Online Prehabilitation for Liver Cirrhosis

(OPAL Trial)

Recruiting at 5 trial locations

Overseen By Margaret McNeely

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alberta

Disqualifiers: Living donor, Robust frailty, Others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

177 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a 12-week online program, the Online Prehabilitation Program, can improve physical function for individuals awaiting a liver transplant. The program includes exercises, nutrition tips, and behavioral support to determine if these elements enhance health outcomes compared to usual care. Participants will be divided into two groups: one using the online program and the other receiving standard resources. The study seeks individuals with liver cirrhosis who are on a transplant list or likely to be listed soon and who exhibit some level of frailty as defined by specific health checks. Participants should be comfortable using an internet-connected device and proficient in English or French. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance pre-transplant care.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this online prehabilitation program is safe for patients with liver cirrhosis?

Research has shown that online prehabilitation programs for people with liver cirrhosis are generally safe. These programs, which include exercise and nutrition advice, can improve fitness and quality of life without causing harm. One study found that participants who followed a structured prehabilitation program experienced improvements in their physical abilities and overall health. There were no major reports of negative effects, indicating that these programs are well-tolerated. For those considering joining a trial, this evidence suggests the treatment is likely safe based on past research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the online prehabilitation program for liver cirrhosis because it offers a comprehensive, digital approach to patient care. Unlike standard treatments that patients typically receive, this program combines acceptance and commitment therapy-based education, nutrition intervention, and exercise intervention, all accessible from a web platform. This method aims to empower patients to actively engage in their care from home, potentially improving their physical and mental health in a more holistic and personalized manner. By integrating these components online, it could enhance accessibility and adherence, offering a promising alternative or complement to traditional in-person therapies.

What evidence suggests that the online prehabilitation program is effective for improving physical function in patients with liver cirrhosis?

Research has shown that a prehabilitation program can improve physical abilities in patients with liver cirrhosis awaiting a transplant. In this trial, participants in the Prehabilitation Group will access an online digital platform featuring exercise, nutrition, and therapy interventions. Studies have found that such programs can boost fitness and reduce weakness. Early results suggest that this type of program is safe and feasible for patients with cirrhosis. Specifically, one study found that patients who participated in a prehabilitation program performed better physically than those who did not. Thus, joining such a program could help patients become stronger and better prepared for a liver transplant. ^{1 2 3 4 6}

Who Is on the Research Team?

Puneeta Tandon, MD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

This trial is for adults over 18 with liver cirrhosis who are somewhat frail or very frail, likely to be listed for a liver transplant, and can speak English or French. They must have internet access and an online device. It's not for those robust in health, expecting a living donor transplant soon, with high MELD-Na scores (>26), unable to consent, with less than 6 months to live, unsafe conditions for virtual participation or specific medical exclusions.

Inclusion Criteria

I am over 18 and have been diagnosed with cirrhosis.

Listed or being worked up with a high likelihood to be listed for LT

Own an internet-connected device

Exclusion Criteria

I need a transplant due to bile duct cancer.

I have had a recent variceal bleed or have varices without proper prevention.

Listed for living related donor transplantation with expected time on the wait list <12 weeks, or model for end-stage liver disease (MELD-Na) Score >26 (Justification: time to transplant is very short)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Prehabilitation

Participants undergo a 12-week online prehabilitation program including nutrition, exercise, and acceptance and commitment therapy

12 weeks

Weekly virtual sessions

Extended Follow-up

Participants have extended follow-up with virtual testing every 12 weeks, up to 6 months after completion of the 12-week trial

6 months

Virtual visits every 12 weeks

Post-Transplant Follow-up

In the subgroup of patients who undergo liver transplantation, in-person and virtual testing will be carried out at approximately 6-12 weeks post-transplant

6-12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Online Prehabilitation Program

Trial Overview The study tests if a 12-week online program focused on behavior, nutrition, and exercise (prehabilitation) can improve physical function in patients waiting for liver transplants compared to usual care. Over four years at five Canadian centers, participants will be randomly assigned to the prehabilitation group or usual care group.

How Is the Trial Designed?

Group I: Prehabilitation Group Experimental Treatment 1 Intervention

The prehabilitation group will be provided with access to the online digital web platform which contains the weekly acceptance and commitment therapy based education videos, nutrition intervention, and exercise intervention.

Group II: Usual Care Active Control 1 Intervention

This group will receive standard care for LT candidates with cirrhosis and will be provided with standard online exercise, nutrition, and behavioural resources. Control participants will not receive access to the online digital platform.

Online Prehabilitation Program is already approved in Canada, United Kingdom for the following indications:

Approved in Canada as Prehabilitation Program for:

• Improving physical function in patients awaiting liver transplantation

Approved in United Kingdom as Digital Prehabilitation for:

• Improving health-related quality of life in patients awaiting liver transplantation

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Published Research Related to This Trial

Prehabilitation programs for patients awaiting orthotopic liver transplantation (OLT) significantly improve physical fitness measures such as VO2 peak, walking distance, and hand grip strength, indicating enhanced aerobic capacity and quality of life.

The review included 1,094 patients and found that prehabilitation is generally safe, with no serious adverse events reported, although adherence rates varied and larger trials are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical Effects, Safety and Feasibility of Prehabilitation in Patients Awaiting Orthotopic Liver Transplantation, a Systematic Review. Jetten, WD., Hogenbirk, RNM., Van Meeteren, NLU., et al.[2022]

Exercise training is highly beneficial for patients with cirrhosis, leading to significant improvements in muscle health, quality of life, and functional capacity, without any reported adverse events.

The authors advocate for routine exercise prescriptions in cirrhosis care, providing clinicians with practical tools and resources to implement exercise programs effectively in various healthcare settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise in cirrhosis: Translating evidence and experience to practice. Tandon, P., Ismond, KP., Riess, K., et al.[2019]

Prehabilitation programs involving exercise training before liver transplantation may improve short-term functional outcomes, with studies showing positive effects on aerobic capacity and muscle strength, although evidence is limited and underpowered.

The only observational study assessing postoperative outcomes suggested a non-significant trend towards reduced readmission rates and shorter hospital stays for patients who underwent prehabilitation, indicating potential benefits without significant harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of prehabilitation on short-term outcomes after liver transplantation: A review of the literature and expert panel recommendations. Vinaixa, C., Martínez Palli, G., Milliken, D., et al.[2023]

A study involving 517 liver transplant candidates showed that a novel prehabilitation strategy significantly improved frailty metrics, particularly in patients who adhered to the program, indicating its potential effectiveness in enhancing patient outcomes.

Improvement in frailty, as measured by the liver frailty index, was linked to better survival rates, with higher compliance to physical therapy visits correlating with a reduced risk of mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prehabilitation-Driven Changes in Frailty Metrics Predict Mortality in Patients With Advanced Liver Disease. Lin, FP., Visina, JM., Bloomer, PM., et al.[2021]

A new telemedicine-enabled frailty assessment tool, the tele-liver frailty index, was developed for adults with cirrhosis, allowing for virtual evaluation of frailty using validated surveys and physical tests.

The tool demonstrated strong predictive ability for identifying frailty in liver transplant patients, with high accuracy (C-statistics of 0.76-0.79), suggesting it can effectively determine which patients need more intensive follow-up or interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The tele-liver frailty index (TeLeFI): development of a novel frailty tool in patients with cirrhosis via telemedicine. Wang, M., Shui, AM., Barry, F., et al.[2023]

A home-based physical activity program (HB-PAP) significantly increased daily step counts and reduced sedentary behavior in patients with cirrhosis over a 12-week period, indicating improved physical activity levels.

The HB-PAP led to notable improvements in aerobic fitness as measured by the six-minute walk test (6MWT), while no significant changes were observed in cardiopulmonary exercise testing (CPET), suggesting that the program effectively supports physical performance in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Home-Based Physical Activity and Diet Intervention to Improve Physical Function in Advanced Liver Disease: A Randomized Pilot Trial. Chen, HW., Ferrando, A., White, MG., et al.[2021]

A 6-week supervised exercise program for patients with cirrhotic liver disease awaiting liver transplantation was feasible, with 56% of participants completing it, indicating that such prehabilitation can be implemented effectively.

Participants in the exercise group showed a significant improvement in peak oxygen consumption (VO2peak), increasing from 16.2 to 18.5 mL/kg/min, while the control group experienced a decline, suggesting that exercise can enhance cardiopulmonary fitness before major surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Outpatient Hospital-based Exercise Training Program for Patients With Cirrhotic Liver Disease Awaiting Transplantation: A Feasibility Trial. Morkane, CM., Kearney, O., Bruce, DA., et al.[2021]

A digital multimodal prehabilitation program for cancer patients significantly improved health-related quality of life (HRQoL), with scores increasing from 69.53 to 85.71 after the program, representing a 23% improvement.

The study, which included 192 participants, suggests that even limited engagement in prehabilitation can enhance quality-adjusted life years (QALYs), indicating both health benefits for patients and potential cost savings for healthcare systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost Analysis of a Digital Multimodal Cancer Prehabilitation. Gkaintatzi, E., Nikolaou, CK., Rampal, T., et al.[2023]

A bimodal tele-prehabilitation program for high-risk colorectal cancer patients showed high feasibility, with an 81% participation rate and a 100% retention rate, indicating that patients were able to complete the program without any adverse events.

Participants demonstrated significant improvements in physical fitness, as evidenced by an increase in the number of repetitions on the 30-second chair-stand test, suggesting that tele-prehabilitation may enhance preoperative fitness, although further research is needed to confirm its overall effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of a tele-prehabilitation program in high-risk patients with colon or rectal cancer undergoing elective surgery: a feasibility study. Franssen, RFW., Bongers, BC., Vogelaar, FJ., et al.[2022]

Citations

1. withpower.com withpower.com/trial/phase-liver-cirrhosis-5-2023-d3221

Online Prehabilitation for Liver Cirrhosis (OPAL Trial) The Online Prehabilitation Program is unique because it offers a digital approach to improving physical fitness and frailty in liver cirrhosis patients, using ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05899231

Online Prehabilitation for Patients Awaiting Liver ... The disease-specific Chronic Liver Disease Questionnaire (CLDQ) is validated in cirrhosis. Overall CLDQ scores calculated for each domain range from 1 (most ...

3. gut.bmj.com gut.bmj.com/content/74/Suppl_4/A10.2

O14 Home-based, virtually delivered prehabalitation for ... An outpatient hospital-based exercise training program for patients with cirrhotic liver disease awaiting transplantation: a feasibility trial. Transplantation.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11202729/

Prehabilitation in patients with cirrhosis awaiting liver ... The feasibility, safety and effectiveness of a multimodal prehabilitation programme in patients with cirrhosis awaiting liver transplantation is ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0955470X24000181

Prehabilitation in patients awaiting liver transplantation Although preliminary evidence suggests that exercise training is safe in patients with cirrhosis, it is unclear if this is the case in patients active on the LT ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05237583

Prehabilitation for Patients Awaiting Liver Transplantation This study will assess the feasibility, safety and effectiveness of a structured prehabilitation program combining exercise training, nutritional optimization ...