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Trial record 29 of 180 for:    Phospholipids

ER Stress in NAFLD

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ClinicalTrials.gov Identifier: NCT01807910
Recruitment Status : Withdrawn (The study was not funded)
First Posted : March 8, 2013
Last Update Posted : October 23, 2013
Sponsor:
Information provided by (Responsible Party):
Charles R. Flynn, Vanderbilt University

Brief Summary:
The investigators overall hypothesis is that exacerbation of endoplasmic reticulum (ER) stress in the liver is associated with significant alterations in phosphatidylcholines that drive the NASH phenotype in obese humans. The investigators plan to examine this hypothesis in a well-characterized cohort of obese subjects that are scheduled for bariatric surgery. Methyl-D9-choline chloride will be infused before and after a 2-week high fructose or glucose feeding to determine the biosynthesis and kinetics of secretory lipoprotein phospholipids. It is proposed that phospholipid metabolism play an important role in the pathogenesis or etiology of fatty liver in non-alcoholic conditions through mechanisms that invoke ER and oxidative stress responses.

Condition or disease Intervention/treatment Phase
Obesity NAFLD Drug: methyl-D9-choline Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: Phospholipid Endoplasmic Reticulum Stress in Nonalcoholic Fatty Liver Disease
Study Start Date : October 2013
Estimated Primary Completion Date : October 2017
Estimated Study Completion Date : April 2018


Arm Intervention/treatment
Experimental: Fructose
Participants will receive fructose (3g/kg/day) for 2 weeks.
Drug: methyl-D9-choline
Subjects in both arms will be infused with methyl-D9-choline in order to assess the biosynthesis and kinetics of secretory lipoprotein phospholipids.

Active Comparator: Glucose
Participants will receive glucose (3g/kg/day) for 2 weeks.
Drug: methyl-D9-choline
Subjects in both arms will be infused with methyl-D9-choline in order to assess the biosynthesis and kinetics of secretory lipoprotein phospholipids.




Primary Outcome Measures :
  1. Net hepatic phospholipid production [ Time Frame: Baseline and 2 weeks ]
    Net hepatic phospholipid production will be determined using [11C]choline dynamic Positron Emission Tomography (PET) before and after high fructose feeding for two weeks. A similar group of control obese subjects will undergo the same procedures before and after two weeks isocaloric glucose feeding.


Secondary Outcome Measures :
  1. Kinetics of secretory lipoprotein phospholipids [ Time Frame: Baseline and 2 weeks ]
    The biosynthesis and kinetics of secretory lipoprotein phospholipids will be determined using methyl-D9-choline chloride infusion before and after high fructose (or glucose) feeding.


Other Outcome Measures:
  1. Changes in zonation of phospholipids and PEMT in liver tissues [ Time Frame: 60 months ]
    Changes in zonation of phospholipids and PEMT in liver tissues acquired from the same subjects intraoperatively during bariatric surgery will be assessed using MALDI-IMS.



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Ages Eligible for Study:   30 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ambulatory females age 30-60 years old
  • Women of all ethnic groups
  • BMI≥35 kg/m2
  • Approval for Roux-en-Y gastric bypass or sleeve gastrectomy.

Exclusion Criteria:

  • Smoking >7 cigarettes per day
  • Previous malabsorptive or restrictive intestinal surgery
  • Pregnant or breastfeeding
  • Recent history of neoplasia (<5 years ago)
  • Malabsorptive syndromes
  • Inflammatory intestinal disease
  • Patients with established organ dysfunction
  • Diagnosis of type 1 or type 2 diabetes mellitus or current use of anti-diabetic medication (last 30 days; last 60days for thiazolidinediones)
  • Diagnosed hyperbetalipoproteinemia or hypobetalipoproteinemia
  • Patients on cholesterol lowering medicines
  • Vegan diet
  • Hepatic fat content <10% by MRI
  • Inability to comply with study protocol such as unable to make study visits or be available daily for phone contact
  • Any condition which would interfere with MRI or PET studies, e.g. claustrophobia, cochlear implant, chronic back pain limiting ability to lay flat, metal fragments in eyes, cardiac pacemaker, neural stimulator, tattoos with iron pigment and metallic body inclusions or other metal implanted in the body which may interfere with MRI scanning.

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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): NCT01807910


Locations
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United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
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Principal Investigator: Charles R Flynn, PhD Vanderbilt University Medical Center
Study Chair: Naji N Abumrad, MD Vanderbilt University Medical Center

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Responsible Party: Charles R. Flynn, Assistant Professor, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01807910     History of Changes
Other Study ID Numbers: ER stress
First Posted: March 8, 2013    Key Record Dates
Last Update Posted: October 23, 2013
Last Verified: October 2013

Keywords provided by Charles R. Flynn, Vanderbilt University:
Obesity
NAFLD
NASH
Steatosis

Additional relevant MeSH terms:
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Non-alcoholic Fatty Liver Disease
Fatty Liver
Liver Diseases
Digestive System Diseases
Choline
Lipotropic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents
Lipid Regulating Agents
Nootropic Agents