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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

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Neutral Lipid Storage Disease Drug: Fibrate treatment Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effect of Fibrate Therapy in Two Patients With Neutral Lipid Storage Disease With Myopathy (NLSDM)
Study Start Date : August 2011
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2012

Arm Intervention/treatment
Experimental: Fibrate Treatment
Patients will be treated during 28 weeks with a fibrate to assess the effects of PPAR activation on the NLSDM disease.
Drug: Fibrate treatment
Patients will receive a dosage of 400mg Bezafibrate every day during 28 weeks

Primary Outcome Measures :
  1. 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.

  2. 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.

  3. Cardiac function [ Time Frame: 28 weeks ]
    Cardiac function will be measured with ultrasound and be assessed by 2 blinded cardiologists.

Secondary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • suffering from NLSDM

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 identifier (NCT number): NCT01527318

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Maastricht University Medical Center
Maastricht, Limburg, Netherlands, 6200MD
Sponsors and Collaborators
Maastricht University Medical Center

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Responsible Party: Maastricht University Medical Center Identifier: NCT01527318    
Other Study ID Numbers: MEC 11-3-013
First Posted: February 7, 2012    Key Record Dates
Last Update Posted: May 14, 2013
Last Verified: May 2013
Keywords provided by Maastricht University Medical Center:
Lipid accumulation
Additional relevant MeSH terms:
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Muscular Diseases
Lipid Metabolism, Inborn Errors
Ichthyosiform Erythroderma, Congenital
Metabolic Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism Disorders
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Infant, Newborn, Diseases
Skin Diseases
Clofibric Acid
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents