LiveSMART Trial to Prevent Falls in Patients With Cirrhosis

Portal Hypertension Clinical Trial

Official title:

LiveSMART: A Sequential, Multiple Assignment Randomized Trial to Prevent Falls in Patients With Cirrhosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05794555
• Other study ID #: HUM00225275
• Secondary ID: CER-2021C3-24907
• Status: Recruiting
• Phase: Phase 3
• Start date: June 13, 2023
• Est. completion date: September 2025

Study information

• Verified date: June 2024
• Source: University of Michigan
• Contact: Samantha Nikirk
• Phone: 734-232-4182
• Email: samjwalk[@]med.umich.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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. The caregivers that are enrolled are not in the clinical trial. Because all of the outcome measures in the supplemental study are other outcome measures (neither primary nor secondary to the trial) these are not included in this registration.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 430
• Est. completion date: September 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cirrhosis, Liver
• Fibrosis
• Hypertension, Portal
• Liver Cirrhosis
• Portal Hypertension

Intervention

Behavioral:
• Enhanced Usual Care
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.

Drug:
• Lactulose
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.

Behavioral:
• Investigator 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.
• TeleTai-Chi (virtual)
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.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Baylor Scott & White Research Institute (BSW)	Dallas	Texas
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	Patient-Centered Outcomes Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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 stated (higher is better).	Baseline to 24 weeks (following stage 2)
Secondary	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 will be queried and data will also be abstracted from the Electronic Medical Record (EMR).	Baseline to 24 weeks (following stage 2)
Secondary	Injurious Falls	Falls include: Fracture, dislocation, cut, head injury, soft - tissue injury requiring hospitalization.	Baseline to 24 weeks (following stage 2)
Secondary	Non-Injurious Falls	Non- Injurious Falls include: Inadvertently coming to rest on the floor or lower level	Baseline to 24 weeks (following stage 2)
Secondary	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.	Baseline to 24 weeks (following stage 2)
Secondary	Death/transplant	Mortality with any cause or liver transplantation	Baseline to 24 weeks (following stage 2)
Secondary	Incident of Liver Transplant	Replacement of a diseased liver with the healthy liver from another person.	Baseline to 24 weeks (following stage 2)
Secondary	Visual Analog Scale (VAS)	This is 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.	Baseline to 24 weeks (following stage 2)
Secondary	The Patient Reported Outcome Measurement Information System (PROMIS)-29+2 v2.1	There are seven health domains including physical function, anxiety, depression, fatigue, sleep disturbances, ability to participate in social roles and activities, and pain interference. Each category consists of 4 questions. Questions are ranked on a 5-point Likert scale, with higher scores at times indicating better quality of life, and at other times indicating poorer quality of life. There is a pain rating scale ranging from 0 to 10, with higher scores indicating higher pain level.	Baseline to 24 weeks (following stage 2)
Secondary	Depression based on The Patient Reported Outcome Measurement Information System (PROMIS)-29+2 v2.1	There are 4 questions that participants complete regarding depression (never 1 - always 5). Scoring ranges (4-20) with higher scores indicating more depression.	Baseline to 24 weeks (following stage 2)
Secondary	Sleep quality based on the PROMIS-29+2 v2.1	There are 4 questions and are ranked on a 5-point Likert scale (not at all or very poor 1 - 5 very much). Scoring ranges (4-20) with lower scores indicating better sleep quality.	Baseline to 24 weeks (following stage 2)
Secondary	Physical frailty based on the Liver Frailty Index	Physical frailty will be assessed with this index and is a composite of handgrip, timed chair-stands, and balance. The index ranges from -1.26 (robust) to 6.9 (frail), 50th percentile is 3.9. For individuals enrolled remotely, the study team will assess chair-stands.	Baseline to 24 weeks (following stage 2)
Secondary	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	Baseline to 24 weeks (following stage 2)
Secondary	Intervention Fidelity	Evaluation of intervention fidelity will be assessed at 50% and 100% of study completion as percent delivery of key intervention components including coordinator trainings, lactulose prescriptions ordered, enhanced usual care components delivered, Short Message Service (SMS) assessments sent, study visits completed, and exercise sessions completed.	12 and 24 weeks
Secondary	Participant adherence	Adherence to lactulose, Tai-Chi, and nighttime protein supplementation will be monitored. Adherence is the proportion of expected-to-actual treatment days completed during the intervention.	12 weeks and 24 weeks
Secondary	Participant satisfaction with the trial and interventions based on the Patient Global Impression of Change (PGIC)	Satisfaction with the trial will be assessed using the 6-item Patient Global Impression of Change (PGIC). Participants select from Very much improved 1 - Very much worse 7. Lower scores indicate higher satisfaction.	12 weeks and 24 weeks
Secondary	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 range 8-40, with a lower score meaning higher function.	12 weeks and 24 weeks