Methadone Loading Dose Initiation for Hospitalized Patients with Opioid Use Disorder Using Fentanyl

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

Project Summary/Abstract Candidate: Ashish Thakrar, MD, MS, is an addiction medicine specialist, internal medicine physician, and clinician-scientist committed to improving care for individuals with substance use disorders (SUDs). His career goal is to become an independent investigator developing and adapting safe, effective, and patient-centered pharmacotherapy for SUDs in the era of synthetic drugs. Career Development Plan: To achieve this career goal, Dr. Thakrar will pursue coursework, seminars, externships, and individualized instruction in four specific areas: (1) the behavioral pharmacology of addiction; (2) responsible design and conduct of clinical trials for SUDs; (3) recruitment, assessment, and retention of hospitalized patients for prospective research; and (4) qualitative and survey methods to assess patient experiences in SUD treatment. These training goals are closely aligned with the research aims in this proposal. Research Context: Each year, there are 500,000 medical or surgical hospitalizations for patients with opioid use disorder (OUD), yet outcomes for these hospitalizations are poor: untreated withdrawal is common, patient satisfaction is low, 11-17% of patients leave before medically advised, and less than 10% are discharged on medications for OUD. While methadone at adequate doses treats opioid withdrawal, prevents before medically advised discharges, and reduces mortality, there is little evidence on how to dose methadone to start treatment for OUD with fentanyl use (“fentanyl OUD”). The traditional outpatient dosing approach to methadone initiation does not consistently treat fentanyl withdrawal and takes weeks of titration to reach therapeutic doses. Given methadone's long half-life, a “loading dose” approach could be a safe and effective alternative in the hospital. Specific Aims: The goal of this proposal is to rigorously develop and pilot test a methadone loading dose approach to starting treatment for fentanyl OUD in the hospital. Aim 1: To conduct a dose-finding study to identify the maximum tolerated methadone loading dose appropriate for future study among persons with fentanyl OUD. Aim 2: To conduct a randomized pilot trial of methadone loading dose initiation among hospitalized patients with fentanyl OUD. Aim 2A is to assess trial feasibility, clinical outcomes, and safety; Aim 2B is to assess patient acceptability and other patient-centered outcomes with interviews and a survey. Mentorship Team: Dr. Thakrar has assembled a team of mentors, advisors, and consultants with extensive experience supervising research and with complementary expertise in behavioral pharmacology, clinical trials of OUD pharmacotherapy, hospital-based prospective research, and patient-reported outcomes research. Environment: The University of Pennsylvania and Penn Medicine offer an ideal environment to pursue this training and research. Dr. Thakrar will succeed because of the support of an experienced and dedicated mentorship team, outstanding research infrastructure, and extensive resources for professional development.