[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT06666621":3,"trial-entities:NCT06666621":182,"trial-summary:NCT06666621":186},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":21,"study_type":26,"primary_purpose":27,"phases":28,"enrollment_info":30,"interventions":33,"primary_outcomes":44,"secondary_outcomes":49,"sex":71,"minimum_age":72,"maximum_age":73,"healthy_volunteers":15,"eligibility_criteria":74,"std_ages":90,"locations":93,"central_contacts":109,"overall_officials":112,"references":116,"see_also_links":181},"NCT06666621","1792559","Endogenous Opioid Response to Injections","Antagonism of Endogenous Opioids: Use in Interpretation of Injections","RECRUITING","2026-02","2025-05","2025-05-18","2024-08-22","Middle Tennessee Research Institute","OTHER",false,"This study will study pain relief after spine injections that are used to guide care. Some improvements in pain from a procedure might be from placebo effect rather than the physiological effect of the procedure. The study will use naloxone to reverse the effect of the body's internal placebo system after a spine injection, so the placebo effect and the injection effect can be measured separately. This process may improve the understanding of spine injections and their ability to guide pain care.","Nerve blocks are commonly used in pain medicine to diagnose painful conditions and predict response to invasive procedures and surgeries. Placebo responses may cripple clinicians' ability to interpret responses to nerve blocks and guide patient care, when reported pain relief is due to placebo rather than the nerve block.\n\nExisting methods to assess placebo response in clinical practice are limited and indirect. The area that is most explored is in the diagnosis of pain from the facet joints of the spine and relies on an indirect signal from repeated diagnostic injections.\n\nLumbar medial branch radiofrequency neurotomy (LMBRN) is commonly used to treat low back pain and can lead to large improvements in pain and disability. There is a high failure rate of LMBRN even after a series of controlled prognostic injections called lumbar medial branch nerve blocks (LMBB) with local anesthetic. The discrepancy between response to LMBB and LMBRN has been attributed to the confounding of pain relief from the nerve block with pain relief from the placebo response.\n\nEndogenous opioids (EO), substances produced within the human body that bind to opioid receptors and produce opioid analgesia, are likely responsible for most of the placebo response caused by LMBB.\n\nThis study will use naloxone, an opioid receptor antagonist, to completely block the activity of EOs in patients. First, the pain relief after LMBB will be recorded - this is a combination of the effect of the nerve block and EO released in the placebo response. Normal saline will be infused, as an internal control for the state of receiving an infusion. Naloxone will then be infused, reversing EO-dependent placebo analgesia - the analgesia remaining will be from the nerve block. Finally, clinical outcomes from LMBRN will be collected to determine whether using naloxone with LMBB can improve prediction of outcomes with LMBRN.\n\nNaloxone will be used to probe a mechanism of procedurally-induced endogenous-opioid mediated placebo analgesia. No IND is pursued in this study.\n\nThese data will provide detailed parameters of placebo response from LMBB, improving interpretation of LMBB for estimation of prevalence of zygapophyseal joint pain and for prognostication of LMBRN.\n\nFurthermore, if this methodology of EO reversible analgesia is feasible for investigation of placebo from LMBB, it will be more broadly investigated in diagnostic and prognostic injections used in interventional pain management.",[19,20],"Low Back Pain","Zygapophyseal Joint Arthritis",[22,23,24,25],"low back pain","zygapophysial joint arthritis","endogenous opioids","lumbar medial branch block","INTERVENTIONAL","DIAGNOSTIC",[29],"PHASE4",{"count":31,"type":32},33,"ESTIMATED",[34,40],{"type":35,"name":36,"description":37,"armGroupLabels":38},"DRUG","Normal saline infusion","After assessment of response to lumbar medial branch block, 8 ml normal saline will be infused through IV over several minutes. 10 minutes will pass, and response to lumbar medial branch block procedure will be re-assessed.\n\nAfter this step, naloxone infusion will occur (see next intervention)",[39],"Single arm study: endogenous opioid blockade",{"type":35,"name":41,"description":42,"armGroupLabels":43},"Naloxone infusion","After infusion of normal saline and re-assessment of response to lumbar medial branch block procedure, 8 milligrams of naloxone will be infused over several minutes. Then after 10 minutes, response to lumbar medial branch block procedure will be re-reassessed for the final time.",[39],[45],{"measure":46,"description":47,"timeFrame":48},"Endogenous opioid-dependent placebo analgesia","Endogenous opioid-dependent placebo analgesia is defined as change in analgesia after lumbar medial branch block #1 (measured by numeric pain rating scale) after infusing naloxone","10 minutes after naloxone infusion",[50,54,58,62,65,68],{"measure":51,"description":52,"timeFrame":53},"Saline-reversible analgesia","Saline-reversible analgesia is defined as change in analgesia after lumbar medial branch block #1 (measured by numeric pain rating scale) after infusing saline","10 minutes after saline infusion",{"measure":55,"description":56,"timeFrame":57},"Change in low back pain score after Lumbar Medial Branch Block #2","Change in Numeric Pain Rating Scale score for low back pain after Lumbar Medial Branch Block #2","Approximately 2 weeks after Lumbar Medial Branch Block #1, and before Lumbar Medial Branch Radiofrequency Neurotomy",{"measure":59,"description":60,"timeFrame":61},"Change in low back pain score after Lumbar Medial Branch Radiofrequency Neurotomy","Change in Numeric Pain Rating Scale score for low back pain after Lumbar Medial Branch Neurotomy","Baseline, then 6 weeks, 3 months, 6 months after Lumbar Medial Branch Radiofrequency Neurotomy",{"measure":63,"description":64,"timeFrame":61},"Change in McGill Pain Questionnaire-2 after Lumbar Medial Branch Radiofrequency Neurotomy","Change in McGill Pain Questionnaire-2 score after Lumbar Medial Branch Radiofrequency Neurotomy",{"measure":66,"description":67,"timeFrame":61},"Change in MQS-III after Lumbar Medial Branch Radiofrequency Neurotomy","Change in MQS-III score after Lumbar Medial Branch Radiofrequency Neurotomy",{"measure":69,"description":70,"timeFrame":61},"Change in Patient-Reported Outcomes Measurement Information System-29 after Lumbar Medial Branch Radiofrequency Neurotomy","Change in Patient-Reported Outcomes Measurement Information System-29 score after Lumbar Medial Branch Radiofrequency Neurotomy","ALL","18 Years",null,{"inclusion":75,"exclusion":79,"raw_text":89},[76,77,78],"Capable of understanding and providing consent in English and capable of complying with the outcome instruments used","≥3 months low back pain with persistent limiting symptoms despite conventional treatment (physical therapy and oral medications)","Low back pain NRS ≥ 4\u002F10 in intensity on 7-day average and at time of lumbar medial branch block",[80,81,82,83,84,85,86,87,88],"Daily use of opioid medications or recreational drugs, or if using opioids PRN, report of opioid use within the 3 days prior to participating in the protocol","Positive urine drug screen for opioid medication on the day of naloxone administration","Allergy to naloxone","Refusal of or failure to place IV","Previous LMBB or LMBRN","Known spine condition that may affect the ability to diagnose or treat facet pain or lead to spine surgery (e.g. instability, severe spinal stenosis, radiculopathy, previous spine operation resulting in alteration of anatomy targeted by LMBB or LMBRFN)","Active medical condition that would limit the safety of naloxone administration (e.g. severe kidney or liver failure, unstable cardiac disease, infection, severe coagulopathy)","Psychiatric, medical, neurologic, or pain-related disorder that may compromise the ability of the patient to accurately report changes in low back pain","Requirement for procedural sedation to tolerate LMBB","Inclusion Criteria:\n\n* Capable of understanding and providing consent in English and capable of complying with the outcome instruments used\n* ≥3 months low back pain with persistent limiting symptoms despite conventional treatment (physical therapy and oral medications)\n* Low back pain NRS ≥ 4\u002F10 in intensity on 7-day average and at time of lumbar medial branch block\n\nExclusion Criteria:\n\n* Daily use of opioid medications or recreational drugs, or if using opioids PRN, report of opioid use within the 3 days prior to participating in the protocol\n* Positive urine drug screen for opioid medication on the day of naloxone administration\n* Allergy to naloxone\n* Refusal of or failure to place IV\n* Previous LMBB or LMBRN\n* Known spine condition that may affect the ability to diagnose or treat facet pain or lead to spine surgery (e.g. instability, severe spinal stenosis, radiculopathy, previous spine operation resulting in alteration of anatomy targeted by LMBB or LMBRFN)\n* Active medical condition that would limit the safety of naloxone administration (e.g. severe kidney or liver failure, unstable cardiac disease, infection, severe coagulopathy)\n* Psychiatric, medical, neurologic, or pain-related disorder that may compromise the ability of the patient to accurately report changes in low back pain\n* Requirement for procedural sedation to tolerate LMBB",[91,92],"ADULT","OLDER_ADULT",[94],{"facility":95,"status":8,"city":96,"state":97,"zip":98,"country":99,"contacts":100,"geoPoint":106},"VA Tennessee Valley Healthcare System","Nashville","Tennessee","37212","United States",[101],{"name":102,"role":103,"phone":104,"email":105},"William E Rivers, DO","CONTACT","615-225-6559","william.rivers@va.gov",{"lat":107,"lon":108},36.16589,-86.78444,[110],{"name":102,"role":103,"phone":111,"email":105},"859-513-9793",[113],{"name":102,"affiliation":114,"role":115},"Tennessee Valley Healthcare System VA","PRINCIPAL_INVESTIGATOR",[117,121,124,127,130,133,136,139,142,145,148,151,154,157,160,163,166,169,172,175,178],{"pmid":118,"type":119,"citation":120},"8783319","BACKGROUND","Benedetti F. The opposite effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia. Pain. 1996 Mar;64(3):535-543. doi: 10.1016\u002F0304-3959(95)00179-4.",{"pmid":122,"type":119,"citation":123},"20613471","Cohen SP, Williams KA, Kurihara C, Nguyen C, Shields C, Kim P, Griffith SR, Larkin TM, Crooks M, Williams N, Morlando B, Strassels SA. Multicenter, randomized, comparative cost-effectiveness study comparing 0, 1, and 2 diagnostic medial branch (facet joint nerve) block treatment paradigms before lumbar facet radiofrequency denervation. Anesthesiology. 2010 Aug;113(2):395-405. doi: 10.1097\u002FALN.0b013e3181e33ae5.",{"pmid":125,"type":119,"citation":126},"17662665","Cohen SP, Stojanovic MP, Crooks M, Kim P, Schmidt RK, Shields CH, Croll S, Hurley RW. Lumbar zygapophysial (facet) joint radiofrequency denervation success as a function of pain relief during diagnostic medial branch blocks: a multicenter analysis. Spine J. 2008 May-Jun;8(3):498-504. doi: 10.1016\u002Fj.spinee.2007.04.022. Epub 2007 Jun 18.",{"pmid":128,"type":119,"citation":129},"17912133","Manchukonda R, Manchikanti KN, Cash KA, Pampati V, Manchikanti L. Facet joint pain in chronic spinal pain: an evaluation of prevalence and false-positive rate of diagnostic blocks. J Spinal Disord Tech. 2007 Oct;20(7):539-45. doi: 10.1097\u002FBSD.0b013e3180577812.",{"pmid":131,"type":119,"citation":132},"29847426","Cohen SP, Doshi TL, Constantinescu OC, Zhao Z, Kurihara C, Larkin TM, Griffith SR, Jacobs MB, Kroski WJ, Dawson TC, Fowler IM, White RL, Verdun AJ, Jamison DE, Anderson-White M, Shank SE, Pasquina PF. Effectiveness of Lumbar Facet Joint Blocks and Predictive Value before Radiofrequency Denervation: The Facet Treatment Study (FACTS), a Randomized, Controlled Clinical Trial. Anesthesiology. 2018 Sep;129(3):517-535. doi: 10.1097\u002FALN.0000000000002274.",{"pmid":134,"type":119,"citation":135},"26218947","Boswell MV, Manchikanti L, Kaye AD, Bakshi S, Gharibo CG, Gupta S, Jha SS, Nampiaparampil DE, Simopoulos TT, Hirsch JA. A Best-Evidence Systematic Appraisal of the Diagnostic Accuracy and Utility of Facet (Zygapophysial) Joint Injections in Chronic Spinal Pain. Pain Physician. 2015 Jul-Aug;18(4):E497-533.",{"pmid":137,"type":119,"citation":138},"10942860","Kaptchuk TJ, Goldman P, Stone DA, Stason WB. Do medical devices have enhanced placebo effects? J Clin Epidemiol. 2000 Aug;53(8):786-92. doi: 10.1016\u002Fs0895-4356(00)00206-7.",{"pmid":140,"type":119,"citation":141},"31583358","Finniss D, Nicholas M, Brooker C, Cousins M, Benedetti F. Magnitude, response, and psychological determinants of placebo effects in chronic low-back pain: a randomised, double-blinded, controlled trial. Pain Rep. 2019 Jun 7;4(3):e744. doi: 10.1097\u002FPR9.0000000000000744. eCollection 2019 May-Jun.",{"pmid":143,"type":119,"citation":144},"16120776","Zubieta JK, Bueller JA, Jackson LR, Scott DJ, Xu Y, Koeppe RA, Nichols TE, Stohler CS. Placebo effects mediated by endogenous opioid activity on mu-opioid receptors. J Neurosci. 2005 Aug 24;25(34):7754-62. doi: 10.1523\u002FJNEUROSCI.0439-05.2005.",{"pmid":146,"type":119,"citation":147},"32422213","Bagley EE, Ingram SL. Endogenous opioid peptides in the descending pain modulatory circuit. Neuropharmacology. 2020 Aug 15;173:108131. doi: 10.1016\u002Fj.neuropharm.2020.108131. Epub 2020 May 15.",{"pmid":149,"type":119,"citation":150},"18923027","Petrovic P, Pleger B, Seymour B, Kloppel S, De Martino B, Critchley H, Dolan RJ. Blocking central opiate function modulates hedonic impact and anterior cingulate response to rewards and losses. J Neurosci. 2008 Oct 15;28(42):10509-16. doi: 10.1523\u002FJNEUROSCI.2807-08.2008.",{"pmid":152,"type":119,"citation":153},"32563287","Colloca L. Placebo effects in pain. Int Rev Neurobiol. 2020;153:167-185. doi: 10.1016\u002Fbs.irn.2020.04.001. Epub 2020 Jun 9.",{"pmid":155,"type":119,"citation":156},"30562268","Bruehl S, Burns JW, Morgan A, Koltyn K, Gupta R, Buvanendran A, Edwards D, Chont M, Kingsley PJ, Marnett L, Stone A, Patel S. The association between endogenous opioid function and morphine responsiveness: a moderating role for endocannabinoids. Pain. 2019 Mar;160(3):676-687. doi: 10.1097\u002Fj.pain.0000000000001447.",{"pmid":158,"type":119,"citation":159},"32569082","Bruehl S, Burns JW, Koltyn K, Gupta R, Buvanendran A, Edwards D, Chont M, Wu YH, Qu'd D, Stone A. Are endogenous opioid mechanisms involved in the effects of aerobic exercise training on chronic low back pain? A randomized controlled trial. Pain. 2020 Dec;161(12):2887-2897. doi: 10.1097\u002Fj.pain.0000000000001969.",{"pmid":161,"type":119,"citation":162},"17578917","Wager TD, Scott DJ, Zubieta JK. Placebo effects on human mu-opioid activity during pain. Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11056-61. doi: 10.1073\u002Fpnas.0702413104. Epub 2007 Jun 19.",{"pmid":164,"type":119,"citation":165},"28701195","Wartolowska KA, Gerry S, Feakins BG, Collins GS, Cook J, Judge A, Carr AJ. A meta-analysis of temporal changes of response in the placebo arm of surgical randomized controlled trials: an update. Trials. 2017 Jul 12;18(1):323. doi: 10.1186\u002Fs13063-017-2070-9.",{"pmid":167,"type":119,"citation":168},"9762741","Kaplan M, Dreyfuss P, Halbrook B, Bogduk N. The ability of lumbar medial branch blocks to anesthetize the zygapophysial joint. A physiologic challenge. Spine (Phila Pa 1976). 1998 Sep 1;23(17):1847-52. doi: 10.1097\u002F00007632-199809010-00008.",{"pmid":170,"type":119,"citation":171},"10806505","Dreyfuss P, Halbrook B, Pauza K, Joshi A, McLarty J, Bogduk N. Efficacy and validity of radiofrequency neurotomy for chronic lumbar zygapophysial joint pain. Spine (Phila Pa 1976). 2000 May 15;25(10):1270-7. doi: 10.1097\u002F00007632-200005150-00012.",{"pmid":173,"type":119,"citation":174},"9127924","Dreyfuss P, Schwarzer AC, Lau P, Bogduk N. Specificity of lumbar medial branch and L5 dorsal ramus blocks. A computed tomography study. Spine (Phila Pa 1976). 1997 Apr 15;22(8):895-902. doi: 10.1097\u002F00007632-199704150-00013.",{"pmid":176,"type":119,"citation":177},"26005713","McCormick ZL, Marshall B, Walker J, McCarthy R, Walega DR. Long-Term Function, Pain and Medication Use Outcomes of Radiofrequency Ablation for Lumbar Facet Syndrome. Int J Anesth Anesth. 2015;2(2):028. doi: 10.23937\u002F2377-4630\u002F2\u002F2\u002F1028.",{"pmid":179,"type":119,"citation":180},"23279154","MacVicar J, Borowczyk JM, MacVicar AM, Loughnan BM, Bogduk N. Lumbar medial branch radiofrequency neurotomy in New Zealand. Pain Med. 2013 May;14(5):639-45. doi: 10.1111\u002Fpme.12000. Epub 2012 Dec 28.",[],{"nct_id":4,"conditions":183,"biomarkers":185},[184,20],"Lower Back Pain",[],{"nct_id":4,"found":187,"summary":188,"prompt_version":198},true,{"design":189,"status":190,"heading":191,"summary":192,"follow_up":193,"word_count":194,"commitments":195,"compensation":196,"drugs_mentioned":197},"This interventional study plans to enroll 33 participants. It will involve giving participants specific treatments (normal saline and naloxone infusions) and then observing their response.","completed","Understanding Pain Relief from Spine Injections for Low Back Pain","This study is looking at how different types of pain relief work after spine injections for low back pain. It aims to understand if some pain relief comes from a 'placebo effect' (your body's natural pain relief system) rather than just the injection itself. You might be able to join if you are 18 or older, have had low back pain for at least three months that hasn't improved with usual treatments, and your pain is rated 4 out of 10 or higher. Participants will receive an intravenous (IV) infusion of normal saline, followed by an IV infusion of naloxone. Naloxone is a medication that can block your body's natural pain relief system. The main goal is to measure how much pain relief is due to your body's natural system after the naloxone infusion. The study status is currently unclear.","Your pain response will be measured at 10 minutes after the naloxone infusion.",140,"You will receive an infusion of normal saline, followed by a re-assessment of your pain. Then, you will receive an infusion of naloxone, followed by a final pain re-assessment.","Not stated in the trial record.",[41],"v2"]