OPTIMIzing muScle Preservation in paTients wIth Cirrhosis

NCT05367596 | Completed DMC

• 1 other identifier: STUDY00148145
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity; Compensated Cirrhosis; Sarcopenia

Outcome Measures

Primary Outcomes (1)

• Compare changes in body composition in both diets

  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.

  Baseline, 12 weeks and 24 weeks.

Secondary Outcomes (3)

• Frailty, Subjective

  Baseline, 12 weeks and 24 weeks.

• Frailty, Objective

  Baseline, 12 weeks and 24 weeks.

• Health Related Quality of Life

  Baseline, 12 weeks and 24 weeks.

Study Arms (2)

Continuous Energy Restriction (CER)

EXPERIMENTAL

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.

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

Alternate-Day Moderate Fasting (ADMF).

EXPERIMENTAL

Alternate-Day Moderate Fasting (ADMF). Participants in both groups will have a daily late-evening snack and participate in remotely supervised exercises.

Behavioral: Alternate Day Modified Fasting (ADMF); Behavioral: Group Health Education Sessions; Behavioral: Late Evening Snack; Behavioral: Physical activity; Behavioral: Self-monitoring; Behavioral: Remotely Supervised Exercise Sessions

Interventions

Continuous Energy Restriction (CER) BEHAVIORAL

Energy intake will be prescribed at approximately 1,200-1,500 kcal/day with high protein. The diet will consist of low-calorie shakes provided by the study, as well as commercially available portion-controlled entrées, fruits/vegetables, and low energy-density foods available in grocery stores.

Continuous Energy Restriction (CER)

Alternate Day Modified Fasting (ADMF) BEHAVIORAL

Enhanced Care participants will have an alternate between three days of very-low energy intake (VLED; approximately 600-800 kcal/d) and four days of healthy eating (HE) each week. On HE days, participants will consume foods ad libitum for satiety.

Alternate-Day Moderate Fasting (ADMF).

Group Health Education Sessions BEHAVIORAL

Using video conferencing, all participants will attend weekly approximately 45-60 minutes group health education sessions led by a registered dietitian. The session will deliver a comprehensive nutritional and lifestyle change program to promote lifestyle changes and improve compliance.

Alternate-Day Moderate Fasting (ADMF).; Continuous Energy Restriction (CER)

Late Evening Snack BEHAVIORAL

The participants will have a late evening snack with a protein supplement.

Alternate-Day Moderate Fasting (ADMF).; Continuous Energy Restriction (CER)

Physical activity BEHAVIORAL

All participants will be prescribed moderate-intensity aerobic activities that do not require access to specialized exercise facilities.

Alternate-Day Moderate Fasting (ADMF).; Continuous Energy Restriction (CER)

Self-monitoring BEHAVIORAL

Weekly data related to adherence, food intake, physical activity, weight measurement, and nonserious adverse events will be self-reported via a REDCap survey. Participants will also be provided with a wireless activity tracker to measure total physical activity and intensity of activity objectively. These data will be used to counsel participants in addition to providing valuable feasibility data.

Alternate-Day Moderate Fasting (ADMF).; Continuous Energy Restriction (CER)

Remotely Supervised Exercise Sessions BEHAVIORAL

Sessions of 45 minutes duration will be delivered via video conferencing 2-3 times per week.

Alternate-Day Moderate Fasting (ADMF).; Continuous Energy Restriction (CER)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Kansas Medical Center: lead

Study Sites (1)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Related Publications (1)

• Dunn W, Herrmann SD, Montgomery RN, Hastert M, Honas JJ, Rachman J, Donnelly JE, Steger FL. Optimizing muscle preservation during weight loss in patients with cirrhosis: A pilot study comparing continuous energy restriction to alternate-day modified fasting for weight loss in patients with obesity and non-alcoholic cirrhosis of the liver. Obes Sci Pract. 2024 Oct 24;10(5):e70016. doi: 10.1002/osp4.70016. eCollection 2024 Oct.

  PMID: 39450267 DERIVED

MeSH Terms

Conditions

Obesity; Sarcopenia

Interventions

Exercise; Blood Glucose Self-Monitoring

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Monitoring, Physiologic; Self-Testing; Self Care; Therapeutics; Investigative Techniques

Study Officials

• Winston Dunn, MD

  KUMC

  PRINCIPAL INVESTIGATOR

• Felicia Felicia Steger, PhD

  KUMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Randomized, controlled, open-label.

Study Record Dates

• First Submitted: May 2, 2022
• First Posted: May 10, 2022
• Study Start: June 22, 2022
• Primary Completion: December 16, 2022
• Study Completion: December 16, 2022
• Last Updated: February 9, 2023

Record last verified: 2023-02

Locations

US (1)