PRECREST: a phase II prevention and biomarker trial of creatine in at-risk Huntington disease
Rosas HD, Doros G, Gevorkian S, Malarick K, Reuter M, Coutu JP, Triggs TD, Wilkens PJ, Matson W, Salat DH, Hersch SM
Neurology · 73 citas
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- U.S. Food and Drug Administration
- Gobierno
- National Institute of Neurological Disorders and Stroke
- Gobierno
- National Center for Complementary and Integrative Health
- Gobierno
- NCCIH NIH HHS
- Gobierno
- NINDS NIH HHS
- Gobierno
- FDA HHS
- Subvenciones
- National Institute of Neurological Disorders and Stroke (NS042861); National Institute of Neurological Disorders and Stroke (R01NS042861); U.S. Food and Drug Administration (FD003359); National Institute of Neurological Disorders and Stroke (P01NS058793); National Center for Complementary and Integrative Health (AT000613); National Institute of Neurological Disorders and Stroke (NS058793)
Según 6 financiadores declarados.
Publicación
- Publicado
- 2014-02-08 · Neurology · vol. 82 · número 10 · págs. 850–857
- Editorial
- Lippincott Williams & Wilkins
- Citado
- 98 citas · más que el 98% de estudios similares · 7.1× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 25 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Genetic Neurodegenerative Diseases · Parkinson's Disease Mechanisms and Treatments · Lysosomal Storage Disorders Research
- Palabras clave
- Huntington's disease, creatine monohydrate, disease prevention, premanifest Huntington disease, at-risk individuals, safety and tolerability, prodromal biomarkers, neuroimaging, cognitive performance, genetic testing
- MeSH
- brain, humans, huntington disease, atrophy, genetic predisposition to disease, creatine, diffusion magnetic resonance imaging, treatment outcome, feasibility studies, cross-over studies, double-blind method, cognition disorders, time factors, adult, prodromal symptoms, biomarkers
11 autores
- Herminia Diana Rosas🇺🇸Boston University; Edith Nourse Rogers Memorial Veterans Hospital; Harvard–MIT Division of Health Sciences and Technology; Athinoula A. Martinos Center for Biomedical Imaging; Massachusetts Institute of Technology
- Gheorghe D. Doros🇺🇸Boston University; Edith Nourse Rogers Memorial Veterans Hospital; Harvard–MIT Division of Health Sciences and Technology; Athinoula A. Martinos Center for Biomedical Imaging; Massachusetts Institute of Technology
- Sona Gevorkian🇺🇸Boston University; Edith Nourse Rogers Memorial Veterans Hospital; Harvard–MIT Division of Health Sciences and Technology; Athinoula A. Martinos Center for Biomedical Imaging; Massachusetts Institute of Technology
- Keith Malarick🇺🇸Boston University; Edith Nourse Rogers Memorial Veterans Hospital; Harvard–MIT Division of Health Sciences and Technology; Athinoula A. Martinos Center for Biomedical Imaging; Massachusetts Institute of Technology
- Martin Reuter🇺🇸Boston University; Edith Nourse Rogers Memorial Veterans Hospital; Harvard–MIT Division of Health Sciences and Technology; Athinoula A. Martinos Center for Biomedical Imaging; Massachusetts Institute of Technology
- Jean‐Philippe Coutu🇺🇸Boston University; Edith Nourse Rogers Memorial Veterans Hospital; Harvard–MIT Division of Health Sciences and Technology; Athinoula A. Martinos Center for Biomedical Imaging; Massachusetts Institute of Technology
- Tyler D. Triggs🇺🇸Boston University; Edith Nourse Rogers Memorial Veterans Hospital; Harvard–MIT Division of Health Sciences and Technology; Athinoula A. Martinos Center for Biomedical Imaging; Massachusetts Institute of Technology
- Paul J. Wilkens🇺🇸Boston University; Edith Nourse Rogers Memorial Veterans Hospital; Harvard–MIT Division of Health Sciences and Technology; Athinoula A. Martinos Center for Biomedical Imaging; Massachusetts Institute of Technology
- Wayne R. Matson🇺🇸Boston University; Edith Nourse Rogers Memorial Veterans Hospital; Harvard–MIT Division of Health Sciences and Technology; Athinoula A. Martinos Center for Biomedical Imaging; Massachusetts Institute of Technology
- David H. Salat🇺🇸Boston University; Edith Nourse Rogers Memorial Veterans Hospital; Harvard–MIT Division of Health Sciences and Technology; Athinoula A. Martinos Center for Biomedical Imaging; Massachusetts Institute of Technology
- Steven M. Hersch🇺🇸Boston University; Edith Nourse Rogers Memorial Veterans Hospital; Harvard–MIT Division of Health Sciences and Technology; Athinoula A. Martinos Center for Biomedical Imaging; Massachusetts Institute of Technology
Resumen
El texto original del estudio, en el idioma en que se publicó.
Objective
To assess the safety and tolerability of high-dose creatine, the feasibility of enrolling premanifest and 50% at-risk subjects in a prevention trial, and the potential of cognitive, imaging, and blood markers.
Methods
Sixty-four eligible consenting participants were randomly allocated (1:1) to 15 g twice daily of creatine monohydrate or placebo for a 6-month double-blind phase followed by a 12-month open-label extension. Subjects included premanifest (tested) and at-risk (not tested) individuals without clinical symptoms or signs of Huntington disease (HD). Primary outcomes were safety and tolerability. Exploratory endpoints included fine motor, visuospatial, and memory performance; structural and diffusion MRI; and selected blood markers.
Results
Forty-seven HD carriers and 17 non-HD controls were enrolled. Fifteen discontinued treatment (2 assigned to placebo); all were followed for the entire study period. Primary analysis was by intent to treat. The most common adverse events were gastrointestinal. Neuroimaging demonstrated treatment-related slowing of cortical and striatal atrophy at 6 and 18 months.
Conclusion
We describe a design that preserves the autonomy of subjects not wanting genetic testing while including controls for assessing the specificity of treatment effects. Our results demonstrate the feasibility of prevention trials for HD and the safety of high-dose creatine, provide possible evidence of disease modification, support future studies of creatine, and illustrate the value of prodromal biomarkers.
Classification of evidence
This study provides Class I evidence that high-dose creatine is safe and tolerable.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
Confianza de la comunidad
Cargando…
¿Cuánto confías en los hallazgos de este estudio?
Comentarios
¿Algo está mal aquí?
Señala este estudio si su información, etiquetas o financiación parecen incorrectas. Un editor revisa cada señalamiento.
Información educativa sobre investigación publicada. No es consejo médico ni una recomendación para empezar o dejar nada.