NCT05794555

Brief 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. 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
230

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jun 2023

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 20, 2023

Completed
14 days until next milestone

First Posted

Study publicly available on registry

April 3, 2023

Completed
2 months until next milestone

Study Start

First participant enrolled

June 13, 2023

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 7, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 7, 2025

Completed
Last Updated

September 10, 2025

Status Verified

September 1, 2025

Enrollment Period

1.7 years

First QC Date

March 20, 2023

Last Update Submit

September 3, 2025

Conditions

Keywords

Exercise programLactuloseTai-ChiFall preventionDietary Protein

Outcome Measures

Primary Outcomes (1)

  • Number of patients 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).

    Baseline to 24 weeks (following stage 2)

Secondary Outcomes (17)

  • Injurious Falls

    Baseline to 24 weeks (following stage 2)

  • Non-Injurious Falls

    Baseline to 24 weeks (following stage 2)

  • Incident Overt hepatic encephalopathy (HE)

    Baseline to 24 weeks (following stage 2)

  • Death/transplant

    Baseline to 24 weeks (following stage 2)

  • Incident of Liver Transplant

    Baseline to 24 weeks (following stage 2)

  • +12 more secondary outcomes

Study Arms (4)

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

Behavioral: Enhanced Usual CareBehavioral: 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

Behavioral: Enhanced Usual CareDrug: LactuloseBehavioral: 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

Behavioral: Enhanced Usual CareBehavioral: 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

Behavioral: Enhanced Usual CareDrug: LactuloseBehavioral: Investigator recommended exercise

Interventions

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.

Enhanced Usual Care group followed by Tele-Tai Chi exercise classesEnhanced Usual Care group followed by investigator recommended exerciseTreatment (Lactulose) plus Enhanced Usual Care then TeleTai-Chi exercise classesTreatment (Lactulose) plus Enhanced Usual Care then recommended exercise

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.

Treatment (Lactulose) plus Enhanced Usual Care then TeleTai-Chi exercise classesTreatment (Lactulose) plus Enhanced Usual Care then recommended exercise

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.

Enhanced Usual Care group followed by investigator recommended exerciseTreatment (Lactulose) plus Enhanced Usual Care then recommended exercise

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.

Enhanced Usual Care group followed by Tele-Tai Chi exercise classesTreatment (Lactulose) plus Enhanced Usual Care then TeleTai-Chi exercise classes

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)
  • 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

You may not qualify if:

  • 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
  • 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
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor Scott & White Research Institute (BSW)

Dallas, Texas, 75246, United States

Location

MeSH Terms

Conditions

Liver CirrhosisHypertension, Portal

Interventions

Lactulose

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesFibrosisPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

DisaccharidesOligosaccharidesPolysaccharidesCarbohydratesSugars

Study Officials

  • Elliott Tapper, MD

    University of Michigan

    PRINCIPAL INVESTIGATOR
  • Marina Serper, MD, MS

    University of Pennsylvania

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor of Internal Medicine

Study Record Dates

First Submitted

March 20, 2023

First Posted

April 3, 2023

Study Start

June 13, 2023

Primary Completion

March 7, 2025

Study Completion

March 7, 2025

Last Updated

September 10, 2025

Record last verified: 2025-09

Locations