Trial document




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  DRKS00007781

Trial Description

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Title

Effect of dietary lipid modification on nonalcoholic fatty liver disease in carriers of the PNPLA3 I148M genetic variant: an open label trial

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

PNPLA3 is a protein found in the liver which helps to break down unsaturated fatty acids. A genetic mutation, specifically, the PNPLA3 148M substitution, lowers the potential to break down these unsaturated fatty acids. This could lead to a build-up of these fatty acids in the liver. Interestingly, the consumption of unsaturated fatty acids (e.g. Mediterranean diet) is recommended for dyslipidemia and fatty liver. Based on this we predict that not all individuals will have the same response to a diet high in unsaturated fatty acids, and that it will depend on the genetic make-up. We therefore want to carry out an intervention study, whereby individuals with various genetic mutations receive unsaturated fatty acids, and are followed up for several weeks, to see what, if any effect the dietary change has on liver fat contents.

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Brief Summary in Scientific Language

Romeo and colleagues were the first to discover a clear risk for NAFLD with a genetic variation of the patatin-like phospholipase family (PNPLA3) . PNPLA3 is a protein expressed in the liver with an intracellular lipase activity that is more pronounced against unsaturated fatty acids. The PNPLA3 148M substitution cause a loss of function of enzymatic activity with regards unsaturated fatty acids. Interestingly, the consumption of unsaturated fatty acids (e.g. Mediterranean diet) is recommended for dyslipidemia and hepatic steatosis. Based on this we predict that PNPLA3 wild type individuals will have the most benefits from the dietary change with polyunsaturated fatty acids (PUFA), as compared to homozygotes for the PNPLA3 148M mutation, in who long term dietary PUFA intake may actually be detrimental. The goal of this pilot study is to carry you a dietary lipid modification study in both PNPLA3 wild type individuals as well as in those that are homozygous for the PNPLA3 148M mutation.


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Organizational Data

  •   DRKS00007781
  •   2015/03/25
  •   [---]*
  •   yes
  •   Approved
  •   148/14, Ethik-Kommission bei der Ärztekammer des Saarlandes
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Secondary IDs

  •   U1111-1167-4868 
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Health Condition or Problem studied

  •   K76.0 -  Fatty (change of) liver, not elsewhere classified
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Interventions/Observational Groups

  •   After following a two week run-in phase, subjects will be given omega 3 supplements (4g p.o. contained in 1 tablet daily) for 4 weeks.
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Characteristics

  •   Interventional
  •   [---]*
  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   N/A
  •   N/A
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Primary Outcome

Changes in hepatic steatosis, as assessed using controlled attentuation parameter (CAP) after 4 weeks of oral omega-3 supplementation

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Secondary Outcome

Changes to the following paramters after 4 weeks of oral omega 3 supplementation:

•Blood lipid profile (Total cholesterol, LDL-C, HDL-C, triglycerides)
•Liver function tests (e.g. AST, ALT, GGT, AP, Bilirubin, Albumin)
•Inflammatory markers
•Fasting plasma glucose, insulin and HbA1c
•Liver stiffness measurement (LSM)

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2015/03/27
  •   20
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

1. Patients with non-alcoholic fatty liver disease
2. Patients with the PNPLA3-Genotype (p.148MM and p.I148II)

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Exclusion Criteria

•Known infection with viral hepatitis, HIV or cholestatic liver diseases (e.g. PBC, PSC).
•Presence of Diabetes Mellitus Type 2 (HbA1c ≥ 7.5% (≥ 58 mmol/mol)
•Presence of Alcoholic Fatty Liver Disease
with a weekly alcohol consumption of > 21 drinks (> 30 g alcohol/Day) in men and >14 drinks (> 20 g alcohol/Day) in women (2)
•Presence of liver cirrhosis based on liver stiffness measurement (transient elastography ≥ 13kPa FibroScan®,Echosens, Paris, France)
•Medications known to increase fatty liver (e.g. Amiodarone, Methotrexat) or to affect carbohydrate or lipid metabolism?
•Pregnancy
•Pacemaker
•Vegetarians or vegans

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Addresses

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    • Saarland University Medical Center
    • Mr.  Prof.  Frank  Lammert 
    • Department of Internal Medicine II, Kirrberger Str. 100
    • 66421  Homburg
    • Germany
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    • The Wallenberg LaboratorySahlgrenska University Hospital
    • Mr.  Prof. Dr.  Stefano  Romeo 
    • Bruna Stråket 16
    • 41345  Göteborg
    • Sweden
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    • Saarland University Medical Center
    • Ms.  Dr.  Caroline  Stokes 
    • Department of Internal Medicine II, Kirrberger Str. 1
    • 66421  Homburg
    • Germany
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    • Saarland University Medical Center
    • Ms.  Dr.  Caroline  Stokes 
    • Department of Internal Medicine II, Kirrberger Str. 1
    • 66421  Homburg
    • Germany
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Sources of Monetary or Material Support

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    • Saarland University Medical Center
    • Mr.  Prof.  Frank  Lammert 
    • Department of Internal Medicine II, Kirrberger Str. 100
    • 66421  Homburg
    • Germany
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    • The Wallenberg LaboratorySahlgrenska University Hospital
    • Mr.  Prof. Dr.  Stefano  Romeo 
    • Bruna Stråket 16
    • 41345  Göteborg
    • Sweden
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Status

  •   Recruiting complete, follow-up complete
  •   2016/12/20
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.