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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
100
Triheptanoin oil orally administered at 1g/kg/day
Safflower oil orally administered at 1g/kg/day
Département de Génétique
Paris, France
Department of Neurology
Leiden, Netherlands
volumetric magnetic resonance imaging
A decrease in the rate of caudate atrophy, using volumetric MRI
Time frame: 6 months
motor function after 6 months
Decrease in the progression of the UHDRS United Huntington's Disease Rating Scale after 6 months of treatment
Time frame: 6 months
31- Phosphorus Magnetic Resonance Spectroscopy
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
Time frame: 3 months
Caudal Atrophy
Rate of caudate atrophy, using volumetric MRI
Time frame: 12 months
motor function after 12 months
Decrease in the progression of the UHDRS United Huntington's Disease Rating Scale after 12 months of treatment
Time frame: 12 months
Patient autonomy after 6 months
Stability of the Total Functional Capacity (TFC) after 6 months of treatment
Time frame: 6 months
Patient autonomy after 12 months
Stability of the Total Functional Capacity (TFC) after 12 months of treatment
Time frame: 12 months
Sustained restoration of brain energy metabolism after 6 months
Sustained restoration of brain energy metabolism using 31P-MRS after 6 months of treatment
Time frame: 6 months
Sustained restoration of brain energy metabolism after 12 months
Sustained restoration of brain energy metabolism using 31P-MRS after 12 months of treatment
Time frame: 12 months
Symbol Digit Modalities Test after 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
Time frame: 6 months
Symbol Digit Modalities Test after 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
Time frame: 12 months
Stroop test after 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
Time frame: 6 months
Stroop test after 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
Time frame: 12 months
Trail making test after 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
Time frame: 6 months
Trail making test after 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
Time frame: 12 months
Digit span test after 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
Time frame: 6 months
Digit span test after 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
Time frame: 12 months
psychiatric symptoms after 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
Time frame: 3 months
psychiatric symptoms after 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
Time frame: 6 months
psychiatric symptoms after 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
Time frame: 9 months
psychiatric symptoms after 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
Time frame: 12 months
patients' daily life
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).
Time frame: 6 months
quality of life questionnaire after 6 months
A standardized quality of life questionnaire, the Short Form-36 Health Survey, will be used after 6 months
Time frame: 6 months
quality of life questionnaire after 12 months
A standardized quality of life questionnaire, the Short Form-36 Health Survey, will be used after 12 months
Time frame: 12 months
Number of adverse events
Safety of triheptanoin will be evaluated based on review of adverse events
Time frame: 12 months
clinical exam for Long term tolerance
Long-term tolerance will be confirmed by clinical exam at study visits
Time frame: 12 months
home nurse visits for Long term tolerance
Long-term tolerance will be confirmed by patient report during home nurse visits
Time frame: 12 months
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