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

Neutral Lipid Storage Disease Clinical Trial

— NLSDM  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01527318
• Other study ID #: MEC 11-3-013
• Status: Completed
• Phase: Phase 4
• First received: January 16, 2012
• Last updated: May 13, 2013
• Start date: August 2011
• Est. completion date: December 2012

Study information

• Verified date: May 2013
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• suffering from NLSDM

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lipid Metabolism, Inborn Errors
• Muscular Diseases
• Neutral Lipid Storage Disease

Intervention

Drug:
• Fibrate treatment
Patients will receive a dosage of 400mg Bezafibrate every day during 28 weeks

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center	Maastricht	Limburg

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

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-a and PGC-1. Nat Med. 2011 Aug 21;17(9):1076-85. doi: 10.1038/nm.2439. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	mitochondrial function	mitochondrial function will be measured in vivo with 1H-MRS by pCr-recovery and ex vivo by high resolution respirometry.	28 weeks	No
Primary	lipid accumulation	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.	28 weeks	No
Primary	Cardiac function	Cardiac function will be measured with ultrasound and be assessed by 2 blinded cardiologists.	28 weeks	No
Secondary	Insulin sensitivity	This will be assessed by an euglycemic hyperinsulenemic clamp and whole body isulin sensitivity will be expressed with the M-value.	28 weeks	No

External Links

•   Research group information site