LiveSMART Trial to Prevent Falls in Patients With Cirrhosis

University of Michigan230 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

Interventions

Enhanced Usual CareBEHAVIORAL

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 exerciseBEHAVIORAL

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)BEHAVIORAL

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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 Inclusion Criteria for the Caregivers of the participants: * Adult \> 18 years of age * Informal caregiver of a participant enrolled in LIVE-SMART * English speaking Exclusion Criteria for the Caregivers of the participants: \- Non-English speaking

Outcomes

Primary Outcomes

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).