LiveSMART Trial to Prevent Falls in Patients With Cirrhosis

Sponsor

University of Michigan (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05794555

Collaborator

Patient-Centered Outcomes Research Institute (Other)

215

Enrollment

Locations

Arms

28.1

Anticipated Duration (Months)

71.7

Patients Per Site

2.6

Patients Per Site Per Month

Study Details

Study Description

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.

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-evaluated and if eligible 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.

Condition or Disease	Intervention/Treatment	Phase
Cirrhosis, Liver Portal Hypertension	Behavioral: Enhanced Usual Care Drug: Lactulose Behavioral: Investigator recommended exercise Behavioral: TeleTai-Chi (virtual)	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

215 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention 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-evaluated to continue into stage 2 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.Participants will be randomized in stage 1 to enhanced usual care or enhanced usual care plus lactulose. After 12 weeks participants will be re-evaluated to continue into stage 2 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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

May 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Enhanced usual care group Participants will be in stage 1 for approximately 12 weeks and then be re-evaluated. Participation will end the study if not qualified for 2nd stage.	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.
Experimental: Treatment (Lactulose) group plus enhanced usual care Participants will be in stage 1 for approximately 12 weeks and then be re-evaluated. Participation will end the study if not qualified for 2nd stage.	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 (if re-randomized).
Active Comparator: Enhanced usual care group followed by investigator recommended exercise This is considered stage 2 for 12 weeks (for eligible re-randomized participants).	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. 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.
Experimental: Treatment (Lactulose) plus enhanced usual care then TeleTai-Chi exercise classes This is considered stage 2 for 12 weeks (for eligible re-randomized participants)	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 (if re-randomized). Behavioral: 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 to connect devices to televisions will be provided.
Experimental: Enhanced usual care group followed by Tele-Tai Chi exercise classes This is considered stage 2 for 12 weeks (for eligible re-randomized participants)	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. Behavioral: 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 to connect devices to televisions will be provided.
Experimental: Treatment (Lactulose) plus enhanced usual care then recommended exercise This is considered stage 2 for 12 weeks (for eligible re-randomized participants)	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 (if re-randomized). 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.

Outcome Measures

Primary Outcome Measures

A hierarchical composite of events over 24 weeks: injurious falls, non-injurious falls, incident Hepatic Encephalopathy, and death [Baseline to 24 weeks (following stage 2)]
Composite outcome is defined as any of the following: Injurious Fall: Fracture, dislocation, cut, head injury, soft - tissue injury requiring hospitalization Non - Injurious Fall: Inadvertently coming to rest on the floor or lower level 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

Secondary Outcome Measures

Cognitive Function based on the Animal Naming Test (ANT) [Baseline to 24 weeks (following stage 2)]
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).
Days-alive and out-of-the-hospital [Baseline to 24 weeks (following stage 2)]
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).
Injurious Falls [Baseline to 24 weeks (following stage 2)]
Falls include: Fracture, dislocation, cut, head injury, soft - tissue injury requiring hospitalization.
Non-Injurious Falls [Baseline to 24 weeks (following stage 2)]
Non- Injurious Falls include: Inadvertently coming to rest on the floor or lower level
Incident Overt hepatic encephalopathy (HE) [Baseline to 24 weeks (following stage 2)]
Incident Overt HE includes: Acute disorientation requiring hospitalization or the initiation of HE - directed therapy, confirmed by a gastroenterologist or study investigator.
Death [Baseline to 24 weeks (following stage 2)]
Mortality with any cause

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 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)
Platelet count < 80/ units per liter (uL)
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 of lactulose
Took lactulose for non - HE reasons for >28 days 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 physical 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan	Ann Arbor	Michigan	United States	48109
2	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
3	Baylor Scott & White Research Institute (BSW)	Dallas	Texas	United States	75246