The Effect of Fibrate Therapy in Two Patients With Neutral Lipid Storage Disease With Myopathy (NLSDM) (NLSDM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01527318
Recruitment Status : Completed
First Posted : February 7, 2012
Last Update Posted : May 14, 2013
Information provided by (Responsible Party):
Maastricht University Medical Center

January 16, 2012
February 7, 2012
May 14, 2013
August 2011
December 2012   (Final data collection date for primary outcome measure)
  • mitochondrial function [ Time Frame: 28 weeks ]
    mitochondrial function will be measured in vivo with 1H-MRS by pCr-recovery and ex vivo by high resolution respirometry.
  • lipid accumulation [ Time Frame: 28 weeks ]
    Lipid accumulation will be measured both by 1H-MRS as CH/H2O ratio's in the Tibialis anterior muscle, as well as quantified from skeletal muscle biopsy with ORO from the vastus lateralis muscle.
  • Cardiac function [ Time Frame: 28 weeks ]
    Cardiac function will be measured with ultrasound and be assessed by 2 blinded cardiologists.
Same as current
Complete list of historical versions of study NCT01527318 on Archive Site
Insulin sensitivity [ Time Frame: 28 weeks ]
This will be assessed by an euglycemic hyperinsulenemic clamp and whole body isulin sensitivity will be expressed with the M-value.
Same as current
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The Effect of Fibrate Therapy in Two Patients With Neutral Lipid Storage Disease With Myopathy (NLSDM)
The Effect of Fibrate Therapy in Two Patients With Neutral Lipid Storage Disease With Myopathy (NLSDM)

Neutral Lipid Storage Disease With Myopath (NLSDM) is a disease caused by a defect in the PNPLA2 gene encoding ATGL. Patients with NLSDM accumulate triglycerides and exhibit muscle weakness, cardiac failure and hepatosteatosis. Most of these patients die at young age due to cardiac failure. Not much is known about the underlying mechanisms, though recently it was discovered that PPAR activation in ATGL-/- mice was impaired leading to decreased mitochondrial function, lipid accumulation and cardiac failure resulting in death at young age. Activation of PPARs, by treatment with fibrates rescued the phenotype and reduced mortality rates in these mice. These findings may have a major impact for patients with NLSDM if these results can be translated to humans. Therefore, the investigators would like to evaluate the beneficial effects of fibrate treatment on muscle mitochondrial and cardiac function in patients with NLSDM.

Patients will be treated with fibrates during a period of 28 weeks. Baseline measurements will be performed prior to the study and after treatment. Cardiac and muscular lipid accumulation, cardiac function, mitochondrial function and insulin sensitivity will be assessed during these baseline measurements.

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Phase 4
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Neutral Lipid Storage Disease
Drug: Fibrate treatment
Patients will receive a dosage of 400mg Bezafibrate every day during 28 weeks
Experimental: Fibrate Treatment
Patients will be treated during 28 weeks with a fibrate to assess the effects of PPAR activation on the NLSDM disease.
Intervention: Drug: Fibrate treatment
Haemmerle G, Moustafa T, Woelkart G, Büttner S, Schmidt A, van de Weijer T, Hesselink M, Jaeger D, Kienesberger PC, Zierler K, Schreiber R, Eichmann T, Kolb D, Kotzbeck P, Schweiger M, Kumari M, Eder S, Schoiswohl G, Wongsiriroj N, Pollak NM, Radner FP, Preiss-Landl K, Kolbe T, Rülicke T, Pieske B, Trauner M, Lass A, Zimmermann R, Hoefler G, Cinti S, Kershaw EE, Schrauwen P, Madeo F, Mayer B, Zechner R. ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPAR-α and PGC-1. Nat Med. 2011 Aug 21;17(9):1076-85. doi: 10.1038/nm.2439.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
December 2012
December 2012   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • suffering from NLSDM
Sexes Eligible for Study: All
18 Years to 70 Years   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
MEC 11-3-013
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Not Provided
Maastricht University Medical Center
Maastricht University Medical Center
Not Provided
Not Provided
Maastricht University Medical Center
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP