Online Prehabilitation for Liver Cirrhosis

(OPAL Trial)

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?

Physical frailty is common in patients awaiting liver transplantation and has been associated with poor health outcomes. There is promising data from small studies showing that behavioural, nutrition and exercise therapy (prehabilitation) improves physical function in patients while they are waiting for a liver transplant. The proposed trial will assess if a 12-week online prehabilitation program improves physical function in patients listed for liver transplantation. Over 4 years, 221 patients will be recruited from 5 transplant centres across Canada and will be randomized to receive either the online prehabilitation program or usual care. The primary outcome will be the change in distance walked in 6 minutes between the beginning and end of the study. Secondary and exploratory outcomes include changes in the liver frailty intake, health-related quality of life, covert hepatic encephalopathy, and post-transplant health- related outcomes. Results will be compared between the intervention and usual care groups. If feasible, an economic evaluation will compare the costs and benefits of the prehabilitation program versus usual 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.

Is online prehabilitation safe for people with liver cirrhosis?

Research on prehabilitation, including exercise programs for people with liver cirrhosis, shows it is generally safe and can improve fitness and quality of life without serious side effects. ^{1 2 3 4 5}

How is the Online Prehabilitation Program different from other treatments for liver cirrhosis?

The Online Prehabilitation Program is unique because it offers a digital approach to improving physical fitness and frailty in liver cirrhosis patients, using virtual tools and exercises that can be done at home, making it more accessible and convenient compared to traditional in-person exercise programs. ^{1 2 5 6 7}

What data supports the effectiveness of the treatment Online Prehabilitation Program for liver cirrhosis?

Research shows that prehabilitation, which includes exercise and diet interventions, can improve physical function and potentially enhance survival in patients with advanced liver disease. Additionally, digital prehabilitation programs have been effective in improving health-related quality of life in cancer patients, suggesting potential benefits for liver cirrhosis patients as well. ^{2 4 7 8 9}

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.

Own an internet-connected device

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

Exclusion Criteria

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

I need a transplant due to bile duct cancer.

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

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 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]

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]

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]

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]

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]

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]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Prehabilitation-Driven Changes in Frailty Metrics Predict Mortality in Patients With Advanced Liver Disease. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Home-Based Physical Activity and Diet Intervention to Improve Physical Function in Advanced Liver Disease: A Randomized Pilot Trial. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

An Outpatient Hospital-based Exercise Training Program for Patients With Cirrhotic Liver Disease Awaiting Transplantation: A Feasibility Trial. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Cost Analysis of a Digital Multimodal Cancer Prehabilitation. [2023]

5. Denmark 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. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Physical Effects, Safety and Feasibility of Prehabilitation in Patients Awaiting Orthotopic Liver Transplantation, a Systematic Review. [2022]

7. England 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. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Exercise in cirrhosis: Translating evidence and experience to practice. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

The tele-liver frailty index (TeLeFI): development of a novel frailty tool in patients with cirrhosis via telemedicine. [2023]