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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01527318
Other study ID # MEC 11-3-013
Secondary ID
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


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
See also
  Status Clinical Trial Phase
Active, not recruiting NCT02635269 - Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy N/A
Recruiting NCT02918032 - International Registry Study of Neutral Lipid Storage Disease (NLSD) / Triglyceride Deposit Cardiomyovasculopathy (TGCV) and Related Diseases