A Comparative Phase 2 Study Assessing the Efficacy of Triheptanoin, an Anaplerotic Therapy in Huntington's Disease

A Comparative Phase 2 Study Assessing the Efficacy of Triheptanoin, an Anaplerotic Therapy in Huntington's Disease

In the study the investigators plan to include 100 early affected HD patients (5 ≤ UHDRS ≤ 40) in a randomized, double-blind, controlled study in 2 centers (France and the Netherlands). Patients will receive either triheptanoin at 1g/kg of body weight per day (n = 50), or a control oil (n = 50) at 1g/kg of body weight per day for 6 months followed by an open label phase using triheptanoin for another 6 months. Efficacy of triheptanoin will be evaluated by measurements of caudate volume using volumetric magnetic resonance imaging. Clinical improvement will be evaluated by brain energy metabolism quantification as evaluated by the ratio of inorganic phosphate/phosphocreatine, during visual stimulation, using 31P-MRS, UHDRS, TFC, and PBA-S scores as well as performance on the neuropsychological battery. Patient quality of life will be evaluated with the SF-36 questionnaire before and after treatment; biological tolerance and compliance will be evaluated by routine biochemical blood tests, plasma and urine measurements of triheptanoin oil derivatives and patient report.

Inclusion Criteria:

• Positive genetic test with CAG repeat length ≥39 in HTT gene
• At least 18 years of age
• Signature of informed consent
• Covered by social security
• UHDRS score between 5 and 40
• Ability to undergo MRI scanning
• BMI between 18 and 30

Exclusion Criteria:

• Hypersensitivity to triheptanoin or to one of its excipients
• Additional major comorbidities
• History of severe head injury
• Participation in another therapeutic trial (3 month exclusion period)
• For women of childbearing age, the absence of two forms of effective contraception (with the exception of those who are abstinent)
• Pregnancy or breastfeeding
• Inability to understand information about the protocol
• Persons deprived of their liberty by judicial or administrative decision
• Adult subject under legal protection or unable to consent
• Treatment with tetrabenazine