Improving Pain Management and Opioid Safety for Patients With Cirrhosis: Pilot Program
Phase: NA
Conditions: Cirrhosis, Liver
Sponsor: University of Pittsburgh

Page 1 of 5 
 
Study Protocol  
 
 
 
 
 
 
Official Title: Improving Pain Management and Opioid Safety  
for Patients With Cirrhosis: Pilot Program 
  
 
 
ClinicalTrials.gov ID (NCT number): NCT05128578 
 
 
 
Protocol Date: April 17, 2023 
 
 
 
 

Page 2 of 5 
 
Scientific Background 
Approximately 79-86% of patients with cirrhosis have chronic pain, and nearly two-thirds of 
patients with cirrhosis and pain are prescribed opioid medications each year, often in a manner 
inconsistent with opioid safety guidelines. The PI’s previous observational studies investigated 
the factors associated with pain and opioid use in patients with liver disease, and have 
highlighted how our current management of pain in this population affects clinical outcomes. 
The PI also found that, in patients with chronic liver disease (CLD), pain and opioid use are 
associated with increased hospitalizations and hepatology clinic visits, and that patients with 
cirrhosis often meet criteria for fibromyalgia even in the absence of hepatitis C. This led to 
investigations showing that pain and opioid use are associated with hospitalization in this 
population. 
 
Preliminary work was completed to identify the needs of the patient population. Barriers to pain 
self-management for patients with cirrhosis included the complexity of pain management, 
absence of evidence-based intervention, and inadequate provider knowledge, time and training. 
The research team developed an intervention as the result of stakeholder input. 
 
The PI also led a national survey of transplant centers to assess practices and policies around 
opioid use and opioid substitution therapy. In addition, she found that nearly half of Veterans 
with cirrhosis were prescribed opioids, and opioid prescriptions were associated with increased 
mortality (manuscript in progress). 
 
This body of work has identified the scope of opioid use in individuals with CLD, the 
hospitalization associated with opioid use in this population, and policies to address opioid and 
opioid substitution therapy. 
 
Despite the high prevalence of pain and its adverse consequences in patients with cirrhosis, there 
is limited guidance on how to manage pain in this patient population. Without understanding the 
barriers and facilitators affecting patients with cirrhosis and chronic pain, it remains unclear how 
to improve outcomes. The data provided by this study will help guide efforts to develop a safe, 
effective approach to managing pain in patients with cirrhosis. 
 
 
Study Objectives 
The purpose of this study is to conduct a pilot trial of a pain self-management intervention for 
patients with cirrhosis. The Liver Education About Pain (LEAP) intervention is a 12-week 
program that involves individual and group sessions with a health coach. The goal is to assess 
and optimize the intervention’s feasibility and acceptability prior to conducting an efficacy trial, 
since no pain management interventions have been tested in this patient population. 
 
 
Study Design & Methods 
This interventional study with a pre-post design. Assessments will be completed either in-person 
(using a paper or electronic survey/app), online with a URL, or over the phone, based on patient 

Page 3 of 5 
 
preference. Any in-person assessments will be completed in conjunction with a scheduled CLD 
visit, for the convenience of patients. 
 
Research Procedures 
Participants will go through a 6-week one-on-one behavioral intervention, followed by optional 
group sessions (n=6 weekly sessions). They will also complete assessment surveys/interviews 
conducted at multiple time points (baseline, end of 6 weeks, end of 12 weeks, and post 
intervention followup), each taking 30-60 minutes. All participants will receive their usual care 
from their hepatology team. This study will not impact their normal clinic care. 
 
Intervention 
Liver Education About Pain (LEAP) is a 12-week intervention involving weekly meetings with a 
health coach (“Pain Coach”), with 6 weeks of individual sessions and 6 weeks of optional group 
sessions. Timing for beginning the group sessions may vary to accommodate an adequate 
number of participants (ideally 3 or more) into the group, such that some individual session 
weeks may overlap with group session weeks. Each session will last approximately 1 hour. If 
participants miss a session, there will be the option to reschedule. As participants are consented 
and enrolled in the study, they will complete the baseline assessment and then be scheduled for 
their individual sessions with the Pain Coach. 
 
Manual  
The LEAP manual will be a guide to the intervention and used by the participants during the 
trial. Individual and group sessions will follow the LEAP manual. Topics to be addressed include 
an introduction to chronic pain and cirrhosis, physical activity, losing weight to improve pain, 
stress management, sleeping better, thinking differently about pain, talking with friends and 
family about pain, taking opioid pain medications, and coping with pain without drugs and 
alcohol. LEAP manuals will not be collected as part of the study; however, participants will tell 
the Pain Coach what they’ve been doing per the manual and in the “homework” sections. 
 
Pain Coach  
The Pain Coach will lead all sessions and take attendance as needed for the feasibility 
assessment post-intervention.  
 
Individual Sessions  
At the start of each individual session, the Pain Coach will go through the three-question PEG 
scale to keep a data set of each participants’ pain week-to-week. Participants will pick topics 
they want to do and go through them with the Pain Coach, learn about new ways to improve on 
what they’ve already been doing, and keep track of what they’ve learned and how they’re doing 
with their pain. 
 
Group Sessions  
The optional group sessions will provide a platform where patients will talk about how the 
individual sessions went and what tools were helpful. They will be able to learn from each other 
and get additional input from the Pain Coach. 
 

Page 4 of 5 
 
Assessments  
The research team will collect assessments from patients at the following timepoints: 
• Survey at enrollment (baseline) 
• Survey 6 weeks after the start of the intervention, i.e., after completion of individual 
sessions 
• Survey & interview 12 weeks after the start of the intervention, i.e., after conclusion of 
group sessions 
• Survey 3-months post-intervention (or 24 weeks after the start of the intervention, i.e., 12 
weeks after conclusion of group sessions) 
 
Assessments are expected to last 30-60 minutes each and will include a combination of medical 
record data and patient-reported outcomes. At baseline, patients will report demographic data, 
and at follow-up we will collect additional feasibility and acceptability data. 
 
Audio Recording 
Group and individual sessions will be audio recorded and de-identified to assess fidelity. 
Assessment surveys will be offered online, on paper, or by phone, as is most convenient for 
patients. Assessment interviews will take place virtually or by phone. Any phone calls/virtual 
meetings to collect data will be recorded and the transcripts of the calls will be subsequently de-
identified. 
 
 
Eligibility Criteria  
 
Inclusion Criteria 
All participants must be ≥18 years of age and fluent in English. Additional specific inclusion 
criteria include: 
• Diagnosis of cirrhosis 
• Receiving care at UPMC hepatology clinics 
• Chronic pain 
 
Exclusion criteria 
Participants will be excluded if they are <18 years of age or are unable to provide informed 
consent for any reason. Additional exclusion criteria include: 
• Prior liver transplantation 
• Limited life expectancy (<6 months) 
 
 
Analysis Plan and Statistical Considerations 
The goal of this pilot study is to determine feasibility and acceptability outcomes in preparation 
for a larger trial. Emerging consensus, including NIH guidance, recommends against assessing 
preliminary efficacy in pilot studies, since small pilot sample sizes lead to imprecise estimates. 
The analysis will include summary statistics, including change in measures using appropriate 
analysis. Primary outcomes will include completion of at least 80% of individual sessions and 
satisfaction with intervention, measured using the TEQ (Likert-scale based assessment of 5 

Page 5 of 5 
 
domains of satisfaction.) The former will be assessed using count data and the latter with means 
and standard deviations. Secondary analyses that include changes in scores over time will 
employ paired t-tests to measure within person change pre to post intervention.