Cirrhosis, LiverPhase 3NCT05794555
LiveSMART Trial to Prevent Falls in Patients With Cirrhosis
A Phase 3 study testing Lactulose, Investigator recommended exercise and TeleTai-Chi (virtual) in people with Cirrhosis, Liver and Portal Hypertension, run by University of Michigan at 3 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cirrhosis, Liver, Portal Hypertension
- What is being tested?
- Lactulose, Investigator recommended exercise and TeleTai-Chi (virtual)
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 233 participants
- Where
- 3 sitesUnited States
- Study dates
- 13 Jun 2023to 7 Mar 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of cirrhosis based on histology and/or imaging specified in the protocol.
- Evidence of portal hypertension - must meet at least one of the following criteria:
- Ascites (present or within past 2 years)
- Varices (seen by Esophagogastroduodenoscopy or by Ultrasound(US) or cross-sectional imaging)
- Fibroscan Liver stiffness measurement (LSM) >25 kilopascals (kPa) (if no other factors present)
- Magnetic resonance elastography (MRE) LSM > 5 kPa (if no other factors present)
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- Acoustic radiation force impulse LSM > 17kpa (if no other factors present)
- Hepatic vein pressure gradient > 10 millimetres of mercury (mmHg)
- Portal hypertensive gastropathy seen on Esophagogastroduodenoscopy
- Platelet count < 80/ units per liter (uL)
- Recanalized umbilical vein (by US or cross-sectional imaging)
- Access to Wireless Fidelity (Wi-Fi) at home
- Owns or access to a smartphone, tablet or computer
- English or Spanish speaking
- Willing to participate in exercise program
- Adult > 18 years of age
- Informal caregiver of a participant enrolled in LIVE-SMART
- English speaking
Who cannot join
- Overt hepatic encephalopathy (HE) within 6 months, requiring >28 days total of lactulose
- Took lactulose for non - HE reasons for >28 days total in last 6 months
- Took Rifaximin for > 28 days total in last 6 months
- Model for End Stage Liver Disease (MELD) > 25 (Exception: MELD > 25 with clinically stable End-Stage Renal Disease (ESRD) for whom the bilirubin is < 5 g/dL)
- Barcelona Clinic Liver Cancer (BCLC) > C Hepatocellular Carcinoma (HCC)
- Currently taking Sorafenib, Atezolizumab/Bevacizumab, Regorafinib, or Cabozatinib
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- Greater than (>) 3 paracentesis/month in last 2 months
- Active Metastatic solid malignancy or acute leukemia within last 3 years
- Severe cognitive, vision, or hearing impairment (without use of corrective lenses or hearing assist devices) or psychiatric illness precluding study participation
- Currently participates in Tai-Chi or performs >150 min/week vigorous physical activity
- Currently receiving lower body physical and/or occupational therapy
- Living in an assisted living facility
- Hemoglobin A1C > 12 (within past 12 months)
- Requires a low galactose diet
- Deemed unsuitable by the study investigator
- Non-English speaking
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Michigan
Ann Arbor, Michigan, 48109
Baylor Scott & White Research Institute (BSW)
Dallas, Texas, 75246
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: LiveSMART: A Sequential, Multiple Assignment Randomized Trial to Prevent Falls in Patients With Cirrhosis
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.
Read more
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.
As detailed below, an observational component that enrolls caregivers of the trial participants is being conducted. Upon completion, Participants listed in the record here only include trial participants; and the observational component was moved to a new registration for clarity, NCT07140120.
Read the detailed description
The Clinicaltrials.gov registration record was updated as requested by Patient-Centered Outcomes Research Institute (PCORI) based on protocol amendment version 3.0 after approval by the Institutional Review Board. These changes included: the additional aim for a supplemental observational study to assess social determinants of health, financial burdens, etc., and includes recruitment of the caregivers for this supplemental study along with the trial participants, as well as updated outcomes for the trial. After further discussion with PCORI, these changes were removed from this record and used to create a separate record for the supplemental study focused on caregivers (NCT07140120).
The caregivers that are enrolled are not in the clinical trial. All clinical trial information is provided in this record, but upon completion of enrollment and consideration of transparent results reporting, it was decided to move all the items related to the observational supplemental study to its own record.
To improve clarity in the record, the two arms representing stage 1 of the project were incorporated into the remaining four representing stage 2, so the remaining arms now represent both stage 1 and stage 2.
- Conditions
- Cirrhosis, Liver, Portal Hypertension
- Being tested
- Enhanced Usual Care, Lactulose, Investigator recommended exercise, TeleTai-Chi (virtual)
- Keywords
- Exercise program, Lactulose, Tai-Chi, Fall prevention, Dietary Protein
- Medical subject headings
- Liver Cirrhosis, Hypertension, Portal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enhanced Usual CareBehavioural
Patients will be provided and counseled on two methods which will enhance care. The first is a handout on nutrition recommendations and protein supplementation. This will include the recommendation of both high protein snacks during the daytime (e.g., protein bars) and a high-protein night-time snack (e.g., peanut butter and crackers). The second will be to counsel participants on falls prevention methods that can be enacted in day-to-day life. All participants will be provided with a standard hand-out of Centers for Disease Control and Prevention (CDC)-endorsed fall-risk reduction measures.
LactuloseDrug
Patients will be prescribed lactulose and will also receive enhanced usual care. Lactulose will be taken on a specific schedule based on the average number of bowel movements on average per day. It will be started at 15 milliliter (mL) dose and will be instructed to slowly increase the lactulose dose over the course of the first week of Stage 1 participation. The prescribed maximum dose will be 30 mL (20g) twice daily. The dose will slowly increase toward the maximum or until participants reach 2-3 soft bowel movements daily.
Participants that receive Lactulose during stage 1 will continue this in stage 2.
Investigator recommended exerciseBehavioural
Participants randomized to enhanced usual care will be reminded of standard fall precautions outlined in the Fall Prevention Primer that were provided in Stage 1 and will receive exercise recommendations.
TeleTai-Chi (virtual)Behavioural
TeleTai-Chi will be taught remotely via live Zoom classes of up to 15 patients by a certified TeleTai-Chi instructor three times per week (for approximately 12 weeks). Classes will be conducted via a HIPAA-compliant Zoom server through the University of Michigan. Participants will be instructed to use Zoom by smartphone, tablet, or computer. High-Definition Multimedia Interface (HDMI) cables and other device specific equipment to connect devices to televisions will be provided.
| Study group | Role | What they receive |
|---|---|---|
| Enhanced Usual Care group followed by investigator recommended exercise | Active comparator | Enhanced Usual Care (EUC) at Stage 1 (12 weeks) and then re-randomization to EUC then Investigator-Recommended Exercise at Stage 2 Receives: Behavioral: Enhanced Usual Care; Behavioral: Investigator recommended exercise |
| Treatment (Lactulose) plus Enhanced Usual Care then TeleTai-Chi exercise classes | Experimental | 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 Receives: Behavioral: Enhanced Usual Care; Drug: Lactulose; Behavioral: TeleTai-Chi (virtual) |
| Enhanced Usual Care group followed by Tele-Tai Chi exercise classes | Experimental | Enhanced Usual Care (EUC) at Stage 1 (12 weeks) and then re-randomization to EUC then Tele-Tai Chi exercise classes at Stage 2 Receives: Behavioral: Enhanced Usual Care; Behavioral: TeleTai-Chi (virtual) |
| Treatment (Lactulose) plus Enhanced Usual Care then recommended exercise | Experimental | 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 Receives: Behavioral: Enhanced Usual Care; Drug: Lactulose; Behavioral: Investigator recommended exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing a Hierarchical Composite of Events Over 24 Weeks: Injurious Falls, Non-injurious Falls, Incident Hepatic Encephalopathy, Liver Transplant, and Death/Transplant
Composite outcome is defined as any of the following:
- Injurious Fall: Fracture, dislocation, cut, head injury, soft - tissue injury requiring medical intervention including: Hospitalization or overnight observation in the Emergency Room (ER); surgery, transfusion, stitches
- Non - Injurious Fall: Inadvertently coming to rest on the floor or lower level
- Include falls that result in minor injuries that are addressed with first aid (e.g., ice, bandage)
- Incident Overt HE: Acute disorientation requiring hospitalization or the initiation of HE - directed therapy, confirmed by a gastroenterologist or study investigator
- Death: Mortality with any cause
- Liver transplant: Replacement of a diseased liver with the healthy liver from another person because of acute-on-chronic liver failure (using the EASL-CLIF-C definition consisting of an acute increase in the bilirubin and/or INR, acute kidney injury, overt HE, hypertension, and hypoxia).
Measured: Baseline to 24 weeks
Secondary outcomes (17)
Injurious Falls
Results reflect the number of participants who experienced at least one injurious fall. Injurious falls include: Fracture, dislocation, cut, head injury, soft - tissue injury requiring hospitalization.
Measured: Baseline to 24 weeks
Non-Injurious Falls
Results reflect the number of participants who experienced at least one non-injurious fall. Non- injurious falls include: Inadvertently coming to rest on the floor or lower level.
Measured: Baseline to 24 weeks
Incident Overt Hepatic Encephalopathy (HE)
Incident Overt HE includes: Acute disorientation requiring hospitalization or the initiation of HE - directed therapy, confirmed by a gastroenterologist or study investigator.
Measured: Baseline to 24 weeks
Death/Transplant for Acute-on-Chronic Liver Failure (ACLF)
Results reflect participants who died, or who received a liver transplant because of ACLF.
Measured: Baseline to 24 weeks
Incident of Liver Transplant for Non-ACLF Reason
Results reflect the number of participants who received replacement of a diseased liver with the healthy liver from another person for any reason other than ACLF.
Measured: Baseline to 24 weeks
Days-alive and Out-of-the-hospital
Days-alive and out-of-the-hospital is a continuous value, 1 for each day alive, 0 for days in hospital. Participants were queried and data was also abstracted from the Electronic Medical Record (EMR). Results reflect the average number of days participants were alive and out of the hospital.
Measured: Approximately 26 Weeks
Change in Cognitive Function Based on the Animal Naming Test (ANT)
The animal naming test assesses cognitive function. It is a timed test that that consists of participants listing as many unique animals as possible in 60 seconds. This is a validated test used for the assessment of hepatic encephalopathy. The score is the number of unique animals named (higher is better). Results reflect change from baseline.
Measured: Baseline to 24 weeks
Change in Visual Analog Scale (VAS)
This was a 1-item global rating of health scored 0-100. A score of 100 means the best health and 0 means the worst health imagined. Results reflect change from baseline.
Measured: Baseline to 24 weeks
Change in The Patient Reported Outcome Measurement Information System (PROMIS)-29+2 v2.1 Profile (PROPr)
PROPr is the combined score of the two scales in the PROMIS 29+2, a quality-of-life scale and a pain-rating scale, and is used to calculate a preference score. The scores from both scales provide an overall summary of health-related quality of life based on multiple domains summarizing a metric ranging from 0 (as bad as dead) to 1 (perfect or ideal health). Results reflect change from baseline.
Measured: Baseline to 24 weeks
Change in Depression Based on The Patient Reported Outcome Measurement Information System (PROMIS)-29+2 v2.1
There were 4 questions that participants completed regarding depression. The scores were converted to t scores, which were normalized from the raw scores. The t score ranged from 0-100 with 0 denoting worst depression and 100 indicating no depression. Results reflect the change from baseline.
Measured: Baseline to 24 weeks
Change in Sleep Quality Based on the PROMIS-29+2 v2.1
There were 4 questions that participants completed regarding sleep quality. The scores were converted to t scores, which were normalized from the raw scores. The t score ranged from 0-100 with 0 denoting worst sleep quality and 100 indicating best sleep quality. Results reflect change from baseline.
Measured: Baseline to 24 weeks
Physical Frailty Based on the Liver Frailty Index
Physical frailty was assessed with this index and was a composite of handgrip, timed chair-stands, and balance. The index ranged from -1.26 (robust) to 6.9 (frail), 50th percentile is 3.9. For individuals enrolled remotely, the study team assessed chair-stands.
Measured: Baseline to 24 weeks
Change in Physical Frailty Based on the Activities of Daily Living (ADLs)
Activities of daily living (ADLs), is a validated self-reported measure (disability is defined as >1 ADL deficit) recommended by the American Society for Transplantation and AASLD. The score ranged from 0 to 6 (6 indicating full independence, 4 moderate impairment, and 2 or less severe functional impairment). Results reflect change from baseline.
Measured: Baseline to 24 weeks
Intervention Fidelity
Evaluation of intervention fidelity was assessed at 50% and 100% of study completion. Results reflect participants who maintained fidelity by completing at least one of the following key intervention components: coordinator trainings, lactulose prescriptions ordered, enhanced usual care components delivered, Short Message Service (SMS) assessments sent, study visits completed, or exercise sessions completed.
Measured: 24 weeks
Participant Adherence
Adherence to lactulose, Tai-Chi, and nighttime protein supplementation was monitored. Results reflect the number of participants who discontinued their assigned intervention.
Measured: 24 weeks
Participant Satisfaction With the Trial and Interventions Based on the Patient Global Impression of Change (PGIC)
Satisfaction with the trial was assessed using the 6-item Patient Global Impression of Change (PGIC). Participants selected from 1 (very much improved) to 7 (very much worse). Lower scores indicated higher satisfaction.
Measured: 12 weeks and 24 weeks
Change in Short Form (SF) - 8
The SF-8 is an abbreviated 8-item version of an original 36-item health survey (SF-36). It is a generic multipurpose quality of life instrument. It contains psychometrically based physical and mental health summary measures. The eight domains include general health, physical functioning, role physical, bodily pain, vitality, social functioning, mental health and role emotional. The scores were converted to t scores, which were normalized from the raw scores. The t score ranged from 0-100 with 0 denoting worst quality of life and 100 indicating best quality of life. Results reflect change from baseline.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2023
- Study start13 Jun 2023
- Primary completion7 Mar 2025
- Study completion7 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cirrhosis, LiverStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Participants will be randomized in stage 1 to enhanced usual care or enhanced usual care plus lactulose. After 12 weeks participants will be re-randomized to TeleTai-Chi (at-home, via Zoom, supervised by a study team instructor) vs. continued enhanced usual care. The participants that took lactulose in Stage 1 will continue to take lactulose through Stage 2 until their participation is complete. The caregivers (of the trial participants) involved in the observational sub-study are not included in the trial in any fashion.
- Masking
- None (open label)
- Enrolment
- 233 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute
- Responsible party
- Principal investigator, Elliot B. Tapper, University of Michigan
- Investigators
- Elliott Tapper, MD, Principal investigator, University of MichiganMarina Serper, MD, MS, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05794555
- Sponsor's protocol ID
- HUM00225275
- Other IDs
- CER-2021C3-24907
- Status last verified
- May 2026
- First submitted
- 20 Mar 2023
- Last updated
- 31 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD will be deposited in a repository.