MedPath

OPTIMIzing muScle Preservation in paTients wIth Cirrhosis

Not Applicable
Completed
Conditions
Compensated Cirrhosis
Sarcopenia
Obesity
Interventions
Behavioral: Alternate Day Modified Fasting (ADMF)
Behavioral: Continuous Energy Restriction (CER)
Behavioral: Group Health Education Sessions
Behavioral: Late Evening Snack
Behavioral: Physical activity
Behavioral: Self-monitoring
Behavioral: Remotely Supervised Exercise Sessions
Registration Number
NCT05367596
Lead Sponsor
University of Kansas Medical Center
Brief Summary

Patients with obesity and cirrhosis benefit from weight loss but are prone to sarcopenia (loss of muscle mass, strength, and function).

This study proposes to test a specialized weight loss program Alternative-day Modified Fasting (ADMF) designed to promote weight loss and preserve skeletal muscle mass, strength, and function in patients with both Child-Pugh (CP) class A cirrhosis and obesity. This study will compare the effectiveness of the ADMF to Continuous Energy Restriction (CER) for 24-weeks. Both arms will receive a high-protein, high-BCAA diet, a late-night snack, supervised aerobic and resistance exercise, increased physical activity through self-monitoring, and group behavioral counseling.

The primary aim of this trial is to evaluate the feasibility and acceptability of ADMF and CER for 6 months in patients with cirrhosis and obesity. The secondary aim is to compare changes in body composition in both diets.

Detailed Description

Patients with both cirrhosis and obesity benefit from weight loss, though patients with cirrhosis are prone to sarcopenia due to accelerated rates of protein turnover, and weight loss typically involves 20-30% of weight loss from lean mass. Prior research indicates that increased intake of high-quality protein, reduced fasting duration, and regular physical activity (particularly resistance training) can improve body composition in patients with cirrhosis. However, weight loss programming specifically tailored to retain lean mass in patients with cirrhosis has not been thoroughly investigated. Further, preliminary data suggests that alternate-day modified fasting, a form of intermittent fasting, may promote lean mass retention during weight loss. Here, this study will compare a weight loss program in patients with both Child-Pugh Class A cirrhosis and obesity using either a standard low-calorie diet (1,200 - 1,500 kcal/day) or alternate day modified fasting featuring a very-low-calorie diet 2-3 days per week for feasibility, satisfaction, and changes in body composition. Both groups will receive a behavioral weight loss program featuring portion-controlled meals and supervised group exercise.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
20
Inclusion Criteria
  • Subjects ≥18 years of age. Per the NIH Policy NOT-OD-18-116, we will include adults ≥ 65 yrs.

  • Subjects have a BMI of 30-45. Body mass index (BMI) of 25 to 45 kg/m2. Individuals with a BMI< 25 kg/m2 are not overweight, and individuals with a BMI >45 kg/m2 require more aggressive weight-loss interventions such as bariatric surgery.

  • Subjects has a diagnosis of cirrhosis based on any of the following methods

    • Liver Biopsy is consistent with stage IV fibrosis according to the NASH Clinical Research Network (CRN) scoring system.
    • Fibroscan Liver Stiffness >14kpa
    • Endoscopy or imaging finding of varices
Exclusion Criteria
  • Child-Pugh (CP) score currently > 6 (i.e., CP Class B/C cirrhosis).
  • History of ascites.
  • History of portal system encephalopathy.
  • Prior history of liver cancer.
  • Prior history of non-melanoma skin cancer within the last five years
  • Hepatitis C Virus (HCV) patients who have not undergone sustained virological response (SVR).
  • Hepatitis B Virus (HBV) Patients who have not received antiviral treatment.
  • Patients with diabetes currently on insulin and or sulfonylureas.
  • Active alcohol use >7 drinks per week in the past six months.
  • Suspected eating disorders based on Eating Attitudes Test (EAT-26) and The Binge Eating Scale (BES):
  • Unable to participate in moderate-intensity PA, e.g., brisk walking
  • Participation in a structured weight loss program in the previous six mos.
  • Not weight stable (5%) for three months prior to intake.
  • Unwilling to be randomized.
  • Pregnancy during the previous six mos., currently lactating, or planned pregnancy in the following six mos
  • Current use of antipsychotics, untreated depression, or other psychiatric illnesses would preclude weight management participation.
  • Adherence to specialized diets that would make it difficult or impossible to follow the guidelines for intervention.
  • Evidence of eating disorder or binge eating (as assessed by the Eating Attitudes Test and or Binge Eating Scale.)
  • Do not have access to a wireless equipment necessary for remotely delivered group and exercise classes.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Alternate-Day Moderate Fasting (ADMF).Remotely Supervised Exercise SessionsAlternate-Day Moderate Fasting (ADMF). Participants in both groups will have a daily late-evening snack and participate in remotely supervised exercises.
Alternate-Day Moderate Fasting (ADMF).Group Health Education SessionsAlternate-Day Moderate Fasting (ADMF). Participants in both groups will have a daily late-evening snack and participate in remotely supervised exercises.
Continuous Energy Restriction (CER)Late Evening SnackContinuous energy restriction (CER; 1,200-1,500 kcal/day). Participants in both groups will have a daily late-evening snack and participate in remotely supervised exercises.
Alternate-Day Moderate Fasting (ADMF).Alternate Day Modified Fasting (ADMF)Alternate-Day Moderate Fasting (ADMF). Participants in both groups will have a daily late-evening snack and participate in remotely supervised exercises.
Alternate-Day Moderate Fasting (ADMF).Late Evening SnackAlternate-Day Moderate Fasting (ADMF). Participants in both groups will have a daily late-evening snack and participate in remotely supervised exercises.
Alternate-Day Moderate Fasting (ADMF).Self-monitoringAlternate-Day Moderate Fasting (ADMF). Participants in both groups will have a daily late-evening snack and participate in remotely supervised exercises.
Continuous Energy Restriction (CER)Continuous Energy Restriction (CER)Continuous energy restriction (CER; 1,200-1,500 kcal/day). Participants in both groups will have a daily late-evening snack and participate in remotely supervised exercises.
Continuous Energy Restriction (CER)Group Health Education SessionsContinuous energy restriction (CER; 1,200-1,500 kcal/day). Participants in both groups will have a daily late-evening snack and participate in remotely supervised exercises.
Continuous Energy Restriction (CER)Physical activityContinuous energy restriction (CER; 1,200-1,500 kcal/day). Participants in both groups will have a daily late-evening snack and participate in remotely supervised exercises.
Continuous Energy Restriction (CER)Self-monitoringContinuous energy restriction (CER; 1,200-1,500 kcal/day). Participants in both groups will have a daily late-evening snack and participate in remotely supervised exercises.
Continuous Energy Restriction (CER)Remotely Supervised Exercise SessionsContinuous energy restriction (CER; 1,200-1,500 kcal/day). Participants in both groups will have a daily late-evening snack and participate in remotely supervised exercises.
Alternate-Day Moderate Fasting (ADMF).Physical activityAlternate-Day Moderate Fasting (ADMF). Participants in both groups will have a daily late-evening snack and participate in remotely supervised exercises.
Primary Outcome Measures
NameTimeMethod
Compare changes in body composition in both dietsBaseline, 12 weeks and 24 weeks.

The primary outcome is the percent of weight lost as fat-free mass at 24 weeks. Body weight and body composition (as assessed by dual x-ray absorptiometry) will be measured at baseline, week 12, and post-intervention. Percent weight loss from fat-free mass will be calculated as \[Δ fat-free mass / Δ weight loss\] for all participants who lose at least 3% of initial body weight. If \>70% of participants lose at least 80% of weight from fat mass (or no more than 20% of weight loss coming from lean mass) we will proceed to testing this intervention in an adequately powered trial.

Secondary Outcome Measures
NameTimeMethod
Frailty, SubjectiveBaseline, 12 weeks and 24 weeks.

Karnofsky Performance Status (KPS). The KPS allows patients to be classified as to their functional impairment. This can be used to compare effectiveness of different therapies and to assess the prognosis in individual patients. The lower the KPS, the worse the survival for most serious illnesses.

Frailty, ObjectiveBaseline, 12 weeks and 24 weeks.

The Liver Frailty Index (LFI), composed of 3 performance-based tests (grip strength, chair stands, and balance), is a tool specifically developed in patients with cirrhosis to objectively measure physical function, a critical determinant of health outcomes.

Health Related Quality of LifeBaseline, 12 weeks and 24 weeks.

Health-related quality of life (HRQOL) is a multi-dimensional concept commonly used to examine the impact of health status on quality of life. HRQOL is often measured by four core questions that asked about general health status and number of unhealthy days.

Trial Locations

Locations (1)

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

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