.suppl_n.25. |
| 1654741 | Background | Eriksson SV, Lundeberg T, Lundeberg S. Interaction of diazepam and naloxone on acupuncture induced pain relief. Am J Chin Med. 1991;19(1):1-7. doi: 10.1142/S0192415X91000028. |
| 2883837 | Background | Ernst M, Lee MH. Influence of naloxone on electro-acupuncture analgesia using an experimental dental pain test. Review of possible mechanisms of action. Acupunct Electrother Res. 1987;12(1):5-22. doi: 10.3727/036012987816358940. |
| 17444920 | Background | Fritz MS, Mackinnon DP. Required sample size to detect the mediated effect. Psychol Sci. 2007 Mar;18(3):233-9. doi: 10.1111/j.1467-9280.2007.01882.x. |
| 6945616 | Background | Haier RJ, Quaid K, Mills JC. Naloxone alters pain perception after jogging. Psychiatry Res. 1981 Oct;5(2):231-2. doi: 10.1016/0165-1781(81)90052-4. No abstract available. |
| 15944883 | Background | Hoffman MD, Shepanski MA, Mackenzie SP, Clifford PS. Experimentally induced pain perception is acutely reduced by aerobic exercise in people with chronic low back pain. J Rehabil Res Dev. 2005 Mar-Apr;42(2):183-90. doi: 10.1682/jrrd.2004.06.0065. |
| 19679181 | Background | Hutchinson MR, Zhang Y, Shridhar M, Evans JH, Buchanan MM, Zhao TX, Slivka PF, Coats BD, Rezvani N, Wieseler J, Hughes TS, Landgraf KE, Chan S, Fong S, Phipps S, Falke JJ, Leinwand LA, Maier SF, Yin H, Rice KC, Watkins LR. Evidence that opioids may have toll-like receptor 4 and MD-2 effects. Brain Behav Immun. 2010 Jan;24(1):83-95. doi: 10.1016/j.bbi.2009.08.004. Epub 2009 Aug 11. |
| 6330643 | Background | Janal MN, Colt EWD, Clark CW, Glusman M. Pain sensitivity, mood and plasma endocrine levels in man following long-distance running: effects of naloxone. Pain. 1984 May;19(1):13-25. doi: 10.1016/0304-3959(84)90061-7. |
| 22534819 | Background | King CD, Goodin B, Kindler LL, Caudle RM, Edwards RR, Gravenstein N, Riley JL 3rd, Fillingim RB. Reduction of conditioned pain modulation in humans by naltrexone: an exploratory study of the effects of pain catastrophizing. J Behav Med. 2013 Jun;36(3):315-27. doi: 10.1007/s10865-012-9424-2. Epub 2012 Apr 26. |
| 10701712 | Background | Koltyn KF. Analgesia following exercise: a review. Sports Med. 2000 Feb;29(2):85-98. doi: 10.2165/00007256-200029020-00002. |
| 20878051 | Background | Meeus M, Roussel NA, Truijen S, Nijs J. Reduced pressure pain thresholds in response to exercise in chronic fatigue syndrome but not in chronic low back pain: an experimental study. J Rehabil Med. 2010 Oct;42(9):884-90. doi: 10.2340/16501977-0595. |
| 3486546 | Background | Olausson B, Eriksson E, Ellmarker L, Rydenhag B, Shyu BC, Andersson SA. Effects of naloxone on dental pain threshold following muscle exercise and low frequency transcutaneous nerve stimulation: a comparative study in man. Acta Physiol Scand. 1986 Feb;126(2):299-305. doi: 10.1111/j.1748-1716.1986.tb07818.x. |
| 2542682 | Background | Paulev PE, Thorboll JE, Nielsen U, Kruse P, Jordal R, Bach FW, Fenger M, Pokorski M. Opioid involvement in the perception of pain due to endurance exercise in trained man. Jpn J Physiol. 1989;39(1):67-74. doi: 10.2170/jjphysiol.39.67. |
| 15641418 | Background | Preacher KJ, Hayes AF. SPSS and SAS procedures for estimating indirect effects in simple mediation models. Behav Res Methods Instrum Comput. 2004 Nov;36(4):717-31. doi: 10.3758/bf03206553. |
| 18697684 | Background | Preacher KJ, Hayes AF. Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav Res Methods. 2008 Aug;40(3):879-91. doi: 10.3758/brm.40.3.879. |
| 1009225 | Background | Prentice RL. A generalization of the probit and logit methods for dose response curves. Biometrics. 1976 Dec;32(4):761-8. |
| 15016395 | Background | Rainville J, Hartigan C, Jouve C, Martinez E. The influence of intense exercise-based physical therapy program on back pain anticipated before and induced by physical activities. Spine J. 2004 Mar-Apr;4(2):176-83. doi: 10.1016/j.spinee.2003.08.031. |
| 22704853 | Background | Scheef L, Jankowski J, Daamen M, Weyer G, Klingenberg M, Renner J, Mueckter S, Schurmann B, Musshoff F, Wagner M, Schild HH, Zimmer A, Boecker H. An fMRI study on the acute effects of exercise on pain processing in trained athletes. Pain. 2012 Aug;153(8):1702-1714. doi: 10.1016/j.pain.2012.05.008. Epub 2012 Jun 16. |
| 22850802 | Background | Shnayderman I, Katz-Leurer M. An aerobic walking programme versus muscle strengthening programme for chronic low back pain: a randomized controlled trial. Clin Rehabil. 2013 Mar;27(3):207-14. doi: 10.1177/0269215512453353. Epub 2012 Jul 31. |
| 21386701 | Background | Stagg NJ, Mata HP, Ibrahim MM, Henriksen EJ, Porreca F, Vanderah TW, Philip Malan T Jr. Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model: role of endogenous opioids. Anesthesiology. 2011 Apr;114(4):940-8. doi: 10.1097/ALN.0b013e318210f880. |
| 18522936 | Background | Sun Y, Gan TJ, Dubose JW, Habib AS. Acupuncture and related techniques for postoperative pain: a systematic review of randomized controlled trials. Br J Anaesth. 2008 Aug;101(2):151-60. doi: 10.1093/bja/aen146. Epub 2008 Jun 2. |
| 9646895 | Background | Ulett GA, Han S, Han JS. Electroacupuncture: mechanisms and clinical application. Biol Psychiatry. 1998 Jul 15;44(2):129-38. doi: 10.1016/s0006-3223(97)00394-6. |
| 2168836 | Background | Willer JC, Le Bars D, De Broucker T. Diffuse noxious inhibitory controls in man: involvement of an opioidergic link. Eur J Pharmacol. 1990 Jul 3;182(2):347-55. doi: 10.1016/0014-2999(90)90293-f. |
| 30640659 | Derived | Bruehl S, Stone AL, Palmer C, Edwards DA, Buvanendran A, Gupta R, Chont M, Kennedy M, Burns JW. Self-reported cumulative medical opioid exposure and subjective responses on first use of opioids predict analgesic and subjective responses to placebo-controlled opioid administration. Reg Anesth Pain Med. 2019 Jan;44(1):92-99. doi: 10.1136/rapm-2018-000008. |
| NOT COMPLETED |
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| Post Intervention Morphine |
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| Post Intervention Naloxone |
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| COMPLETED |
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| NOT COMPLETED |
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| BG001 | 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 |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| OG000 | 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 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 |
| OG001 | Normal Exercise (Control) | 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 |
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| 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. | Data was not available for analysis of 4 participants in the exercise arm and 11 participants in the control arm | Posted | Mean | Standard Deviation | units on a scale | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) |
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| 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. | Posted | Mean | Standard Deviation | units on a scale | At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later) |
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| 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 | Posted | Mean | Standard Deviation | units on a scale | At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later) |
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| 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. | Posted | Mean | Standard Deviation | units on a scale | At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later) |
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| 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 | Posted | Mean | Standard Deviation | units on a scale | At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later) |
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| 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. | Posted | Mean | Standard Deviation | units on a scale | At pre intervention baseline and again post-intervention (an expected average of 6 weeks later) |
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| 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. | Posted | Mean | Standard Deviation | units on a scale | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) |
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| 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. | Posted | Mean | Standard Deviation | units on a scale | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) |
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| 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. | Posted | Mean | Standard Deviation | units on a scale | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) |
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| 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. | Posted | Mean | Standard Deviation | units on a scale | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) |
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| 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. | Posted | Mean | Standard Deviation | units on a scale | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) |
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| 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. | Posted | Mean | Standard Deviation | units on a scale | At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later) |
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| EG001 | 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 | 0 | 44 | 0 | 44 | 0 | 44 |
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| D006571 |
| Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |