Conditioned Open-label Placebo (COLP) for Peri-operative Pain Management in Patients With Head and Neck Cancer
NCT ID: NCT04973748
Last Updated: 2024-08-23
Study Results
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Basic Information
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COMPLETED
NA
9 participants
INTERVENTIONAL
2023-02-07
2024-06-28
Brief Summary
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Detailed Description
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The opioid epidemic is a considerable problem in the United States, with more than 5 million Americans currently affected by opioid-related substance use disorders. While prescription medications may be thought of as safe and controlled, many opioid-naïve patients report continuing to take prescription opioids for over one year after surgery, and the majority of heroin users report starting with abuse of prescription opioids. At the same time, prescription opioids have more than doubled from 2001-2013 and multiple studies in other surgical specialties suggest that patients receive opioids in excess of the patient's peri-operative pain needs Prior efforts to battle this epidemic have included the increased use of multimodal analgesia, policies to limit the amount of opioids able to be prescribed at one time, and databases to track prescribing habits across health care facilities. While these have had some success, there is significant room for improvement.
Head and neck cancer (HNC) patients represent a unique population in that surgical resection often leads to significant peri-operative pain and disfigurement. A high proportion, up to 50% of these patients also suffer from psychiatric comorbidities. These factors inherently increase the risk of opioid dependence and studies have shown that chronic opioid use following surgery for HNC is associated with decreased disease free survival. Novel methods are needed to minimize opioid risks in this patient population.
Conditioning therapy aims to elicit a classically conditioned, or Pavlovian, response through consistent pairing of a medication with a neutral stimulus (i.e. an odor). Treatment involves reinforcement with simultaneous presentation of a characteristic odor with each dose of active and inactive medication. Prior studies have shown efficacy of conditioning therapy paired with placebo medication to decrease the total dose of active medications required for a clinical response including opioids for pain following spinal cord injury, stimulants for attention deficit hyperactivity disorder, and corticosteroids for psoriasis. Many of these have been performed as "open-label" studies, where patients were aware of group assignment and were informed when each placebo treatment was given.
These results suggest that patients with HNC may also benefit from conditioned open-label placebos by reducing total opioid consumption required for adequate pain control in the peri-operative setting and providing an innovative intervention to potentially decrease the risk of opioid dependence in this patient population.
Primary Objective:
Determine if the addition conditioned open-label placebo (COLP) to standard multimodal analgesia decreases baseline opioid consumption from post-operative day (POD) 2 to 5 in comparison to standard multimodal analgesia alone in patients with head and neck cancer.
Rationale:
Patients with head and neck cancer will be enrolled in this randomized, controlled, open-label trial. All study participants will receive standard multimodal analgesia, including opioids, and will have daily opioid consumption and pain severity documented following surgery. Patients in the COLP group will additionally receive conditioning (i.e. exposure to clove oil) with each active oxycodone dose on POD 1-5 and a scheduled placebo oxycodone paired with conditioning (i.e. exposure to clove oil) 3 times per day on POD 2-5. The chance in baseline opioid consumption from POD 2 to 5 will be compared between groups.
Secondary Objectives:
Determine if the addition conditioned open-label placebo (COLP) to standard multimodal analgesia leads to a reduction in pain severity following surgery and persistent opioid use at 6-months following surgery in comparison to standard multimodal analgesia alone in patients with head and neck cancer.
Rationale:
Following surgery, patients complete daily surveys on pain severity. The investigators will compare these pain scales between COLP and TAU groups to determine if there is a difference in pain severity between treatment groups. The investigators will also analyze long-term effects of the intervention with COLP. After the second week following surgery, opioid consumption will continue to be recorded by nursing (if inpatient) or with patient reported surveys (after discharge) through 6 months after surgery. While COLP may have immediate effects on opioid consumption during therapy, the goal of this aim is to determine if short-term therapy can result in long-term changes in behavior.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
SUPPORTIVE_CARE
NONE
Study Groups
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Treatment as usual (TAU)
Standard pain regimen with scheduled acetaminophen and ibuprofen, oxycodone as needed for moderate-to-severe pain, and intravenous hydromorphone as needed for breakthrough pain.
Surveys about pain levels, opioid consumption, side effects of opioids, understanding of placebo effect and symptoms of depression.
Surveys about pain, opioid use and depression symptoms
Surveys before surgery: Within 1 week prior to surgery, patients complete surveys about pain levels, opioid consumption, understanding of placebo effect and symptoms of depression.
Surveys after surgery: Through 6-months after surgery, patients complete surveys about pain levels, opioid consumption, side effects of opioids and symptoms of depression.
Conditioned open-label placebo (COLP)
Standard pain regimen with scheduled acetaminophen and ibuprofen, oxycodone as needed for moderate-to-severe pain, and intravenous hydromorphone as needed for breakthrough pain.
Conditioning (i.e. exposure to clove oil scent) with each dose of oxycodone medication on post-operative day (POD) 1-5.
Scheduled placebo oxycodone medication paired with conditioning (i.e. exposure to clove oil scent) 3 times per day on POD 2-5.
Surveys about pain levels, opioid consumption, side effects of opioids, understanding of placebo effect and symptoms of depression.
Conditioned open-label placebo (COLP)
Placebo oxycodone will be formulated to have the same physical appearance as liquid oxycodone and will be dispensed by the inpatient pharmacy and administered by the nursing staff. At all times that oxycodone or placebo medication is administered on post-operative day (POD) 1-5, the patient will undergo conditioning via exposure to a clove oil scent:
1. Conditioning (i.e. exposure to clove oil scent) with each dose of oxycodone medication on POD 1-5.
2. Scheduled placebo oxycodone medication paired with conditioning (i.e. exposure to clove oil scent) 3 times per day on POD 2-5.
Surveys about pain, opioid use and depression symptoms
Surveys before surgery: Within 1 week prior to surgery, patients complete surveys about pain levels, opioid consumption, understanding of placebo effect and symptoms of depression.
Surveys after surgery: Through 6-months after surgery, patients complete surveys about pain levels, opioid consumption, side effects of opioids and symptoms of depression.
Interventions
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Conditioned open-label placebo (COLP)
Placebo oxycodone will be formulated to have the same physical appearance as liquid oxycodone and will be dispensed by the inpatient pharmacy and administered by the nursing staff. At all times that oxycodone or placebo medication is administered on post-operative day (POD) 1-5, the patient will undergo conditioning via exposure to a clove oil scent:
1. Conditioning (i.e. exposure to clove oil scent) with each dose of oxycodone medication on POD 1-5.
2. Scheduled placebo oxycodone medication paired with conditioning (i.e. exposure to clove oil scent) 3 times per day on POD 2-5.
Surveys about pain, opioid use and depression symptoms
Surveys before surgery: Within 1 week prior to surgery, patients complete surveys about pain levels, opioid consumption, understanding of placebo effect and symptoms of depression.
Surveys after surgery: Through 6-months after surgery, patients complete surveys about pain levels, opioid consumption, side effects of opioids and symptoms of depression.
Eligibility Criteria
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Inclusion Criteria
* Scheduled for surgery for resection of and/or reconstruction following resection of a head and neck tumor between November 15, 2022 - May 15, 2024, with expected inpatient admission of at least 5 days after surgery.
* Age 18 years or older
* Ability to comprehend and willingness to participate in open-label conditioning portion of study regardless of study group assignment
* Ability to participate in study for 1 week prior to surgery and 6 months following surgery at time of enrollment
Exclusion Criteria
* Chronic pain (defined as pain lasting \>3 months) or chronic opioid use (for \>3 months).
* Contraindication to receiving acetaminophen, ibuprofen, oxycodone, or hydromorphone
* New gabapentin prescription started \<2 weeks prior to surgery
* Psychosis, delirium or other significant cognitive impairment preventing participation in study
18 Years
ALL
No
Sponsors
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University of Maryland
OTHER
American Academy of Otolaryngology-Head and Neck Surgery Foundation
OTHER
Johns Hopkins University
OTHER
Responsible Party
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Principal Investigators
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Carole Fakhry, MD
Role: PRINCIPAL_INVESTIGATOR
JHU SOM Oto Head and Neck Surgery
Locations
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Johns Hopkins Hospital
Baltimore, Maryland, United States
Countries
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References
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Hill MV, McMahon ML, Stucke RS, Barth RJ Jr. Wide Variation and Excessive Dosage of Opioid Prescriptions for Common General Surgical Procedures. Ann Surg. 2017 Apr;265(4):709-714. doi: 10.1097/SLA.0000000000001993.
Lydiatt WM, Moran J, Burke WJ. A review of depression in the head and neck cancer patient. Clin Adv Hematol Oncol. 2009 Jun;7(6):397-403.
Hill MV, Stucke RS, Billmeier SE, Kelly JL, Barth RJ Jr. Guideline for Discharge Opioid Prescriptions after Inpatient General Surgical Procedures. J Am Coll Surg. 2018 Jun;226(6):996-1003. doi: 10.1016/j.jamcollsurg.2017.10.012. Epub 2017 Nov 30.
Dang S, Duffy A, Li JC, Gandee Z, Rana T, Gunville B, Zhan T, Curry J, Luginbuhl A, Cottrill E, Cognetti D. Postoperative opioid-prescribing practices in otolaryngology: A multiphasic study. Laryngoscope. 2020 Mar;130(3):659-665. doi: 10.1002/lary.28101. Epub 2019 Jun 21.
Buchmann L, Conlee J, Hunt J, Agarwal J, White S. Psychosocial distress is prevalent in head and neck cancer patients. Laryngoscope. 2013 Jun;123(6):1424-9. doi: 10.1002/lary.23886. Epub 2013 Apr 1.
Chan JY, Lua LL, Starmer HH, Sun DQ, Rosenblatt ES, Gourin CG. The relationship between depressive symptoms and initial quality of life and function in head and neck cancer. Laryngoscope. 2011 Jun;121(6):1212-8. doi: 10.1002/lary.21788. Epub 2011 May 3.
Starr N, Oyler DR, Schadler A, Aouad RK. Chronic opioid use after laryngeal cancer treatment. Head Neck. 2021 Apr;43(4):1242-1251. doi: 10.1002/hed.26591. Epub 2020 Dec 28.
Pang J, Tringale KR, Tapia VJ, Moss WJ, May ME, Furnish T, Barnachea L, Brumund KT, Sacco AG, Weisman RA, Nguyen QT, Harris JP, Coffey CS, Califano JA 3rd. Chronic Opioid Use Following Surgery for Oral Cavity Cancer. JAMA Otolaryngol Head Neck Surg. 2017 Dec 1;143(12):1187-1194. doi: 10.1001/jamaoto.2017.0582.
Ader R, Mercurio MG, Walton J, James D, Davis M, Ojha V, Kimball AB, Fiorentino D. Conditioned pharmacotherapeutic effects: a preliminary study. Psychosom Med. 2010 Feb;72(2):192-7. doi: 10.1097/PSY.0b013e3181cbd38b. Epub 2009 Dec 22.
Morales-Quezada L, Mesia-Toledo I, Estudillo-Guerra A, O'Connor KC, Schneider JC, Sohn DJ, Crandell DM, Kaptchuk T, Zafonte R. Conditioning open-label placebo: a pilot pharmacobehavioral approach for opioid dose reduction and pain control. Pain Rep. 2020 Jul 20;5(4):e828. doi: 10.1097/PR9.0000000000000828. eCollection 2020 Jul-Aug.
Sandler AD, Bodfish JW. Open-label use of placebos in the treatment of ADHD: a pilot study. Child Care Health Dev. 2008 Jan;34(1):104-10. doi: 10.1111/j.1365-2214.2007.00797.x.
Shunmugasundaram C, Rutherford C, Butow PN, Sundaresan P, Dhillon HM. What are the optimal measures to identify anxiety and depression in people diagnosed with head and neck cancer (HNC): a systematic review. J Patient Rep Outcomes. 2020 Apr 23;4(1):26. doi: 10.1186/s41687-020-00189-7.
Gloth FM 3rd, Scheve AA, Stober CV, Chow S, Prosser J. The Functional Pain Scale: reliability, validity, and responsiveness in an elderly population. J Am Med Dir Assoc. 2001 May-Jun;2(3):110-4.
Arnstein P, Gentile D, Wilson M. Validating the Functional Pain Scale for Hospitalized Adults. Pain Manag Nurs. 2019 Oct;20(5):418-424. doi: 10.1016/j.pmn.2019.03.006. Epub 2019 May 14.
Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x.
Zung WW. A rating instrument for anxiety disorders. Psychosomatics. 1971 Nov-Dec;12(6):371-9. doi: 10.1016/S0033-3182(71)71479-0. No abstract available.
Cometto-Muniz JE, Cain WS, Abraham MH. Determinants for nasal trigeminal detection of volatile organic compounds. Chem Senses. 2005 Oct;30(8):627-42. doi: 10.1093/chemse/bji056. Epub 2005 Sep 1.
Trakimas DR, Colloca L, Fakhry C, Tan M, Khan Z, Vosler PS. Study protocol: randomised controlled trial of conditioned open-label placebo (COLP) for perioperative pain management in patients with head and neck cancer. BMJ Open. 2023 Jul 7;13(7):e069785. doi: 10.1136/bmjopen-2022-069785.
Other Identifiers
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IRB00276225
Identifier Type: -
Identifier Source: org_study_id
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