Clinical trial NCT05367596: OPTIMIzing muScle Preservation in paTients wIth Cirrhosis
Official title: OPTIMIzing muScle Preservation in paTients wIth Cirrhosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Compensated Cirrhosis
Sarcopenia
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
First posted: 2022-05-10
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, controlled, open-label.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Compare changes in body composition in both diets
timeFrame: Baseline, 12 weeks and 24 weeks.
Secondary outcomes:
measure: Frailty, Subjective
timeFrame: Baseline, 12 weeks and 24 weeks.
measure: Frailty, Objective
timeFrame: Baseline, 12 weeks and 24 weeks.
measure: Health Related Quality of Life
timeFrame: Baseline, 12 weeks and 24 weeks.
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
Study officials:
affiliation: KUMC
name: Winston Dunn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: KUMC
name: Felicia Felicia Steger, PhD
role: PRINCIPAL_INVESTIGATOR
References: