The Application of Lifestyle Enhancing Validated Integrative Therapies for Everyday Pain in Cirrhosis (ALLEVIATE-C)

The goal of this clinical trial is to test a low-touch vs high-touch drug-free pain self-management program that may help lower pain and improve quality of life for adults with cirrhosis and pain. Participants are assigned by chance to one of two study groups. The groups receive different levels of support. The main questions it aims to answer are:

• Do the programs help lower pain?
• Do the programs improve quality of life?
• Is one program more effective than the other?

Researchers will compare a low-touch self management program to a high-touch self-management program to see if the programs help manage pain.

Participants in the low-touch arm will:

• Learn new ways to manage pain without medication
• Receive access to the self-guided digital self-management platform
• Receive general behavioral text message nudges
• Receive a free Fitbit to keep

Participants in the high-touch arm will:

• Learn new ways to manage pain without medication
• Receive tailored access to the self-guided digital self-management platform
• Received individualized pain coaching and optional group coaching sessions
• Participate in a structured walking or meditation curriculum
• Receive a free Fitbit to keep

Study Overview

• Status: Not yet recruiting
• Conditions: Cirrhoses, Liver
• Intervention / Treatment: Behavioral: High-touch self-management program; Behavioral: Low-touch self-management program

Detailed Description

The Application of Lifestyle Enhancing Validated Integrative Therapies for Everyday Pain in Cirrhosis (ALLEVIATE-C) is a multicenter, individual-level, parallel-arm, 1:1 randomized superiority trial with a 4-week run-in period followed by 48 weeks of intervention and follow-up. The study will compare effectiveness of a high-touch vs low-touch self-management program to treat chronic pain among patients with cirrhosis.

Participants in the high-touch arm receive tailored digital self-management program, individualized pain coaching, and a structured walking or meditation curriculum selected through Active Choice as the primary behavioral focus for 48 weeks. The high-touch arm also includes on-demand coaching for low-pain self-efficacy and optional group coaching sessions.

Participants in the low-touch arm receive access to the self-guided digital self-management platform with automated educational content and behavioral nudges for 48 weeks.

Remote or in-person follow up study visits will occur at 12, 24, 36, and 48 weeks.

Endpoints include:

• Primary: Change from baseline in pain interference over 48 weeks (measured using the Pain, Enjoyment of Life, and General Activity (PEG) scale).
• Secondary: Health-related quality of life, cognitive function, average daily step count, pain-related disability, nociplastic pain, cumulative exposure to potentially risky medications, days alive and out of the hospital, pain management strategies, intervention engagement, and care partner burden.
• Implementation: Acceptability, feasibility, intervention fidelity, and barriers and facilitators to implementation.

• Study Type: Interventional
• Enrollment (Estimated): 625
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
      • Contact: Rayshawnda Davis, MS; Email: rayshawnda.davis@ucsf.edu
      • Principal Investigator: Jessica Rubin, MD, MPH
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
      • Principal Investigator: David Goldberg, MD
      • Contact: Cindy Delgado; Phone Number: 305-243-5799; Email: cdelgado5@med.miami.edu
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • John Hopkins University
      • Contact: Lisa Datta; Phone Number: (443) 831-1940; Email: ldatta1@jh.edu
      • Principal Investigator: Alexandra Strauss, MD, PhD
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
      • Principal Investigator: Elliot Tapper, MD
      • Contact: Samantha Nikirk, MPH; Phone Number: 7342324182; Email: samjwalk@med.umich.edu
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
      • Principal Investigator: Douglas Simonetto, MD
      • Contact: Amy Olofson, RN; Phone Number: (507) 538-6547; Email: olofson.amy@mayo.edu
  • New York
    • New York, New York, United States, 10032
      • Columbia University
      • Principal Investigator: Elizabeth Verna, MD
      • Contact: Geena Heitmann, MPH; Phone Number: (212) 305-3839; Email: gg2827@cumc.columbia.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
      • Contact: Richard Mason, PharmD; Phone Number: 215-349-8986; Email: Richard.Mason@pennmedicine.upenn.edu
      • Contact: Jacqueline Theroux, MPH; Phone Number: 2156623904; Email: Jacqueline.Theroux@pennmedicine.upenn.edu
      • Principal Investigator: Marina Serper, MD, MS
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
      • Contact: Ashley Spann, MD, MS; Phone Number: (615) 421-6137; Email: ashley.spann@vumc.org
      • Principal Investigator: Ashley Spann, MD, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Patient Inclusion Criteria:

1. Age > 18 years of age.

2. Clinical diagnosis of cirrhosis established by any one of the following:

   1. Liver biopsy consistent with cirrhosis.

   2. Noninvasive evidence of cirrhosis, defined as ≥2 of the following criteria:

      • Imaging (Ultrasound (US), Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)) demonstrating cirrhosis liver morphology (e.g., 'cirrhosis', cirrhotic appearing', 'nodular') with supportive findings (e.g., splenomegaly or recanalized umbilical vein).
      • Transient elastography (TE) (FibroScan) liver stiffness > 12.5 kilopascal (kPa) with IQR/Median <30% or Magnetic resonance elastography > 5.0 kPa
      • Laboratory evidence including AST/platelet ratio index (APRI) >2.0, FIB-4 >2.67 or Platelet count <150 x 10⁹/L.
      • CT, MRI, or Esophagogastroduodenoscopy (EGD) showing the presence of esophageal varices
   3. History of at least one cirrhosis complication, including variceal hemorrhage, hepatocellular carcinoma (HCC), ascites, or hepatic encephalopathy.
3. Liver transplant recipients are eligible if the transplanted cirrhotic allograft meets the above criteria.
4. Chronic pain, defined as a Pain, Enjoyment of Life, and General Activity (PEG) scale score > 4, assessed during screening prior to consent.
5. Ability to ambulate (walk), either independently or with the use of assistive devices.
6. Reliable access to Wi-Fi or cellular data.
7. Ownership of, or reliable access to, a smartphone with the ability and willingness to receive study-related text messages.
8. Ability to speak and read English or Spanish.

Patient Exclusion Criteria:

1. Acute pain due to injury (e.g., surgery, fracture, trauma, burn) within 28 days.
2. Diagnosed or suspected noncirrhotic portal hypertension.

3. Episode of overt hepatic encephalopathy (HE) within 28 days prior to consent.

   a. Overt HE is defined as acute disorientation requiring hospitalization or initiation of HE-directed therapy (e.g., lactulose, fluids, rifaximin) with diagnosis made by a gastroenterologist, hepatologist, or study investigator and resolution following therapy.

4. Model for End-Stage Liver Disease - Na (MELD-Na) score > 25 calculated using the UNOS algorithm.

   a. Participants with MELD-Na > 25 due to clinically stable end-stage renal disease (ESRD) may be eligible if total bilirubin < 5 mg/dL.

5. Advanced hepatocellular carcinoma (HCC) defined as Barcelona Clinic Liver Cancer (BCLC) stage > C, or current treatment with systemic therapy for HCC (e.g., sorafenib, atezolizumab/bevacizumab, durvalumab/tremelimumab, regorafenib, cabozantinib).
6. > 2 paracenteses within 56 days prior to consent.
7. Fontan-associated liver disease without cirrhosis on biopsy.
8. Inpatient hospital admission lasting > 24 hours within 28 days prior to consent.
9. Active metastatic solid malignancy or acute leukemia within 3 years prior to consent.
10. Estimated life expectancy < 1 year, as determined by the study investigator.
11. Planned living donor liver transplantation within 12 weeks of enrollment.
12. Routine meditation practice, defined as meditation occurring weekly or more frequently.
13. Inability to participate in study procedures, including inability to read study materials, cognitive impairment, or psychiatric illness that would preclude participation in the opinion of the investigator.
14. Concurrent enrollment in another nonpharmacologic pain management study or formal pain management program utilizing nonpharmacologic approaches.
15. Deemed unsuitable for participation by the study investigator.
16. Prisoners.

Care Partner Inclusion Criteria

1. Age > 18 years of age.
2. Informal caregiver of a participant enrolled in ALLEVIATE-C
3. Ability to speak and read English or Spanish.

Care Partner Exclusion Criteria

1. Inability to participate in study procedures, including inability to read study materials, cognitive impairment, or psychiatric illness that would preclude participation in the opinion of the investigator.
2. Deemed unsuitable for participation by the study investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-Touch; Participants receive tailored digital self-management program, individualized pain coaching, and a structured walking or meditation curriculum selected through Active Choice as the primary behavioral focus for 48 weeks. The high-touch arm also includes on-demand coaching for low-pain self-efficacy and optional group coaching sessions.	Behavioral: High-touch self-management program; Tailored digital self-management program, individualized pain coaching, and a structured walking or meditation curriculum selected through Active Choice as the primary behavioral focus for 48 weeks. On-demand coaching for low-pain self-efficacy and optional group coaching sessions.
Experimental: Low-Touch; Participants receive access to the self-guided digital self-management platform with automated educational content and behavioral nudges for 48 weeks.	Behavioral: Low-touch self-management program; Access to the self-guided digital self-management platform with automated educational content and behavioral nudges for 48 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Interference	Change from baseline in pain interference over 48 weeks, measured by repeated assessments using the Pain, Enjoyment of life, and General activity (P.E.G.) scale at 12, 24, 36, and 48 weeks, and compared between the two groups. The PEG is a three-item scale with a minimum value of 0 and a maximum value of 10 for each question. A higher score indicates a worse outcome.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-related quality of life	Change from baseline in health-related quality of life over 48 weeks, assessed using the PROMIS-29+2 Profile v2.1 (PROPr) domain T-scores (physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, and pain interference) as well as the multidomain PROPr summary score. Most domains of the PROPr are ranked on a scale with a minimum of 1 and a maximum of 5. Scores for domains are assessed differently. For fatigue, anxiety, depression, sleep disturbance, and pain interference, a higher score indicates a worse outcome. For physical function, cognitive function, and ability to participate in social roles, a higher score indicates a better outcome. Pain intensity is separately ranked on a scale of 0 to 10, with a higher score indicating a worse outcome.	48 weeks
Average daily step count	Change from baseline in average daily step count over 48 weeks, captured via wearable fitness trackers (Fitbit).	48 weeks
Pain-related disability	Change from baseline in pain-related disability at 48 weeks, measured by the Pain Disability Index (PDI) total score. The PDI is a 7-item scale with a minimum value of 0 and a maximum value of 10 for each question. A higher score indicates a worse outcome.	48 weeks
Severity of nociplastic pain	Change from baseline in severity of nociplastic pain over 52 weeks, assessed using the Fibromyalgia Severity Score (FSS).	52 weeks
Cumulative exposure to potentially risky medications	Change from baseline in cumulative exposure to potentially risky medications over 48 weeks, quantified using the Opioid Total Standardized Dose (TSD) across medication classes relevant to cirrhosis.	48 weeks
Days alive and out of the hospital	Days alive and out of the hospital (DAOH) over 48 weeks, incorporating hospitalizations, emergency room (ER) visits, and death.	48 weeks
Animal Naming Test	Change in cognitive function, measured by the Animal Naming Test (ANT), over 48 weeks.	48 weeks
Patient-reported use and perceived effectiveness of pharmacologic and non-pharmacologic pain management strategies	Change from baseline in patient-reported use and perceived effectiveness of pharmacologic and non-pharmacologic pain management strategies at 52 weeks, assessed using a structured study-specific pain management inventory.	52 weeks
Caregiver burden	Change from baseline in care partner caregiver burden, measured by the 12-item Zarit Burden Interview (ZBI-12), over 48 weeks.	48 weeks

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Patient-Centered Outcomes Research Institute; Johns Hopkins University; Mayo Clinic; University of Miami; Columbia University; University of Michigan; University of California, San Francisco; Vanderbilt University Medical Center

Publications and helpful links

Helpful Links

• Website to be used in study intervention

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: August 14, 2026
• First Submitted That Met QC Criteria: August 25, 2026
• First Posted (Actual): August 28, 2026

Study Record Updates

• Last Update Posted (Actual): August 28, 2026
• Last Update Submitted That Met QC Criteria: August 25, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: hepatology; chronic pain; meditation; interventional; walking; cirrhosis; liver; pain management; cirrhosis pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Neurobehavioral Manifestations; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Chronic Pain; Fibrosis; Agnosia
• Other Study ID Numbers: MP-2025C1-43619

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Dissemination of results from this trial will be conducted in accordance with policies and procedures established by the Executive Committee. All abstracts, presentations, and manuscripts arising from this study will be reported to the Patient-Centered Outcomes Research Institute (PCOR)I in compliance with contractual requirements.

Fundamentally, PCORI's Policy for Data Management and Data Sharing articulates PCORI's expectation that Awardees make data and data documentation (Full Data Package) from their PCORI-funded research projects available to third-party requestors.

The deposition is centered around the Full Data Package, which is comprised of the Analyzable Data Set, Full Protocol, metadata, data dictionary, full statistical analysis plan (including all amendments and all documentation for additional work processes), and analytic code from a PCORI-funded research project.

• IPD Sharing Time Frame: Results submitted to ClinicalTrials.gov or other applicable database: 9/1/2030 Contract term date: 3/31/2032
• IPD Sharing Access Criteria: Results submitted to ClinicalTrials.gov or other applicable database
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No