Conditioned Open-label Placebo (COLP) for Peri-operative Pain Management in Patients With Head and Neck Cancer

NCT04973748 | Completed

• 1 other identifier: IRB00276225
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The opioid epidemic is a considerable problem in the United States, and prescription opioids significantly contribute to the epidemic. Head and neck cancer (HNC) patients are inherently at increased risk for opioid dependence as surgical treatment can cause significant pain and up to 50% of patients also suffer from psychiatric comorbidities. Novel methods are needed to decrease opioid consumption following HNC surgeries to limit the risk of chronic opioid dependence in these patients. Conditioning therapy with placebo aims to elicit a classically conditioned response to an inactive medication through consistent pairing of the medication with a neutral stimulus (i.e. an odor) and has been shown to be effective for decreasing the amount of active drug require for certain clinical responses, including for acute pain. However, studies have not been completed for the treatment of acute pain in the inpatient post-operative setting. The overall goal of this pilot study is to determine the feasibility and effectiveness of conditioned open-label placebo (COLP) as an adjunct for post-operative pain management in complex head and neck cancer patients. This randomized, controlled, open-label trial will specifically compare post-operative opioid consumption and pain scales between patients receiving multimodal analgesia along with conditioned open-label placebo (COLP group) to those receiving multimodal analgesia, alone (Treatment as usual group). Findings from this study will determine the efficacy of COLP as an innovative approach to decrease opioid consumption and improve pain control in head and neck cancer patients and will provide rationale for development of future large scale trials.

Conditions

Postoperative Pain; Opioid Use

Keywords

open label placebo; opioid; postoperative analgesia; placebo; head and neck cancer

Outcome Measures

Primary Outcomes (1)

• Change in baseline daily morphine milligram equivalents (MME/day)

  Comparison of average daily MME on POD 5 to average daily MME on POD 2 between TAU and COLP groups.

  once after surgery up to 1 week

Secondary Outcomes (5)

• Change in Pain assessed by Visual Analogue Scale

  daily after surgery up to 2 weeks, then weekly daily after surgery up to 1 month, then monthly daily after surgery up to 3 months, then once daily after surgery up to 6 months

• Change in Pain as assessed by the Functional Pain Scale

  daily after surgery up to 2 weeks, then weekly daily after surgery up to 1 month, then monthly daily after surgery up to 3 months, then once daily after surgery up to 6 months

• Change in Depression as assessed by the Patient Health Questionnaire-9 (PHQ-9)

  weekly daily after surgery up to 1 month, then monthly daily after surgery up to 3 months, then once daily after surgery up to 6 months

• Change in Numerical Opioid Side Effects (NOSE)

  daily after surgery up to 2 weeks, then weekly daily after surgery up to 1 month, then monthly daily after surgery up to 3 months, then once daily after surgery up to 6 months

• Persistent opioid consumption at 6 months after surgery

  once after surgery up to 6 months

Study Arms (2)

Treatment as usual (TAU)

ACTIVE COMPARATOR

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.

Behavioral: Surveys about pain, opioid use and depression symptoms

Conditioned open-label placebo (COLP)

EXPERIMENTAL

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.

Behavioral: Conditioned open-label placebo (COLP); Behavioral: Surveys about pain, opioid use and depression symptoms

Interventions

Conditioned open-label placebo (COLP) BEHAVIORAL

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.

Conditioned open-label placebo (COLP)

Surveys about pain, opioid use and depression symptoms BEHAVIORAL

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); Treatment as usual (TAU)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients receiving pre-operative evaluation for head and neck cancer in the Otolaryngology - Head and Neck Surgery Department at Johns Hopkins Hospital
• 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

You may not qualify if:

• Past medical history of substance use disorder
• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• University of Maryland: collaborator
• American Academy of Otolaryngology-Head and Neck Surgery Foundation: collaborator

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Related Publications (18)

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• 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.

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  PMID: 16141291 BACKGROUND

• 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.

  PMID: 37419646 DERIVED

MeSH Terms

Conditions

Pain, Postoperative; Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Neoplasms by Site; Neoplasms

Study Officials

• Carole Fakhry, MD

  JHU SOM Oto Head and Neck Surgery

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized controlled trial

Study Record Dates

• First Submitted: July 9, 2021
• First Posted: July 22, 2021
• Study Start: February 7, 2023
• Primary Completion: June 28, 2024
• Study Completion: June 28, 2024
• Last Updated: August 23, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)