A Comparative Phase 2 Study Assessing the Efficacy of Triheptanoin, an Anaplerotic Therapy in Huntington's Disease
- Registration Number
- NCT02453061
- Lead Sponsor
- Institut National de la Santé Et de la Recherche Médicale, France
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 100
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo group Placebo Subjects will receive safflower oil at 1g/kg/day for 6 months (months 0 - 6) and triheptanoin oil at 1g/kg/day for 6 months (months 7 - 12) Triheptanoin group Triheptanoin oil Subjects will receive triheptanoin oil at 1g/kg/day for 6 months (months 0 - 6) and triheptanoin oil at 1g/kg/day for 6 months (months 7 - 12)
- Primary Outcome Measures
Name Time Method volumetric magnetic resonance imaging 6 months A decrease in the rate of caudate atrophy, using volumetric MRI
- Secondary Outcome Measures
Name Time Method 31- Phosphorus Magnetic Resonance Spectroscopy 3 months An increase in the index of brain energy restoration - as defined by the difference between Pi/PCr ration during visual stimulation and the mean of the Pi/PCr ratio during rest and recovery - using 31P-MRS
Patient autonomy after 6 months 6 months Stability of the Total Functional Capacity (TFC) after 6 months of treatment
Sustained restoration of brain energy metabolism after 12 months 12 months Sustained restoration of brain energy metabolism using 31P-MRS after 12 months of treatment
Caudal Atrophy 12 months Rate of caudate atrophy, using volumetric MRI
Patient autonomy after 12 months 12 months Stability of the Total Functional Capacity (TFC) after 12 months of treatment
Sustained restoration of brain energy metabolism after 6 months 6 months Sustained restoration of brain energy metabolism using 31P-MRS after 6 months of treatment
Trail making test after 12 months 12 months The benefit of triheptanoin on cognitive function will be evaluated after 12 months using a neuropsychological battery including the Trail making test, a test to evaluate mental flexibility
Digit span test after 6 months 6 months The benefit of triheptanoin on cognitive function will be evaluated after 6 months using a neuropsychological battery including the Digit span test, a test evaluating attention and working memory
motor function after 6 months 6 months Decrease in the progression of the UHDRS United Huntington's Disease Rating Scale after 6 months of treatment
motor function after 12 months 12 months Decrease in the progression of the UHDRS United Huntington's Disease Rating Scale after 12 months of treatment
Symbol Digit Modalities Test after 6 months 6 months The benefit of triheptanoin on cognitive function will be evaluated after 6 months using a neuropsychological battery including the SDMT (Symbol Digit Modalities Test), a test of visuomotor coordination
Digit span test after 12 months 12 months The benefit of triheptanoin on cognitive function will be evaluated after 12 months using a neuropsychological battery including the Digit span test, a test evaluating attention and working memory
patients' daily life 6 months The global impact of triheptanoin on patients' daily life will be evaluated at the end of the blinded treatment period using qualitative research methods. To statistically test whether experts classify treated and not treated patients better than could be expected by chance, a permutation test based on a modified version of Fisher's Lady tasting tea procedure will be used (Fischer 1935).
quality of life questionnaire after 6 months 6 months A standardized quality of life questionnaire, the Short Form-36 Health Survey, will be used after 6 months
quality of life questionnaire after 12 months 12 months A standardized quality of life questionnaire, the Short Form-36 Health Survey, will be used after 12 months
Symbol Digit Modalities Test after 12 months 12 months The benefit of triheptanoin on cognitive function will be evaluated after 12 months using a neuropsychological battery including the SDMT (Symbol Digit Modalities Test), a test of visuomotor coordination
Stroop test after 6 months 6 months The benefit of triheptanoin on cognitive function will be evaluated after 6 months using a neuropsychological battery including the Stroop test, a test evaluating concentration and capacity for inhibition
Trail making test after 6 months 6 months The benefit of triheptanoin on cognitive function will be evaluated after 6 months using a neuropsychological battery including the Trail making test, a test to evaluate mental flexibility
Stroop test after 12 months 12 months The benefit of triheptanoin on cognitive function will be evaluated after 12 months using a neuropsychological battery including the Stroop test, a test evaluating concentration and capacity for inhibition
psychiatric symptoms after 3 months 3 months The effect of triheptanoin on psychiatric symptoms will be evaluated after 3 months with the PBA-S, an evaluation of problem behaviors associated with HD
psychiatric symptoms after 6 months 6 months The effect of triheptanoin on psychiatric symptoms will be evaluated after 6 months with the PBA-S, an evaluation of problem behaviors associated with HD
psychiatric symptoms after 9 months 9 months The effect of triheptanoin on psychiatric symptoms will be evaluated after 9 months with the PBA-S, an evaluation of problem behaviors associated with HD
psychiatric symptoms after 12 months 12 months The effect of triheptanoin on psychiatric symptoms will be evaluated after 12 months with the PBA-S, an evaluation of problem behaviors associated with HD
Number of adverse events 12 months Safety of triheptanoin will be evaluated based on review of adverse events
clinical exam for Long term tolerance 12 months Long-term tolerance will be confirmed by clinical exam at study visits
home nurse visits for Long term tolerance 12 months Long-term tolerance will be confirmed by patient report during home nurse visits
Trial Locations
- Locations (2)
Département de Génétique
🇫🇷Paris, France
Department of Neurology
🇳🇱Leiden, Netherlands