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Идёт набор NCT00668187

A Natural History Study of the Gangliosidoses

— Наблюдательное Tay-Sachs Disease Sandhoff Disease Late Onset Tay-Sachs Disease GM1 Gangliosidosis

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают
Это наблюдательное исследование: исследуемое лечение участникам по протоколу не назначают.
Кому может быть актуально
Состояния в реестре: Tay-Sachs Disease, Sandhoff Disease, Late Onset Tay-Sachs Disease, GM1 Gangliosidosis. Базовые параметры: Без ограничений · Все.
Что важно проверить
Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится
США
Следующий шаг
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Обзор

Hypothesis: To characterize and describe disease progression and heterogeneity of the gangliosidosis diseases. This research study seeks to develop a quantitative method to delineate disease progression for the gangliosidosis diseases (Tay-Sachs disease, Sandhoff disease, and GM1 gangliosidosis) in order to better understand the natural history and heterogeneity of these diseases. Such a quantitative method will also be essential for evaluating any treatments that may become available in the future, such as gene therapy. The data from this study will be necessary to provide end-points for future therapies, guide medical decisions about treatment, provide objective measurement of treatment outcomes, and accurately inform parents regarding potential outcomes.

Подробное описание

The infantile form of GM2 and GM1 gangliosidosis diseases ("classic" infantile) is the most common. Infants with Tay-Sachs disease, Sandhoff disease or GM1 gangliosidosis appear normal at birth, but at approximately 6-10 months of age begin to manifest progressive weakness and loss of muscle strength, such as loss of the ability to sit up or turn over. They may evidence deafness, and display decreased attentiveness. This is followed by rapid deterioration of motor skills and slowed mental development (neurodegeneration), often with seizures. Retinal involvement leads to visual impairment and eventual blindness. Death typically occurs by the age of five. Currently there is no treatment for Tay-Sachs disease, Sandhoff disease or GM1 gangliosidosis.

Late Onset Tay-Sachs disease ("LOTS") occurs in patients beginning in their twenties or thirties, and is characterized by poor motor coordination and psychotic behaviors. Patients with LOTS also have decreased life expectancy, although to a lesser degree than those with infantile or juvenile Tay-Sachs or Sandhoff diseases. Currently there is no treatment for LOTS.

This study is comprised of two different 'arms.' The first arm, entitled Aim 1, will focus on the developmental course of infantile and juvenile Tay-Sachs disease, Sandhoff disease, and GM1 gangliosidosis. Longitudinal data from individuals with these diseases will be collected in order to delineate the natural history of these diseases. This data will help to objectify disease progression, and can be used to create a disease stage and severity index.

The second arm, entitled Aim 2, will focus on LOTS and will seek to understand the progression of central nervous system disease, with special focus upon cerebellar and frontal systems. This will be accomplished by using quantitative methods including neuroimaging and neuropsychological measures that explore motor and executive functions, visual-spatial and emotional-behavioral dysfunction.

Первичные конечные точки

  • Change in Child Developmental Status as Assessed by Neuropsychological Tests [Срок оценки: Upon enrollment; then at 12, 24, 36, 48 and 60 months]
Вторичные конечные точки (9)
  • Ascertainment of Enzyme Activity Levels [Срок оценки: Upon enrollment]
  • Medication Regime [Срок оценки: Upon enrollment; then at 12, 24, 36, 48 and 60 months]
  • Clinical Assessments [Срок оценки: Upon enrollment; then at 12, 24, 36, 48 and 60 months]
  • Changes in Child Brain Structure Development and Status, as Assessed by Magnetic Resonance Imaging (MRI) Examination [Срок оценки: Upon enrollment; then at 12, 24, 36, 48 and 60 months]
  • Identification of Genetic Mutation(s) [Срок оценки: Upon Enrollment]
  • Changes in Chitotriosidase Enzyme Activity Levels [Срок оценки: Upon enrollment; then at 12, 24, 36, 48 and 60 months]
  • Ascertainment of Ganglioside Levels [Срок оценки: Upon enrollment]
  • Change in Adult Neurocognitive Status as Assessed by Neuropsychological Tests [Срок оценки: Upon enrollment; then at 12, 24, 36, 48 and 60 months]
  • Changes in Adult Brain Structure Status, as Assessed by Magnetic Resonance Imaging (MRI) Examination [Срок оценки: Upon enrollment; then at 12, 24, 36, 48 and 60 months]

Критерии участия

Критерии включения

  • Subjects must have a documented gangliosidosis disease.
  • Subjects must be able to complete appropriate neuropsychological and neurobehavioral assessments.
  • Late-onset gangliosidosis subjects must be able to tolerate a head MRI.

Критерии исключения

1\. There are no exclusion criteria, beyond a desire not to participate.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения
Когортное

Центры проведения

США · 1 центр
  • University of Minnesota - Pediatric Genetics and Metabolism — Minneapolis

Публикации

  • Toro C, Shirvan L, Tifft C. HEXA Disorders. 1999 Mar 11 [updated 2020 Oct 1]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1218/ PMID 20301397
  • Kaback M, Lim-Steele J, Dabholkar D, Brown D, Levy N, Zeiger K. Tay-Sachs disease--carrier screening, prenatal diagnosis, and the molecular era. An international perspective, 1970 to 1993. The International TSD Data Collection Network. JAMA. 1993 Nov 17;270(19):2307-15. PMID 8230592
  • Neudorfer O, Pastores GM, Zeng BJ, Gianutsos J, Zaroff CM, Kolodny EH. Late-onset Tay-Sachs disease: phenotypic characterization and genotypic correlations in 21 affected patients. Genet Med. 2005 Feb;7(2):119-23. doi: 10.1097/01.gim.0000154300.84107.75. PMID 15714079
  • MacQueen GM, Rosebush PI, Mazurek MF. Neuropsychiatric aspects of the adult variant of Tay-Sachs disease. J Neuropsychiatry Clin Neurosci. 1998 Winter;10(1):10-9. doi: 10.1176/jnp.10.1.10. PMID 9547461
  • Frey LC, Ringel SP, Filley CM. The natural history of cognitive dysfunction in late-onset GM2 gangliosidosis. Arch Neurol. 2005 Jun;62(6):989-94. doi: 10.1001/archneur.62.6.989. PMID 15956171
  • Navon R, Argov Z, Frisch A. Hexosaminidase A deficiency in adults. Am J Med Genet. 1986 May;24(1):179-96. doi: 10.1002/ajmg.1320240123. PMID 2939718
  • Zaroff CM, Neudorfer O, Morrison C, Pastores GM, Rubin H, Kolodny EH. Neuropsychological assessment of patients with late onset GM2 gangliosidosis. Neurology. 2004 Jun 22;62(12):2283-6. doi: 10.1212/01.wnl.0000130498.19019.02. PMID 15210895
  • Utz JR, Crutcher T, Schneider J, Sorgen P, Whitley CB. Biomarkers of central nervous system inflammation in infantile and juvenile gangliosidoses. Mol Genet Metab. 2015 Feb;114(2):274-80. doi: 10.1016/j.ymgme.2014.11.015. Epub 2014 Dec 6. PMID 25557439

Идентификаторы

NCT: NCT00668187 · 0801M24964 · U54NS065768

Первоисточники (государственные реестры)

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