Neutral Lipid Storage Disease Clinical Trial
— NLSDMOfficial title:
The Effect of Fibrate Therapy in Two Patients With Neutral Lipid Storage Disease With Myopathy (NLSDM)
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.
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 |
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Netherlands | Maastricht University Medical Center | Maastricht | Limburg |
Lead Sponsor | Collaborator |
---|---|
Maastricht University Medical Center |
Netherlands,
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
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 |
Status | Clinical Trial | Phase | |
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