OBJECTIVE: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. METHODS: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. RESULTS: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. CONCLUSIONS: These data do not justify use of CoQ as a treatment to slow functional decline in HD. ClinicalTrials.gov identifier: NCT00608881. Classification of evidence: This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD. (PsycINFO Database Record (c) 2017 APA, all rights reserved)
OBJECTIVE: To investigate whether creatine administration could slow progressive functional decline in adults with early symptoms of Huntington disease. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled study of up to 40 g daily of creatine monohydrate in participants with stage I and II HD treated for up to 48 months. The primary outcome measure was the rate of change in total functional capacity (TFC) between baseline and end of follow-up. Secondary outcome measures included changes in additional clinical scores, tolerability, and quality of life. Safety was assessed by adverse events and laboratory studies. RESULTS: At 46 sites in North America, Australia, and New Zealand, 553 participants were randomized to creatine (275) or placebo (278). The trial was designed to enroll 650 patients, but was halted for futility after the first interim analysis. The estimated rates of decline in the primary outcome measure (TFC) were 0.82 points per year for participants on creatine, 0.70 points per year for participants on placebo, favoring placebo (nominal 95% confidence limits −0.11 to 0.35). Adverse events, mainly gastrointestinal, were significantly more common in participants on creatine. Serious adverse events, including deaths, were more frequent in the placebo group. Subgroup analysis suggested that men and women may respond differently to creatine treatment. CONCLUSIONS: Our data do not support the use of creatine treatment for delaying functional decline in early manifest HD. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Importance: Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases activemetabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. OBJECTIVE: To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. Design, Setting and Participants: Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. INTERVENTIONS: Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. Main Outcomes and Measures: Primary end pointwas the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form–physical functioning subscale score (SF-36), and the change in the Berg Balance Test. RESULTS: Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was -2.5 units (95% CI, -3.7 to -1.3) (<i>P</i> < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (<i>P</i> = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (<i>P</i> = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (<i>P</i> = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, -0.3 to 2.3; <i>P</i> = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. Conclusions and Relevance: Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety. (PsycInfo Database Record (c) 2022 APA, all rights reserved)
BACKGROUND: It has been suggested that treatment with ethyl-eicosapentaenoic acid (EPA) may improve motor function in patients with Huntington's disease (HD) with cytosine-adenine-guanine repeat numbers of <45.
METHODS: This multicenter, randomized, double-blind, placebo-controlled 6-month trial compared the effects of ethyl-EPA versus placebo on 290 subjects with mild-to-moderate HD. The primary endpoint was the change from baseline to 6 months in the Total Motor Score 4 (TMS-4) component of the Unified Huntington's Disease Rating Scale (UHDRS). Secondary endpoints included change from baseline in UHDRS subscores and Clinical Global Impression (CGI).
RESULTS: No significant differences in TMS-4 scores were noted between treatment groups. Similarly, there were no significant differences between groups on any of the UHDRS subscores or CGI scores.
CONCLUSION: Ethyl-EPA was not beneficial in patients with HD during 6 months of placebo-controlled evaluation.
ANTECEDENTES: En la enfermedad de Huntington (HD) de los pacientes que reciben tratamiento con rivastigmina mejora de los síntomas conductuales y de la función cognitiva (evaluados con el cribado instrumentos de diagnóstico) se ha informado. El objetivo del presente estudio fue verificar dicha mejora en la función cognitiva de evaluación de la función cognitiva con una batería neuropsicológica detallada que abarca todos los sistemas cognitivos relevantes esperados como deteriorados en la fase temprana de alta definición.
Sujetos y métodos: Dieciocho pacientes (18) HD entraron en el estudio y fueron asignados al azar al grupo de rivastigmina y placebo. Todos los sujetos fueron sometidos a evaluación neuropsicológica al inicio del estudio. Seguimiento de la evaluación neuropsicológica se aplicó después de 6 meses de rivastigmina o tratamiento placebo. Dieciocho (18) controles sanos entraron en el estudio de controlar para el efecto la práctica y se sometieron a la evaluación neuropsicológica al inicio del estudio y después de 6 meses, sin necesidad de tratamiento. La batería neuropsicológica consistió en herramientas de evaluación que son sensibles al deterioro cognitivo se ve en la fase temprana de alta definición: CTMT, SDMT, Stroop (atención e información de control), RFFT, TOL, fluidez verbal (función ejecutiva), CVLT-II, RLCE (aprendizaje y memoria). Efecto de la rivastigmina y posible efecto de la práctica se evaluó utilizando el modelo mixto de ANOVA.
RESULTADOS: Sin efecto estadísticamente significativo del tratamiento con rivastigmina sobre la función cognitiva en los pacientes en HD se detectó. No hubo evidencia de la práctica o placebo efecto.
Conclusiones: La evaluación neuropsicológica detallada no confirmó previamente reportados efecto del tratamiento con rivastigmina sobre la función cognitiva en los pacientes en HD. Las limitaciones de nuestro estudio son, en particular, pequeño tamaño de la muestra y la falta de una sola medida de funcionamiento cognitivo relevante en los pacientes en HD. En lugar de centrarse únicamente en la significación estadística, se propone un estudio de relevancia clínica para aclarar la cuestión de los efectos de rivastigmina en HD.
The primary objective of this study is to assess the efficacy of laquinimod as treatment in participants with HD after 52 weeks using the Unified Huntington\'s Disease Rating Scale Total Motor Score (UHDRS-TMS or TMS).
ANTECEDENTES: El deterioro cognitivo se ha reconocido como un síntoma frecuente en la esclerosis múltiple (EM). Los inhibidores de la colinesterasa (ICE) se emplean para el tratamiento de la enfermedad de Alzheimer, pero hay cierta evidencia de que los ICE también podría ser eficaz en pacientes con EM con déficits cognitivos, particularmente los déficit de la función de memoria.
OBJETIVO: El objetivo de este estudio fue evaluar la eficacia de la función y la seguridad de la rivastigmina ICE en pacientes con EM con déficits cognitivos de la memoria, medida por el cambio desde el inicio de la puntuación total retirada de la prueba selectiva que recuerda (SRT) después de 16 semanas de tratamiento.
MÉTODOS: La eficacia y seguridad de rivastigmina fueron analizados en un 16 semanas de duración, multicéntrico, doble ciego, aleatorizado, controlado con placebo, seguida de una fase de tratamiento abierto de un año opcional. Efectos de rivastigmina y placebo fueron comparados por un análisis de covarianza.
RESULTADOS: En total, 86 pacientes fueron incluidos. Los pacientes que recibieron rivastigmina (n = 43) mostró un aumento no significativo en la puntuación total de rellamada (suma de todas las palabras inmediatamente retirados del mercado durante los seis ensayos) sobre el placebo (n = 38) después de 16 semanas de tratamiento (p = 0,2576). Otras medidas de resultado no aportaron evidencias que respaldan los beneficios de la rivastigmina. El tratamiento con rivastigmina fue bien tolerado.
CONCLUSIONES: Con los resultados de este estudio, sigue siendo necesaria la necesidad de una terapia eficaz en pacientes con EM con deterioro cognitivo. Por lo tanto, no se requiere investigación clínica intensiva y continua para explorar las opciones terapéuticas para los déficits cognitivos en los pacientes con EM.
OBJETIVOS: El objetivo de este estudio fue determinar si la memoria no mejoraría con donepezil en comparación con el placebo en un estudio multicéntrico, doble ciego, ensayo clínico aleatorio (ECA).
MÉTODOS: donepezil 10 mg día y se comparó con el placebo para el tratamiento de trastornos de la memoria. Los criterios de elegibilidad incluyeron: edad 18 a 59 años, la esclerosis múltiple clínicamente definida (MS), y el rendimiento ≤ ½ DE por debajo de las normas publicadas en el Auditorio de prueba de aprendizaje verbal de Rey (RAVLT). Evaluaciones neuropsicológicas se realizaron al inicio del estudio y 24 semanas. Los resultados primarios fueron el cambio en el selectivo Reminding Test (SRT) de la memoria verbal y la impresión de los participantes de la memoria de cambio. Los resultados secundarios incluyeron cambios en otras pruebas neuropsicológicas y la impresión del médico que evalúa el cambio de memoria.
RESULTADOS: Un total de 120 participantes se inscribieron y asignados al azar a cualquiera de donepezilo o placebo. No se encontraron efectos significativos del tratamiento entre los grupos a cada medida de resultado primaria de la memoria o de cualquier resultados cognitivos secundarios. Una tendencia se observó para la impresión del médico de la memoria de cambio a favor de donepezilo (37,7%) frente a placebo (23,7%) (p = 0,097). No hay eventos adversos graves o inesperados atribuidos a la medicación del estudio desarrollado.
CONCLUSIONES: Donepezil no mejoraron la memoria, en comparación con el placebo en ninguno de los resultados primarios de este estudio.
CLASIFICACIÓN DE LA PRUEBA: Este estudio proporciona evidencia de clase I que no apoya la hipótesis de que 10 mg de donepezilo día durante 24 semanas es superior al placebo en la mejora de la cognición, medida por la SRT en personas con EM cuya puntuación RAVLT basal fue 0,5 DE o más debajo de la media.
To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD.
METHODS:
We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach.
RESULTS:
An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study.
CONCLUSIONS:
These data do not justify use of CoQ as a treatment to slow functional decline in HD. ClinicalTrials.gov identifier: NCT00608881. Classification of evidence: This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD. (PsycINFO Database Record (c) 2017 APA, all rights reserved)
