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

History of Changes

Tracking Information
First Received Date ^ICMJE	January 16, 2012
Last Updated Date	May 13, 2013
Start Date ^ICMJE	August 2011
Primary Completion Date	December 2012 (final data collection date for primary outcome measure)
Current Primary Outcome Measures ^ICMJE (submitted: February 6, 2012)	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.
Original Primary Outcome Measures ^ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01527318 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ^ICMJE (submitted: February 6, 2012)	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.
Original Secondary Outcome Measures ^ICMJE	Same as current
Current Other Outcome Measures ^ICMJE	Not Provided
Original Other Outcome Measures ^ICMJE	Not Provided

Descriptive Information
Brief Title ^ICMJE	The Effect of Fibrate Therapy in Two Patients With Neutral Lipid Storage Disease With Myopathy (NLSDM)
Official Title ^ICMJE	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 Description	Not Provided
Study Type ^ICMJE	Interventional
Study Phase	Phase 4
Study Design ^ICMJE	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Condition ^ICMJE	Neutral Lipid Storage Disease
Intervention ^ICMJE	Drug: Fibrate treatment Patients will receive a dosage of 400mg Bezafibrate every day during 28 weeks
Study Arm (s)	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
Publications *	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-? and PGC-1. Nat Med. 2011 Aug 21;17(9):1076-85.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information
Recruitment Status ^ICMJE	Completed
Enrollment ^ICMJE	6
Completion Date	December 2012
Primary Completion Date	December 2012 (final data collection date for primary outcome measure)
Eligibility Criteria ^ICMJE	Inclusion Criteria: suffering from NLSDM
Gender	Both
Ages	18 Years to 70 Years
Accepts Healthy Volunteers	No
Contacts ^ICMJE	Contact information is only displayed when the study is recruiting subjects
Location Countries ^ICMJE	Netherlands

Administrative Information
NCT Number ^ICMJE	NCT01527318
Other Study ID Numbers ^ICMJE	MEC 11-3-013
Has Data Monitoring Committee	No
Responsible Party	Maastricht University Medical Center
Study Sponsor ^ICMJE	Maastricht University Medical Center
Collaborators ^ICMJE	Not Provided
Investigators ^ICMJE	Not Provided
Information Provided By	Maastricht University Medical Center
Verification Date	May 2013
^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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