Triheptanoin Treatment Trial for Patients With Long-chain Fatty Acid Beta-oxidation Defects

Study Overview
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Brief Summary
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The purpose of this study is to determine if administration Triheptanoin is an effective treatment for defects of the long-chain fatty acid beta-oxidation in young adults or adults. Period of treatment and follow-up will be 16 months.

Detailed Description
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Triheptanoin treatment, in patients with long-chain fatty acid beta-oxidation defects, could cause not only a great improvement in their quality of life, also could prevent life-threatening signs, reducing symptoms and serious complications of their disease, like cardiomyopathy, Reye-like syndrome episodes and rhabdomyolysis. This result would occur by the effect of propionyl CoA primer on the Krebs cycle and, at the same time, would produce a gluconeogenic effect. This treatment opens the door to be used in other diseases such as pyruvate carboxylase deficiency, glycogen storage disease and other diseases with energy problems. All patients will be followed up until 16 months.

Official Title
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Study to Evaluate the Effectiveness of Dietary Treatment With Triheptanoin in Patients With Long-chain Fatty Acid Beta-oxidation Defects

Conditions
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Long-chain Fatty Acid Transport Deficiency

Intervention / Treatment
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* Drug: Triheptanoin (SpezialölÒ 107®)
* Dietary Supplement: MCT (Medium-Chain Triglycerides)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients with any of the following conditions: Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency (LCHAD). Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCAD.) Mitochondrial trifunctional protein (MTP). Carnitine palmitoyltransferase I deficiency (CPT I). Carnitine Palmitoyltransferase II (CPT II). Carnitine-acylcarnitine translocase deficiency (CACT). Positive skin biopsy: patients were deemed to commence the dietary treatment with Triheptanoin after evaluating the individual response in vitro in cultured fibroblasts. This response is based on the measurement of the production of propionyl-CoA, the incubation with fatty acids odd-chain, compared with control group fibroblasts. The informed consent must be signed by the patient or family, in the case of minors. Exclusion Criteria: No patient/family collaboration or the application of dietary treatment. No in vitro test response. Do not meet the inclusion criteria.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Triheptanoin<br> | Drug: Triheptanoin (SpezialölÒ 107®)<br>* Randomization: Treatment with Triheptanoin for 6 months Washout Period: Treatment with MCT(Medium-Chain Triglycerides)for 2 months Crossover: Treatment with MCT(Medium-Chain Triglycerides)for 6 months<br>Dietary Supplement: MCT (Medium-Chain Triglycerides)<br>* Randomization: Treatment with MCT(Medium-Chain Triglycerides)for 6 months Washout Period: Treatment with MCT(Medium-Chain Triglycerides)for 2 months Crossover: Treatment with Triheptanoin for 6 months<br>|
| Active Comparator: MCT (Medium-Chain Triglycerides)<br> | Drug: Triheptanoin (SpezialölÒ 107®)<br>* Randomization: Treatment with Triheptanoin for 6 months Washout Period: Treatment with MCT(Medium-Chain Triglycerides)for 2 months Crossover: Treatment with MCT(Medium-Chain Triglycerides)for 6 months<br>Dietary Supplement: MCT (Medium-Chain Triglycerides)<br>* Randomization: Treatment with MCT(Medium-Chain Triglycerides)for 6 months Washout Period: Treatment with MCT(Medium-Chain Triglycerides)for 2 months Crossover: Treatment with Triheptanoin for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of metabolic decompensation. | This is a combined endpoint, including the number and/or severity of episodes of hypoglycemia, rhabdomyolysis, cardiomyopathy and liver failure after starting treatment with trihepatnoin. | up to 16 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in the profiles of acylcarnitines with control. |  | 6 months and 6 months in each arm treatment | 
| Average values of transaminase and creatin kinase. |  | 6 months and 6 months in each arm treatment | 
| Differences in the fatty acid composition of plasma and red blood cells. |  | 6 months and 6 months in each arm treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Triglycerides; Lipid Metabolism; Fatty Acids.