Mechanisms of Malnutrition in Cirrhosis With Portosystemic Shunting

NCT ID: NCT03121404

Last Updated: 2026-01-09

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-11-14
• Study Completion Date: 2027-12-31

Brief Summary

Cirrhosis is characterized by loss of muscle as well as fat mass, which increases morbidity and mortality before, during, and after liver transplantation. A common mechanism for the reduced muscle and fat mass in cirrhosis is an increased expression of the TGF (transforming growth factor)beta superfamily member, myostatin, in the muscle and adipose tissue. The present study will examine the expression of myostatin, its receptor and intracellular signaling pathways in the skeletal muscle and mesenteric adipose tissue in cirrhotic patients undergoing liver transplantation as compared to healthy controls undergoing planned abdominal surgery. 16 cirrhotic patients will be identified from the transplant list, and 16 healthy controls from outpatient surgery lists. Nutritional assessment will be performed, including anthropometry (triceps skinfold thickness, mid arm circumference), dual energy x-ray absorptiometry (DEXA), and bioelectrical impedance analysis (BIA). Rectus abdominis muscle tissue and omental fat tissue will be harvested in the operating room, and the expression of signaling proteins involved in skeletal muscle protein synthesis will be quantified. The investigator will also quantify the expression of genes involved in lipolysis and lipid synthesis. The investigator anticipates that the expression of myostatin will be higher in the skeletal muscle and adipose tissue of cirrhotics as compared to controls. There will be a reduction in the expression of the signaling proteins that regulate skeletal muscle protein synthesis, as well as the expression of genes regulating lipogenesis. The increased expression of myostatin will also correlate with reduced anthropometric and DEXA measurements of lean body mass and fat mass.

Conditions

Cirrhosis

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Cirrhosis Patient

Patients will be identified from the transplant list. Inclusion criteria will be all subjects with cirrhosis of any etiology who will undergo liver transplantation. . Rectus abdominis muscle biopsy will be obtained directly after induction of anesthesia for the procedure. In addition patients will have anthropometric measurements taken within 2 weeks of surgery. For the cirrhotic patients this includes hand grip test and dual energy x-ray absorption (DEXA).

Rectus abdominis muscle biopsy

Intervention Type: PROCEDURE

Patients who will already be having either liver transplant surgery or abdominal surgery will have a biopsy of their rectus abdominis muscle during the time of surgery.

Healthy Controls

Controls will be identified from the abdominal surgery operating room lists at Cleveland Clinic. Rectus abdominis muscle biopsy will be obtained directly after induction of anesthesia for the procedure. In addition patients will have anthropometric measurements taken within 2 weeks of surgery which will not include DEXA or hand grip test.

Rectus abdominis muscle biopsy

Intervention Type: PROCEDURE

Patients who will already be having either liver transplant surgery or abdominal surgery will have a biopsy of their rectus abdominis muscle during the time of surgery.

Interventions

Rectus abdominis muscle biopsy

Patients who will already be having either liver transplant surgery or abdominal surgery will have a biopsy of their rectus abdominis muscle during the time of surgery.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Age 18-70 years
• Patients undergoing abdominal surgery (liver transplantation or other surgery)

Control

1. non liver transplant donor

Exclusion Criteria

• Average daily alcohol intake > 20 g in women and > 30 g in men
• Diabetes or a fasting serum glucose > 100 mg/dL
• Hyper- / hypo- thyroidism
• Renal disease with serum creatinine > 1.4 mg/dL
• Folate or vitamin B12 deficiency
• Active intravenous drug use
• History of bowel surgery or gastric bypass surgery
• Medications/supplements that affect fat mass or protein mass (creatine, glucocorticoids)
• Pregnancy
• Chronic diseases that result in cachexia (renal, cardiac, pulmonary, hematologic, cancer)
• Hepatocellular cancer

• Evidence of malnutrition as quantified by triceps skinfold thickness, mid arm muscle area and creatinine height index)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Srinivasan Dasarathy

Staff Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Annette Bellar, MSLA

Role: CONTACT

bellara@ccf.org

216-636-5247

Revathi Penumatsa

Role: CONTACT

penumar@ccf.org

Facility Contacts

Annette Bellar, BS

Role: primary

bellara@ccf.org

216-636-5247

Megan Villareal, BS

Role: backup

villarm@ccf.org

216-636-5247

Other Identifiers

08-546

Identifier Type: -

Identifier Source: org_study_id