Natural History Study for DNA Repair Disorders

Обзор

This will be a single-center, single-arm, non-interventional natural history study to evaluate the longitudinal clinical course, functional outcome measures, and candidate biomarkers for individuals with DNA repair disorders, including Cockayne syndrome (CS), xeroderma pigmentosum (XP), and trichothiodystrophy (TTD).

Подробное описание

This will be a single-center, single-arm, non-interventional natural history study to evaluate the longitudinal clinical course, functional outcome measures, and candidate biomarkers for individuals with DNA repair disorders, including Cockayne syndrome (CS), xeroderma pigmentosum (XP), and trichothiodystrophy (TTD). Our hypothesis is that a reliable and reproducible baseline natural history course can be established for DNA repair disorders using the Early Childhood Assessment of Balance (ECAB) as a primary endpoint and other measures as secondary and exploratory endpoints that may be used in future therapeutic clinical trials.

Вмешательства

• Другое Interval History
  The study coordinator or another team member will review standard health questions relevant to DNA repair disorders. The control group will not undergo an interval history. These questions will include: 1. How the participant's appetite and general weight trajectory has been since the last assessment 2. Any episodes of unexplained bleeding or bruising 3. Any jaundice 4. General level of alertness and interaction with family and others 5. Any changes in cognitive function such as speech, followi
• Другое Physical Examination
  A board-certified neurologist (the principal investigator) will perform a general physical examination and a neurological examination and complete a standard CRF to document relevant findings. The control group will not undergo a physical examination.
• Другое ECAB Assessment
  An Early Clinical Assessment of Balance (ECAB) will be performed by the physical therapist. Part I can be assessed in all affected individuals, and Part II requires ambulation. For non-ambulatory individuals, only Part I will be applied. The items in the ECAB are summarized as follows: Part I. Head and trunk postural control (maximum 36 points) Head righting - lateral (right and left) Head righting - extension Head righting - flexion Rotation in trunk (right and left) Equilibrium reactions in s
• Другое Gait Assessment
  For ambulatory participants, the physical therapist will also assess standardized gait outcome measures, including: 1. Gait Speed: may be measured over a 10 meter distance, assessing both "comfortable" walking speed and "fast" walking speed 2. 10-meter walk/run: timed assessment at fastest gait attainable. This assessment would be omitted for those participants who are determined to have a high fall risk. 3. Timed Up and Go (TUG): time to stand from a chair, walk 3 meters, go around a cone, and
• Другое Specimen Sample Collection
  Total blood volumes collected at each visit will be limited to 5mL/kg body weight, with a maximum of 18mL. Saliva samples may be obtained if research is taking place where blood samples cannot be drawn or transferred.

Первичные конечные точки

• Longitudinal stability of cerebellar and gait function on neurological examination [Срок оценки: 3 years]
• Longitudinal stability of motor function using gait speed measurement [Срок оценки: 3 years]
• Longitudinal stability of motor function using 10 meter walk/run test [Срок оценки: 3 years]
• Longitudinal stability of motor function using Timed Up and Go (TUG) test [Срок оценки: 3 years]
• Longitudinal stability of motor function using the Dynamic Gait Index (DGI) [Срок оценки: 3 years]

Критерии участия

Критерии включения

• Diagnosis of Cockayne syndrome (CS), xeroderma pigmentosum (XP), or trichothiodystrophy (TTD), based on genetic testing and/or key clinical characteristics l characteristics
• Has one or more of the following neurodevelopmental or neurological complications
• Gross motor delay (non-ambulatory or started walking after age 18 months)
• Language delay (non-verbal or started talking after 18 months)
• Altered muscle tone (hypertonia, dystonia, hypotonia)
• Gait difficulties, including stiff gait, short stride, frequent falls, use of orthotics, use of walker
• Tremors
• Microcephaly
• Is a family member of an individual with the above condition
• No restrictions regarding current ambulatory status
• Minimum age for enrollment eligibility will be 6 months due to fragility of neonates with severe forms of DNA repair disorders and limitations of motor assessment scales in infants younger than 6 months. There will be no maximum age for enrollment eligibility.
• No restrictions regarding gender, race, or ethnicity.
• Voluntary written consent from the participant if adult capable of consenting or parent/guardian if minor or not capable of consenting
• Written consent of Legally Authorized Representative if enrolling adult lacks capacity to consent

Критерии исключения

• Any prior history of systemic gene or cell-based therapy
• Current participation in an interventional clinical trial

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

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• University of Minnesota- Twin Cities — Minneapolis

Идентификаторы

NCT: NCT05484570 · NEUR-2022-30942

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗