Clinical Trial: Bezafibrate Trial in CPT2 Deficiency
Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Interventional
Official Title: Clinical Trial on the Effect of Bezafibrate in the Muscular Form of Carnitine Palmitoyltransferase 2 Deficiency
Brief Summary: The purpose of this study is to determine whether bezafibrate is effective in the treatment of the muscular adult form of carnitine palmitoyltransferase 2 deficiency
Detailed Summary:
Fatty acids are the main source of energy for non-glucodependent tissues during fasting and prolonged exercise. Carnitine Palmitoyltransferase (CPT) 1 and 2 are a key-enzymes in the regulation of mitochondrial FAO, by governing entry of long-chain fatty acids within the mitochondrial matrix. CPT2 deficiency is among the most common inherited disorders of mitochondrial fatty acid oxidation (FAO). The neonatal and infantile forms of CPT2 deficiency are life-threatening diseases with a hepatocardiomuscular presentation. The adult form presents as recurrent attacks of rhabdomyolysis, mostly triggered by prolonged exercise, fasting, and infections, and is usually considered as a "mild" disease. However, patients commonly suffers permanent muscle weakness, and/or frequent (weekly, and sometimes daily) attacks of rhabdomyolysis, that occasionally result in severe episodes of acute renal insufficiency, and rarely in sudden death.
Difference in the clinical severity of the distinct forms of CPT2 deficiency correlates in some extent with in vitro data. Thus, when measured in fibroblasts or lymphocytes, the residual CPT2 activity and the long-chain fatty acid oxidation (LCFAO) are usually less than 10% of control values in the neonatal and infantile forms, while they most often are over 20 % of controls in the adult form.
Clinical management of CPT2-deficient patients remains poor, and most often does not succeed in significantly improving their clinical condition. Treatment mostly relies so far on restriction in lipid intake and limitation of fasting and exercise. We decided a few years ago to set up a project of pharmacological therapy for this disease, based upon in vitro testing of pharmacological agents potentially able to increase the residual enzymatic activity in CPT2-deficient cell lines. Some of the best "can
Sponsor: Assistance Publique - Hôpitaux de Paris
Current Primary Outcome: Rate of 3H-palmitate oxidation in the patients'lymphocytes and skeletal muscle
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Rate of CPT2 enzymatic activity in the patients'lymphocytes and skeletal muscle
- Rate of palmitoyl-L-carnitine oxidation in the patients' skeletal muscle
- Steady-state amount of CPT2 mRNA in the patients'skeletal muscle
Original Secondary Outcome: Same as current
Information By: Assistance Publique - Hôpitaux de Paris
Dates:
Date Received: June 9, 2006
Date Started: June 2006
Date Completion: July 2007
Last Updated: April 6, 2007
Last Verified: April 2007
