Clinical trial NCT02453061: A Comparative Phase 2 Study Assessing the Efficacy of Triheptanoin, an Anaplerotic Therapy in Huntington's Disease
Official title: A Comparative Phase 2 Study Assessing the Efficacy of Triheptanoin, an Anaplerotic Therapy in Huntington's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Huntington Disease
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
Collaborators: name: Ultragenyx Pharmaceutical Inc
First posted: 2015-05-25
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: volumetric magnetic resonance imaging
timeFrame: 6 months
Secondary outcomes:
measure: motor function after 6 months
timeFrame: 6 months
measure: 31- Phosphorus Magnetic Resonance Spectroscopy
timeFrame: 3 months
measure: Caudal Atrophy
timeFrame: 12 months
measure: motor function after 12 months
timeFrame: 12 months
measure: Patient autonomy after 6 months
timeFrame: 6 months
measure: Patient autonomy after 12 months
timeFrame: 12 months
measure: Sustained restoration of brain energy metabolism after 6 months
timeFrame: 6 months
measure: Sustained restoration of brain energy metabolism after 12 months
timeFrame: 12 months
measure: Symbol Digit Modalities Test after 6 months
timeFrame: 6 months
measure: Symbol Digit Modalities Test after 12 months
timeFrame: 12 months
measure: Stroop test after 6 months
timeFrame: 6 months
measure: Stroop test after 12 months
timeFrame: 12 months
measure: Trail making test after 6 months
timeFrame: 6 months
measure: Trail making test after 12 months
timeFrame: 12 months
measure: Digit span test after 6 months
timeFrame: 6 months
measure: Digit span test after 12 months
timeFrame: 12 months
measure: psychiatric symptoms after 3 months
timeFrame: 3 months
measure: psychiatric symptoms after 6 months
timeFrame: 6 months
measure: psychiatric symptoms after 9 months
timeFrame: 9 months
measure: psychiatric symptoms after 12 months
timeFrame: 12 months
measure: patients' daily life
timeFrame: 6 months
measure: quality of life questionnaire after 6 months
timeFrame: 6 months
measure: quality of life questionnaire after 12 months
timeFrame: 12 months
measure: Number of adverse events
timeFrame: 12 months
measure: clinical exam for Long term tolerance
timeFrame: 12 months
measure: home nurse visits for Long term tolerance
timeFrame: 12 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Département de Génétique
city: Leiden
country: Netherlands
facility: Department of Neurology
Study officials:
References:
citation: Rodrigues FB, Ferreira JJ, Wild EJ. Huntington's Disease Clinical Trials Corner: June 2019. J Huntingtons Dis. 2019;8(3):363-371. doi: 10.3233/JHD-199003.