Lactulose + TeleTai-Chi for Liver Cirrhosis

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether lactulose (a sugar used to treat constipation and liver problems) and virtual Tai-Chi can aid individuals with liver cirrhosis by reducing falls, improving brain function, and enhancing quality of life over 24 weeks. Participants will be divided into groups to test different combinations of these treatments. Suitable candidates have cirrhosis (liver scarring) and signs of high blood pressure in the liver, such as fluid buildup or visible veins, and are willing to participate in an exercise program using a device with internet access. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that lactulose is often used to treat liver disease, particularly to prevent brain-related issues like hepatic encephalopathy. It can improve quality of life and increase survival rates. However, it may cause side effects, such as digestive problems or changes in body fluids and electrolytes, which are crucial for the body's functions.

Regarding TeleTai-Chi, studies suggest it is generally safe and may help improve outcomes, such as reducing falls in people with liver problems. Tai Chi, a gentle exercise that can be done at home, has shown benefits for various health conditions.

Overall, both treatments are under study for safety and effectiveness, with previous research providing a solid foundation. The trial's late stage indicates that the treatments have already shown promise in earlier tests. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Lactulose and TeleTai-Chi for treating liver cirrhosis because it uniquely blends a well-established treatment with an innovative approach. Lactulose is already known for its ability to help reduce ammonia in the blood, which is crucial for patients with liver cirrhosis. What makes this trial stand out is the addition of TeleTai-Chi, a virtual exercise program that can be accessed from home, offering an easy and accessible way for patients to incorporate physical activity into their routine. This combination not only aims to manage symptoms but also potentially enhances patient quality of life through convenient and holistic care. By integrating movement and medication, the trial seeks to address both physical and mental well-being, opening new doors in liver cirrhosis management.

What evidence suggests that this trial's treatments could be effective for liver cirrhosis?

Research has shown that lactulose, which participants in this trial may receive, benefits people with liver cirrhosis. It can prevent a brain disorder related to liver disease, aid recovery, and improve survival chances. Studies also indicate that lactulose can enhance quality of life and reduce death rates in those with severe liver-related brain issues.

Regarding TeleTai-Chi, another treatment option in this trial, research suggests it might help prevent falls, which are common and risky for people with cirrhosis. Tai Chi involves gentle exercises and stretching, which can improve balance and flexibility. While more research is needed on practicing Tai Chi online, it is believed to boost physical stability and health-related quality of life. ^{1 6 7 8 9}

Who Is on the Research Team?

Elliott Tapper, MD

Principal Investigator

University of Michigan

Marina Serper, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Lactulose plus Enhanced Usual Care (EUC) at Stage 1 (12 weeks) and then re-randomization to Lactulose plus EUC then Investigator-Recommended Exercise at Stage 2

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

Lactulose plus Enhanced Usual Care (EUC) at Stage 1 (12 weeks) and then re-randomization to Lactulose plus EUC then TeleTai-Chi exercise classes at Stage 2

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

Enhanced Usual Care (EUC) at Stage 1 (12 weeks) and then re-randomization to EUC then Tele-Tai Chi exercise classes at Stage 2

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

Enhanced Usual Care (EUC) at Stage 1 (12 weeks) and then re-randomization to EUC then Investigator-Recommended Exercise at 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+

Published Research Related to This Trial

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10578757/

Lactulose in cirrhosis: Current understanding of efficacy, ... Lactulose reverses minimal HE, prevents overt HE, improves quality of life, increases the rate of recovery from overt HE, and improves survival rates.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6416096/

Long-term management of hepatic encephalopathy with ... These studies showed that lactulose is effective for the prevention of overt HE recurrence over the long term and that the addition of rifaximin to lactulose ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05788627

Effectiveness of Oral Lactulose Versus Lactulose Enema in ... It can be increased as tolerated. At least, 2-4 loose stools per day should be passed by the patient. Lactulose is also effective as primary prophylaxis ...

4. journals.lww.com journals.lww.com/hepcomm/fulltext/2023/11010/lactulose_in_cirrhosis__current_understanding_of.6.aspx

Lactulose in cirrhosis: Current understanding of efficacy,... Lactulose also reduced mortality to 8.5% in patients with cirrhosis and overt HE versus 14% among those with overt HE not taking lactulose.

5. link.springer.com link.springer.com/article/10.1007/s11011-025-01533-w

Lactulose use among patients with alcohol-related liver ... Lactulose is used by 10–20% of patients with ALD cirrhosis, primarily those with severe cirrhosis, and lactulose users have a markedly higher mortality than ...

6. journals.lww.com journals.lww.com/ccmjournal/fulltext/2022/01001/886__safety_of_lactulose_for_the_treatment_of.852.aspx

886: safety of lactulose for the treatment of hepatic ... Lactulose poses several risks to critically ill patients, including ileus formation, metabolic and electrolyte derangements, and hypovolemia. Thus, this ...

7. webmd.com webmd.com/drugs/2/drug-3367-7202/lactulose-oral/lactulose-liver-oral-rectal/details

Lactulose (Constulose, Enulose, and others) - Uses, Side ... Lactulose is used to treat constipation and to prevent and treat a brain condition that can happen in people with liver disease (hepatic encephalopathy).

8. aasld.org aasld.org/liver-fellow-network/core-series/why-series/why-do-we-use-lactulose-and-rifaximin-hepatic

Why do we use Lactulose and Rifaximin for Hepatic ... Lactulose and Rifaximin (Xifaxan) are standards of care for the prevention of overt hepatic encephalopathy in patients with cirrhosis.

9. medcentral.com medcentral.com/drugs/monograph/3367-382338/lactulose-oral

Lactulose: uses, dosing, warnings, adverse events, ... Lactulose therapy is not effective in the treatment of coma associated with infectious hepatitis or other acute disorders of the liver. In a case of ...