Trial record 10 of 45 for:    Congenital Myopathy

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT01527318
First received: January 16, 2012
Last updated: May 13, 2013
Last verified: May 2013
  Purpose

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

  Eligibility

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

Inclusion Criteria:

  • suffering from NLSDM
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01527318

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

Additional Information:
Publications:
Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov 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:
NLSDM
Lipid accumulation

Additional relevant MeSH terms:
Muscular Diseases
Ichthyosiform Erythroderma, Congenital
Congenital Abnormalities
Lipidoses
Sphingolipidoses
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Lysosomal Storage Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Ichthyosis
Skin Abnormalities
Skin Diseases, Genetic
Infant, Newborn, Diseases
Keratosis
Skin Diseases
Clofibric Acid
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014