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

This study has been completed.
Information provided by (Responsible Party):
Maastricht University Medical Center Identifier:
First received: January 16, 2012
Last updated: May 13, 2013
Last verified: May 2013

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 Intervention Phase
Neutral Lipid Storage Disease
Drug: Fibrate treatment
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effect of Fibrate Therapy in Two Patients With Neutral Lipid Storage Disease With Myopathy (NLSDM)

Resource links provided by NLM:

Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • mitochondrial function [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Cardiac function will be measured with ultrasound and be assessed by 2 blinded cardiologists.

Secondary Outcome Measures:
  • Insulin sensitivity [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
    This will be assessed by an euglycemic hyperinsulenemic clamp and whole body isulin sensitivity will be expressed with the M-value.

Enrollment: 6
Study Start Date: August 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • suffering from NLSDM
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Please refer to this study by its identifier: NCT01527318

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

Additional Information:
Responsible Party: Maastricht University Medical Center Identifier: NCT01527318     History of Changes
Other Study ID Numbers: MEC 11-3-013 
Study First Received: January 16, 2012
Last Updated: May 13, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht University Medical Center:
Lipid accumulation

Additional relevant MeSH terms:
Ichthyosiform Erythroderma, Congenital
Lipid Metabolism, Inborn Errors
Metabolic Diseases
Muscular Diseases
Congenital Abnormalities
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lipid Metabolism Disorders
Metabolism, Inborn Errors
Musculoskeletal Diseases
Nervous System Diseases
Neuromuscular Diseases
Skin Abnormalities
Skin Diseases
Skin Diseases, Genetic
Clofibric Acid
Anticholesteremic Agents
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action processed this record on May 25, 2016