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Mechanisms of Malnutrition in Cirrhosis With Portosystemic Shunting

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ClinicalTrials.gov Identifier: NCT03121404
Recruitment Status : Recruiting
First Posted : April 20, 2017
Last Update Posted : July 22, 2019
Sponsor:
Information provided by (Responsible Party):
Srinivasan Dasarathy, The Cleveland Clinic

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.

Condition or disease Intervention/treatment
Cirrhosis Procedure: Rectus abdominis muscle biopsy

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Mechanisms of Malnutrition in Cirrhosis With Portosystemic Shunting
Actual Study Start Date : November 14, 2008
Estimated Primary Completion Date : December 31, 2025
Estimated Study Completion Date : December 31, 2027

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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).
Procedure: 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.

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.
Procedure: 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.




Primary Outcome Measures :
  1. Determine the difference in myostatin expression between healthy control and cirrhosis patients [ Time Frame: 15 minute biopsy ]
    The primary outcome of this study is to determine the difference in expression of myostatin in skeletal muscle in a one time biopsy of the Rectus abdominis muscle between healthy controls and cirrhotic patients.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients will be identified from the Cleveland Clinic transplant list. All subjects with cirrhosis of any etiology who will undergo liver transplantation will make up the group of cirrhosis patients. The controls will be patients without cirrhosis that are undergoing abdominal surgery will be identified from the operating room list at Cleveland Clinic. Rectus abdominis muscle biopsies will be obtained directly after induction of anesthesia for the procedure.
Criteria

Inclusion Criteria:

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

Control

  1. non liver transplant donor
  2. Elective abdominal surgery (cholecystectomy, diverticulosis, acute gastrointestinal bleeding in the absence of exclusion criteria)

Exclusion Criteria:

  • Exclusion criteria (all subjects)
  • 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

Exclusion criteria (controls)

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03121404


Contacts
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Contact: Annette Bellar, MSLA 216-636-5247 bellara@ccf.org
Contact: Revathi Penumatsa penumar@ccf.org

Locations
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United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Annette Bellar, BS    216-636-5247    bellara@ccf.org   
Contact: Megan Villareal, BS    216-636-5247    villarm@ccf.org   
Principal Investigator: Srinivasan Dasarathy, MD         
Sponsors and Collaborators
The Cleveland Clinic

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Responsible Party: Srinivasan Dasarathy, Staff Physician, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT03121404     History of Changes
Other Study ID Numbers: 08-546
First Posted: April 20, 2017    Key Record Dates
Last Update Posted: July 22, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Fibrosis
Liver Cirrhosis
Malnutrition
Pathologic Processes
Liver Diseases
Digestive System Diseases
Nutrition Disorders