RT Journal Article
SR Electronic
T1 J01 Triheptanoin is associated with clinical stability and decreased caudate atrophy in huntington disease
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP A53
OP A53
DO 10.1136/jnnp-2021-EHDN.128
VO 92
IS Suppl 1
A1 Fanny Mochel
A1 Aurélie Meneret
A1 Isaac Adanyeguh
A1 Camille Giron
A1 Elodie Hainque
A1 Marie-Pierre Luton
A1 Marie-Pierre Luton
A1 Mariana Atencio
A1 Milou Jacobs
A1 Fleur Veldkamp
A1 Emma Coppen
A1 Kasper van der Zwaan
A1 Eric Vicaut
A1 Raymund AC Roos
A1 Alexandra Durr
YR 2021
UL http://jnnp.bmj.com/content/92/Suppl_1/A53.1.abstract
AB Objective To assess the efficacy of triheptanoin, a medium chain triglyceride with an odd number of carbons that targets the Krebs cycle, on key brain imaging and clinical measures in HD.Background We previously showed that energy deficit in HD is associated with increased substrate requirements for the Krebs cycle. Using brain MR spectroscopy, we then demonstrated that triheptanoin can restore a normal brain energetic profile in HD patients.Methods We conducted a 6-month randomized controlled bi-centric trial (Paris and Leiden) called TRIHEP3 (NCT02453061), comparing triheptanoin 1g/kg/day vs placebo in 100 patients (ratio 1/1) at an early stage of HD, followed by a 6-month open label phase. Patients could then opt for a one-year extension study. To compare triheptanoin versus placebo over one year, we used the placebo arm of a one-year randomized controlled trial (NCT02336633), conducted in parallel with identical methods, in HD patients with similar clinical characteristics (age, UHDRS-TMS, CAG).Results 86 patients completed the one-year TRIHEP3 study and 42 completed the consecutive 12-month extension. Triheptanoin was well tolerated. We saw no difference in cBSI at 6 months between triheptanoin and placebo. TMS at 12 months tended to stabilize in patients treated with triheptanoin for one year (mean 0.6 ± 5.1) compared to patients treated for 6 months (2.5 ± 4.5) (p= 0.072), with a significant difference between 6 and 12 months (-0.7 ± 3.9 vs 1.9 ± 4.7, p= 0.024). Diffusion tensor imaging showed improved fiber trophicity at 24 months in both groups. Compared to the external placebo control group, at one year, TMS confirmed clinical stability in patients treated with triheptanoin (2.6 ± 4.6 vs 0.6 ± 5.1, p= 0.057) and caudate atrophy was significantly less (-3% vs -6.7% compared to baseline, p< 0.001) (figure 1).Abstract J01 Figure 1 Conclusion These results showed that treatment with triheptanoin was associated with clinical stability and decreased caudate atrophy in HD.