Reducing Opioid Use and Misuse After Wisdom Molar Extractions

Reducing Opioid Use/Misuse Through Better Pain Control and Active Pill Dispensing

Reducing opioid prescription related use and misuse is a major focus for countering the national epidemic of opioid overdose and death. Annually, over 3.5 million predominantly young and healthy individuals undergo outpatient third molar ('wisdom tooth') tooth extractions under sedation and routinely receive postoperative opioid prescriptions. This procedure is among the most prevalent instances of opioid prescriptions dispensed to adolescents, a vulnerable population. This overuse can be minimized by bringing about immediate and sustained pain relief following extractions and by proper monitoring to regulate post-operative opioid usage.

The investigators developed the Twin block, a local anesthetic nerve block that rapidly eases pain from the 'closer' muscles of the jaw and showed its long-term effectiveness in patients with chronic jaw muscle pain. Administering the Twin block immediately following third molar extractions will be an innovative and effective modality to alleviate acute post-procedure pain experienced by the patient and hence reduce the need for post-operative opioid pain medication.

In order to tightly regulate when, how many and to whom the prescribed opioid pill is accessible, this study will utilize the iPill Dispenser®, an active pill dispenser. The iPill device, designated as a Class I 510(k) exempt device by the FDA, includes an App that utilizes biometric user authentication to operate a portable tamper-resistant, pre-calibrated device to regulate, deliver, and monitor opioid usage for pain, preventing overconsumption and diversion. The investigators further plan to 'track' pill swallowing by encapsulating the medication with an ingestible event marker (IEMs, FDA approved Class II device). The hypothesis of this study is that reduction in opioid prescription and its unwarranted use following third molar extractions can be achieved by a combination of Twin block, an active pill dispenser and ingestion tracking. The Specific Aims are:

Specific Aim 1. Compare highest pain after third molar tooth extractions, in patients with and without the twin block.

Specific Aim 2. Compare postoperative opioid consumption during the first 4 days following third molar tooth extractions between patients who got the twin block, with those who do not. Using the iPill dispenser and app and the IEM, the investigators will track opioid consumption for severe pain.

Study Overview

• Status: Not yet recruiting
• Conditions: Pain, Postoperative
• Intervention / Treatment: Drug: Twin block; Device: iPill dispenser

Detailed Description

Reducing opioid prescription related use and misuse is a major focus for countering the national epidemic of opioid overdose and death. Annually, over 3.5 million predominantly young and healthy individuals undergo outpatient third molar ('wisdom tooth') tooth extractions and routinely receive postoperative opioid prescription (Moore, Nahouraii et al. 2006). This procedure is among the most prevalent instances of opioid prescriptions dispensed to adolescents and is the subject of a national debate, given the risk for persistent opioid use and abuse in a vulnerable population (Volkow, McLellan et al. 2011, Dowell, Haegerich et al. 2016, Groenewald, Rabbitts et al. 2016, Moore, Dionne et al. 2016, Harbaugh, Nalliah et al. 2018). The investigators believe that this overuse can be minimized by bringing about immediate and sustained pain relief following extractions and by proper monitoring to regulate post-operative opioid usage.

Prolonged mouth opening as well as eccentric and isometric contractions, as are typical during third molar tooth extraction procedures, can result in acute muscle pain in the masticatory or 'chewing' muscles. However, it is common practice to numb only the actual tooth extraction site for postoperative pain management, without evaluating for and addressing acute post-procedure muscle pain. The investigators' preliminary studies have corroborated the efficacy of the Twin block, a local anesthetic, in the diagnosis and management of acute and chronic myogenous orofacial pain stemming from the 'chewing muscles' (Quek, Young et al. 2014, Kanti, Ananthan et al. 2017). The investigators expect that administering the Twin block immediately following third molar extractions, will be an innovative and effective modality to alleviate acute post-procedure pain experienced by the patient and hence reduce the need for post-operative opioid pain medication. Our hypothesis, therefore, is that reduction in opioid prescription and unwarranted use can be achieved by a combination of Twin block and an actively monitored pill dispenser. We have selected the iPill Dispenser® to monitor and regulate post-operative usage.

The iPill device includes an App that utilizes biometric user authentication to operate a portable tamper-resistant, pre-calibrated device to regulate, deliver, and monitor opioid usage for pain, preventing overconsumption and diversion. Coencapsulating the pain pill with the IEM will create a virtual 'time-stamp' by triggering a wireless signal from the IEM, when contacted by stomach acid content, which is detected by a sensor secured on the skin with an adhesive strip.

Therefore, the Specific Aims are:

Specific Aim 1. Compare peak postoperative pain after third molar tooth extractions, with and without the twin block, in a randomized blind prospective clinical study Patients undergoing third molar tooth extractions under 'moderate' (intravenous) sedation, will be randomized to receive either the twin block or a sham injection on the side of their extraction/s. The Twin block and sham injection groups will be compared for peak postoperative pain measured using the numerical pain rating scale (NRS). The investigators predict at least a 50% reduction in percentage of patients reporting significant pain (NRS≥5), in the group randomized to receive the twin block.

Specific Aim 2. Compare postoperative opioid consumption during the first 96 hours following third molar tooth extractions between patients randomized to the control or twin block groups Using the iPill dispenser and app, the investigators will track IEM-co-encapsulated opioid consumption for severe pain among patients randomized to either the sham or Twin block arms. The investigators predict at least a 30% reduction in opioid consumption for severe pain in the group randomized to receive the Twin block. The investigators expect that utilizing the iPill dispenser® and app will enforce rigorous, real-time and accurate monitoring of opioid usage for pain management, overcoming the traditional reliance on patient-reported usage.

POSSIBLE OUTCOMES: This research will potentially transform conventional postoperative pain management following third molar ('wisdom' tooth) extractions. The investigators expect the routine incorporation of the twin block to alleviate post-operative pain, thereby reducing the current reliance on opioid prescriptions in a vulnerable population, especially after a commonplace procedure.

• Study Type: Interventional
• Enrollment (Estimated): 133
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gayathri Subramanian, PhD, DMD; Phone Number: 973 972 3418; Email: subramga@sdm.rutgers.edu
• Study Contact Backup: Name: Anayo Adachie, DMD, MD; Phone Number: 732 235 5050; Email: aoa80@sdm.rutgers.edu

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Health University Dental Associates
      • Contact: Anayo Adachie, DMD, MD; Phone Number: 732-235-5050; Email: aoa80@sdm.rutgers.edu
      • Sub-Investigator: Samuel YP Quek, DMD, MPH
      • Sub-Investigator: Shuying Jiang, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Adults (> 18)
2. American Society of Anesthesiologists Classification I
3. No h/o temporomandibular disorder (TMD) symptoms
4. No h/o trauma to jaws/teeth
5. No h/o surgery in maxillofacial region
6. Presenting for extraction of at least 1 mandibular partially bony/ full bony impacted 'wisdom' or third molar/s under intravenous sedation
7. iPhone or Android smart phone (compatible with iPill® App)
8. Informed consent
9. No cognitive/intellectual disability
10. Not from vulnerable population

Exclusion Criteria:

1. Acute infection or pain in relation to the impacted molars on day of procedure
2. h/o opioid prescription for acute/chronic pain
3. h/o of allergy or contraindication to amide-type local anesthetics, epinephrine or opioids
4. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs)/muscle relaxants/other prescriptions to manage pain/inflammation
5. Refusal/inability to use iPill® App or dispenser
6. h/o eczema

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Twin Block local anesthetic; Patients undergoing extractions of lower wisdom molar/s under intravenous sedation will receive the Twin block local anesthetic (using the standard dental anesthetic 1.8 cc 2% lidocaine with 1:100,000 epinephrine), once, on the side/s of their extraction/s	Drug: Twin block; Dental local anesthetic administered to target the jaw 'closer' muscles, temporalis and masseter; Device: iPill dispenser; An active pill dispenser, regulated by patient's pain score entered on an iPill App installed on their smart phone (iPhone, Android) to dispense opioid (for pain corresponding to severe pain) or prescription strength ibuprofen and acetaminophen (for moderate pain), with over the counter solutions for mild pain recommended. This pill dispenser will be given to all patients, in both Twin block and Control groups, to regulate and monitor their pain experience-driven pain medication regimen. The pill dispenser will be packaged with pain medication (1 dispenser with vicodin, 1 with prescription ibuprofen, 1 with acetaminophen) that has been coencapsulated with ingestible event markers (IEMs, Proteus Discover).; Other Names: Active pill dispenser
Sham Comparator: Control; Patients undergoing extractions of lower wisdom molar/s under intravenous sedation will receive the Twin block injection but with no medication administered/dispensed from the syringe, on the side/s of their extraction/s	Device: iPill dispenser; An active pill dispenser, regulated by patient's pain score entered on an iPill App installed on their smart phone (iPhone, Android) to dispense opioid (for pain corresponding to severe pain) or prescription strength ibuprofen and acetaminophen (for moderate pain), with over the counter solutions for mild pain recommended. This pill dispenser will be given to all patients, in both Twin block and Control groups, to regulate and monitor their pain experience-driven pain medication regimen. The pill dispenser will be packaged with pain medication (1 dispenser with vicodin, 1 with prescription ibuprofen, 1 with acetaminophen) that has been coencapsulated with ingestible event markers (IEMs, Proteus Discover).; Other Names: Active pill dispenser

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numerical Pain Rating Scale score (NRS)	Scale from 0 to 10 used to describe no pain (0), mild pain (1-3), moderate (4-6) and severe (7-10) pain. Collection of peak post-procedure, mean, median, quartile pain scores	Change in NRS pain scores between baseline and 96 hours post-pain regimen assignment
Pain medication consumed (mg)	Dosage of combination opioid, ibuprofen and acetaminophen consumed	Through 96 hours post-procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	As described by patients	During the first 4 days following procedure
iPill Dispenser performance- Validation of pills dispensed	Validation of pills dispensed- correlation between expected and actual number of remaining pills in each dispensers	During the first 4 days following procedure
iPill Dispenser performance- Incidence of dispenser tampering	Detection of tampering upon inspection of returned dispensers	During the first 4 days following procedure
iPill Dispenser performance- Incidence of failure of operability	Frequency of failed pill dispensing	During the first 4 days following procedure
iPill Dispenser performance- Percentage of returned dispensers	Percentage of dispensers returned during post-operative visit	During the first 4 days following procedure
IEM relayed record of pill ingestion	Log of pills ingested as relayed to IEM App	During the first 4 days following procedure

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: iPill Dispenser
• Investigators: Principal Investigator: Gayathri Subramanian, PhD DMD, Rutgers School of Dental Medicine; Principal Investigator: Anayo Adachie, DMD, MD, Rutgers School of Dental Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: May 21, 2020
• First Submitted That Met QC Criteria: May 31, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Impacted third molar extraction; Acute pain management; Active pill dispenser; Opioid misuse reduction
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative
• Other Study ID Numbers: Pro2019002739; 1 R21 DA051212-01 (Other Identifier: NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

At this time, we have made the commitment to share aggregate data.(We will consider releasing anonymized individual data upon a case by case documented request that the data is being sought for an appropriate reason).

With our study design, our basic data will be collected 1. at site of care (dental clinic) and 2. Remotely. Remote data on the app will only be linked with an enrollment number because that data will be collated by our collaborator (Consultant: iPill) and hence will be devoid of identifiers. CRFs will contain data pooled from all the time points in the study and identified only by an enrollment number that will not provide any identifiers. Hence, we will be able to commit to releasing all data collected in this study without compromising patient confidentiality.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No