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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Long-chain Fatty Acid Transport Deficiency
• Intervention / Treatment: Drug: Triheptanoin (SpezialölÒ 107®); Dietary supplement: MCT (Medium-Chain Triglycerides)

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Santiago de Compostela, Spain
    • Hospital Clinico Universitario de Santiago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Triheptanoin	Drug: Triheptanoin (SpezialölÒ 107®); 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; Dietary supplement: MCT (Medium-Chain Triglycerides); 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
Active Comparator: MCT (Medium-Chain Triglycerides)	Drug: Triheptanoin (SpezialölÒ 107®); 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; Dietary supplement: MCT (Medium-Chain Triglycerides); 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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Maria Luz Couce Pico
• Collaborators: Fundación Ramón Domínguez
• Investigators: Study Chair: Mª Luz Couce Pico, Hospital Clinico Universitario de Santiago; Principal Investigator: Jaume Campistol Plana, Hospital Sant Joan de Déu. Barcelona; Principal Investigator: Mercedes Martínez-Pardo, Hospital Universitario Ramon y Cajal; Principal Investigator: Mónica Ruiz Pons, Hospital Clínico Universitario Ntra. Sra. de Candelaria. Tenerife; Principal Investigator: Mª Teresa García Silva, Hospital 12 de Octubre. Madrid; Principal Investigator: Pablo Sanjurjo, Hospital de Cruces de Baracaldo - Bilbao; Principal Investigator: Koldo Aldamiz, Hospital de Cruces de Baracaldo - Bilbao; Principal Investigator: Inmaculada García Jiménez, Hospital Universitario Miguel Servet, Zaragoza

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: March 22, 2013
• First Submitted That Met QC Criteria: July 25, 2014
• First Posted (Estimate): July 28, 2014

Study Record Updates

• Last Update Posted (Estimate): July 28, 2014
• Last Update Submitted That Met QC Criteria: July 25, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Triglycerides; Lipid Metabolism; Fatty Acids.
• Other Study ID Numbers: 2007/084; 2007-005578-29 (EudraCT Number)