A randomized, controlled, double-blind, crossover trial of triheptanoin in alternating hemiplegia of childhood
Abstract Background Based on the hypothesis of a brain energy deficit, we investigated the safety and efficacy of triheptanoin on paroxysmal episodes in patients with alternating hemiplegia of childhood due to ATP1A3 mutations. Methods We conducted a randomized, double-blind, placebo-controlled cros...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-10-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13023-017-0713-2 |
| _version_ | 1818134334206377984 |
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| author | Elodie Hainque Samantha Caillet Sandrine Leroy Constance Flamand-Roze Isaac Adanyeguh Fanny Charbonnier-Beaupel Maryvonne Retail Benjamin Le Toullec Mariana Atencio Sophie Rivaud-Péchoux Vanessa Brochard Florence Habarou Chris Ottolenghi Florence Cormier Aurélie Méneret Marta Ruiz Mohamed Doulazmi Anne Roubergue Jean-Christophe Corvol Marie Vidailhet Fanny Mochel Emmanuel Roze |
| author_facet | Elodie Hainque Samantha Caillet Sandrine Leroy Constance Flamand-Roze Isaac Adanyeguh Fanny Charbonnier-Beaupel Maryvonne Retail Benjamin Le Toullec Mariana Atencio Sophie Rivaud-Péchoux Vanessa Brochard Florence Habarou Chris Ottolenghi Florence Cormier Aurélie Méneret Marta Ruiz Mohamed Doulazmi Anne Roubergue Jean-Christophe Corvol Marie Vidailhet Fanny Mochel Emmanuel Roze |
| author_sort | Elodie Hainque |
| collection | DOAJ |
| description | Abstract Background Based on the hypothesis of a brain energy deficit, we investigated the safety and efficacy of triheptanoin on paroxysmal episodes in patients with alternating hemiplegia of childhood due to ATP1A3 mutations. Methods We conducted a randomized, double-blind, placebo-controlled crossover study of triheptanoin, at a target dose corresponding to 30% of daily calorie intake, in ten patients with alternating hemiplegia of childhood due to ATP1A3 mutations. Each treatment period consisted of a 12-week fixed-dose phase, separated by a 4-week washout period. The primary outcome was the total number of paroxysmal events. Secondary outcomes included the number of paroxysmal motor-epileptic events; a composite score taking into account the number, severity and duration of paroxysmal events; interictal neurological manifestations; the clinical global impression-improvement scale (CGI-I); and safety parameters. The paired non-parametric Wilcoxon test was used to analyze treatment effects. Results In an intention-to-treat analysis, triheptanoin failed to reduce the total number of paroxysmal events (p = 0.646), including motor-epileptic events (p = 0.585), or the composite score (p = 0.059). CGI-I score did not differ between triheptanoin and placebo periods. Triheptanoin was well tolerated. Conclusions Triheptanoin does not prevent paroxysmal events in Alternating hemiplegia of childhood. We show the feasibility of a randomized placebo-controlled trial in this setting. Trial registration The study has been registered with clinicaltrials.gov ( NCT002408354 ) the 03/24/2015. |
| first_indexed | 2024-12-11T09:06:58Z |
| format | Article |
| id | doaj.art-a99b74495ac847fd9ca2c7591eb1311f |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-11T09:06:58Z |
| publishDate | 2017-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-a99b74495ac847fd9ca2c7591eb1311f2022-12-22T01:13:37ZengBMCOrphanet Journal of Rare Diseases1750-11722017-10-011211710.1186/s13023-017-0713-2A randomized, controlled, double-blind, crossover trial of triheptanoin in alternating hemiplegia of childhoodElodie Hainque0Samantha Caillet1Sandrine Leroy2Constance Flamand-Roze3Isaac Adanyeguh4Fanny Charbonnier-Beaupel5Maryvonne Retail6Benjamin Le Toullec7Mariana Atencio8Sophie Rivaud-Péchoux9Vanessa Brochard10Florence Habarou11Chris Ottolenghi12Florence Cormier13Aurélie Méneret14Marta Ruiz15Mohamed Doulazmi16Anne Roubergue17Jean-Christophe Corvol18Marie Vidailhet19Fanny Mochel20Emmanuel Roze21Université de la Sorbonne, UPMC Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, Institut du Cerveau et de la MoëlleService de Diététique, Hôpital Pitié-Salpêtrière, AP-HPEpiScienceCentre Hospitalier Sud-Francilien, Université Paris Sud, Corbeil-Essonnes, Service de Neurologie et Unité NeurovasculaireUniversité de la Sorbonne, UPMC Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, Institut du Cerveau et de la MoëllePharmacie, Hôpital Pitié-Salpêtrière, AP-HPINSERM, Centre d’Investigation Clinique Neurosciences, CIC-1422, Hôpital Pitié-Salpêtrière, AP-HPINSERM, Centre d’Investigation Clinique Neurosciences, CIC-1422, Hôpital Pitié-Salpêtrière, AP-HPUniversité de la Sorbonne, UPMC Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, Institut du Cerveau et de la MoëlleUniversité de la Sorbonne, UPMC Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, Institut du Cerveau et de la MoëlleINSERM, Centre d’Investigation Clinique Neurosciences, CIC-1422, Hôpital Pitié-Salpêtrière, AP-HPService de Biochimie Métabolomique et protéomique, Hôpital Necker et Université Paris Descartes, AP-HPService de Biochimie Métabolomique et protéomique, Hôpital Necker et Université Paris Descartes, AP-HPUniversité de la Sorbonne, UPMC Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, Institut du Cerveau et de la MoëlleUniversité de la Sorbonne, UPMC Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, Institut du Cerveau et de la MoëlleUniversité de la Sorbonne, UPMC Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, Institut du Cerveau et de la MoëlleSorbonne Universités, UPMC Paris 06, CNRS UMR8256, Institut de Biologie Paris Seine, Adaptation Biologique et vieillissementDépartement de Neurologie, Hôpital Saint-Antoine, AP-HPUniversité de la Sorbonne, UPMC Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, Institut du Cerveau et de la MoëlleUniversité de la Sorbonne, UPMC Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, Institut du Cerveau et de la MoëlleUniversité de la Sorbonne, UPMC Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, Institut du Cerveau et de la MoëlleUniversité de la Sorbonne, UPMC Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, Institut du Cerveau et de la MoëlleAbstract Background Based on the hypothesis of a brain energy deficit, we investigated the safety and efficacy of triheptanoin on paroxysmal episodes in patients with alternating hemiplegia of childhood due to ATP1A3 mutations. Methods We conducted a randomized, double-blind, placebo-controlled crossover study of triheptanoin, at a target dose corresponding to 30% of daily calorie intake, in ten patients with alternating hemiplegia of childhood due to ATP1A3 mutations. Each treatment period consisted of a 12-week fixed-dose phase, separated by a 4-week washout period. The primary outcome was the total number of paroxysmal events. Secondary outcomes included the number of paroxysmal motor-epileptic events; a composite score taking into account the number, severity and duration of paroxysmal events; interictal neurological manifestations; the clinical global impression-improvement scale (CGI-I); and safety parameters. The paired non-parametric Wilcoxon test was used to analyze treatment effects. Results In an intention-to-treat analysis, triheptanoin failed to reduce the total number of paroxysmal events (p = 0.646), including motor-epileptic events (p = 0.585), or the composite score (p = 0.059). CGI-I score did not differ between triheptanoin and placebo periods. Triheptanoin was well tolerated. Conclusions Triheptanoin does not prevent paroxysmal events in Alternating hemiplegia of childhood. We show the feasibility of a randomized placebo-controlled trial in this setting. Trial registration The study has been registered with clinicaltrials.gov ( NCT002408354 ) the 03/24/2015.http://link.springer.com/article/10.1186/s13023-017-0713-2Alternating hemiplegia of childhoodTriheptanoinCrossover trial |
| spellingShingle | Elodie Hainque Samantha Caillet Sandrine Leroy Constance Flamand-Roze Isaac Adanyeguh Fanny Charbonnier-Beaupel Maryvonne Retail Benjamin Le Toullec Mariana Atencio Sophie Rivaud-Péchoux Vanessa Brochard Florence Habarou Chris Ottolenghi Florence Cormier Aurélie Méneret Marta Ruiz Mohamed Doulazmi Anne Roubergue Jean-Christophe Corvol Marie Vidailhet Fanny Mochel Emmanuel Roze A randomized, controlled, double-blind, crossover trial of triheptanoin in alternating hemiplegia of childhood Orphanet Journal of Rare Diseases Alternating hemiplegia of childhood Triheptanoin Crossover trial |
| title | A randomized, controlled, double-blind, crossover trial of triheptanoin in alternating hemiplegia of childhood |
| title_full | A randomized, controlled, double-blind, crossover trial of triheptanoin in alternating hemiplegia of childhood |
| title_fullStr | A randomized, controlled, double-blind, crossover trial of triheptanoin in alternating hemiplegia of childhood |
| title_full_unstemmed | A randomized, controlled, double-blind, crossover trial of triheptanoin in alternating hemiplegia of childhood |
| title_short | A randomized, controlled, double-blind, crossover trial of triheptanoin in alternating hemiplegia of childhood |
| title_sort | randomized controlled double blind crossover trial of triheptanoin in alternating hemiplegia of childhood |
| topic | Alternating hemiplegia of childhood Triheptanoin Crossover trial |
| url | http://link.springer.com/article/10.1186/s13023-017-0713-2 |
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