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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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.


Detailed Summary:
Sponsor: Maastricht University Medical Center

Current Primary Outcome:

  • 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.


Original Primary Outcome: Same as current

Current Secondary Outcome: 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.


Original Secondary Outcome: Same as current

Information By: Maastricht University Medical Center

Dates:
Date Received: January 16, 2012
Date Started: August 2011
Date Completion:
Last Updated: May 13, 2013
Last Verified: May 2013