Lactulose + TeleTai-Chi for Liver Cirrhosis

Recruiting at 2 trial locations

Overseen By Samantha Nikirk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Michigan

Must not be taking: Sorafenib, Atezolizumab, Regorafinib, Cabozatinib

Disqualifiers: Overt hepatic encephalopathy, Cancer, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

430 Participants Needed

Trial Summary

What is the purpose of this trial?

This multicenter trial is being conducted to determine if sequential lactulose and Tele (virtual) Tai-Chi reduces the rate of injurious fall, non-injurious falls, incident overt Hepatic Encephalopathy (HE), and death or liver transplant over 24 weeks. Participants that are enrolled will be randomized to stage one of this project for approximately 12 weeks. After completing stage one, participants will be re-randomized to stage 2 of the project that will last approximately 12 more weeks. The study hypothesizes that sequential lactulose/TeleTai-Chi will reduce falls, incident overt HE, death and physical frailty and will improve cognitive function, and Health Related Quality of Life (HRQOL) over 24 weeks compared to other treatment combinations.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, if you are currently taking Sorafenib, Atezolizumab/Bevacizumab, Regorafinib, or Cabozatinib, you cannot participate in the trial.

What data supports the effectiveness of the treatment Lactulose + TeleTai-Chi for Liver Cirrhosis?

Research shows that lactulose, a component of the treatment, is effective in reducing blood ammonia levels and improving mental function in patients with liver cirrhosis, which can help manage hepatic encephalopathy (a brain disorder caused by liver disease). ^{1 2 3 4 5}

What makes the Lactulose + TeleTai-Chi treatment unique for liver cirrhosis?

This treatment is unique because it combines lactulose, a sugar that helps reduce blood ammonia levels, with TeleTai-Chi, a virtual exercise program that may improve overall well-being and immune function, offering a holistic approach to managing liver cirrhosis. ^{1 2 3 4 5}

Research Team

Elliott Tapper, MD

Principal Investigator

University of Michigan

Marina Serper, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for people with liver cirrhosis and signs of portal hypertension, who are willing to exercise and have access to a device with Wi-Fi. They must speak English or Spanish. Excluded are those with recent severe hepatic encephalopathy, high MELD scores (unless stable on dialysis), certain cancer treatments, frequent paracentesis, living in assisted facilities, very high hemoglobin A1C levels, or doing Tai-Chi/vigorous activity already.

Inclusion Criteria

Evidence of portal hypertension meeting specified criteria

I have been diagnosed with cirrhosis through tests or imaging.

Access to Wireless Fidelity (Wi-Fi) at home

Exclusion Criteria

Severe cognitive, vision, or hearing impairment (without use of corrective lenses or hearing assist devices) or psychiatric illness precluding study participation

I am currently undergoing physical therapy.

I have taken lactulose for reasons other than brain liver issues for over 28 days in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1 Treatment

Participants receive lactulose plus enhanced usual care for approximately 12 weeks

12 weeks

Stage 2 Treatment

Participants are re-randomized to receive either TeleTai-Chi or recommended exercise for an additional 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Enhanced Usual Care
• Investigator recommended exercise
• Lactulose
• TeleTai-Chi (virtual)

Trial Overview The LiveSMART Trial tests if lactulose followed by virtual Tai-Chi can reduce falls and improve cognitive function over 24 weeks compared to other treatments in patients with cirrhosis. Participants will be randomly assigned to different treatment combinations for two stages lasting approximately 12 weeks each.

Participant Groups

Group I: Treatment (Lactulose) plus Enhanced Usual Care then recommended exercise Experimental Treatment 3 Interventions

This is considered stage 2 for 12 weeks (for re-randomized participants)

Group II: Treatment (Lactulose) plus Enhanced Usual Care then TeleTai-Chi exercise classes Experimental Treatment 3 Interventions

This is considered stage 2 for 12 weeks (for re-randomized participants)

Group III: Treatment (Lactulose) group plus Enhanced Usual Care Experimental Treatment 2 Interventions

Participants will be in stage 1 for approximately 12 weeks and then be re-randomized for stage 2.

Group IV: Enhanced Usual Care group followed by Tele-Tai Chi exercise classes Experimental Treatment 2 Interventions

This is considered stage 2 for 12 weeks (for re-randomized participants)

Group V: Enhanced Usual Care group followed by investigator recommended exercise Active Control 2 Interventions

This is considered stage 2 for 12 weeks (for re-randomized participants).

Group VI: Enhanced Usual Care group Active Control 1 Intervention

Participants will be in stage 1 for approximately 12 weeks and then be re-randomized for stage 2.

Lactulose is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Lactulose for:

• Hepatic encephalopathy
• Constipation

Approved in European Union as Lactulose for:

• Hepatic encephalopathy
• Constipation

Approved in Canada as Lactulose for:

• Hepatic encephalopathy
• Constipation

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Findings from Research

In a study involving 40 patients with liver cirrhosis and hepatic encephalopathy, both crystalline pure lactulose (Laevolac Cristalli) and lactitol were effective in maintaining treatment for the condition.

Crystalline lactulose had a significantly lower incidence of side effects compared to previous formulations, making it better tolerated and more accepted by patients while maintaining similar efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A clinical comparative study of crystalline pure lactulose and powder pure lactitol in portasystemic encephalopathy of cirrhotic patients]. Grandi, M., Sacchetti, C., Pederzoli, S., et al.[2015]

In a study involving 20 cirrhotic patients, treatment with crystalline lactulose for 30 days significantly reduced blood ammonia levels compared to a control group, indicating its efficacy in managing liver function complications.

Lactulose treatment also appeared to enhance certain immune responses, such as increased CD16 lymphocyte levels and antibacterial activity, suggesting it may help activate the immune system in patients with liver cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crystalline lactulose in the therapy of hepatic cirrhosis. Evaluation of clinical and immunological parameters. Preliminary results. Vendemiale, G., Palasciano, G., Cirelli, F., et al.[2013]

Non-absorbable disaccharides, such as lactulose and lactitol, significantly reduce mortality and improve hepatic encephalopathy symptoms in patients with cirrhosis, based on a systematic review of 38 randomized clinical trials involving 1828 participants.

The use of non-absorbable disaccharides also appears to lower the risk of serious adverse events related to liver disease, indicating their potential as a safe and effective treatment option for hepatic encephalopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis. Gluud, LL., Vilstrup, H., Morgan, MY.[2022]

In a study of 14 cirrhotic patients with portal-systemic shunting but no detectable encephalopathy, lactulose treatment for 15 days significantly improved psychometric test results, indicating potential benefits for subclinical hepatic encephalopathy.

The study found no correlation between biochemical parameters and psychometric performance, suggesting that lactulose may specifically target cognitive dysfunction related to liver issues rather than overall liver function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactulose improves psychometric testing in cirrhotic patients with subclinical encephalopathy. Horsmans, Y., Solbreux, PM., Daenens, C., et al.[2019]

Non-absorbable disaccharides, such as lactulose and lactitol, significantly reduce mortality and improve hepatic encephalopathy symptoms in patients with cirrhosis, based on a systematic review of 38 randomized clinical trials involving 1828 participants.

The use of non-absorbable disaccharides also appears to lower the risk of serious adverse events related to liver disease, indicating their potential as a safe and effective treatment option for hepatic encephalopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis. Gluud, LL., Vilstrup, H., Morgan, MY.[2020]

References

1. Italy pubmed.ncbi.nlm.nih.gov

[A clinical comparative study of crystalline pure lactulose and powder pure lactitol in portasystemic encephalopathy of cirrhotic patients]. [2015]

2. Germany pubmed.ncbi.nlm.nih.gov

Crystalline lactulose in the therapy of hepatic cirrhosis. Evaluation of clinical and immunological parameters. Preliminary results. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Lactulose improves psychometric testing in cirrhotic patients with subclinical encephalopathy. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis. [2020]