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NCT Number: NCT05484570

Natural History Study for DNA Repair Disorders

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).

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Key information

Conditions

DNA Repair Disorder Abnormalities, Multiple Bone Diseases Bone Diseases, Developmental Cockayne Syndrome Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities DNA Repair-Deficiency Disorders Dwarfism Genetic Diseases, Inborn Heredodegenerative Disorders, Nervous System Metabolic Diseases Musculoskeletal Diseases Neoplasms Nervous System Diseases Neurodegenerative Diseases Nutritional and Metabolic Diseases Photosensitivity Disorders Pigmentation Disorders Precancerous Conditions Skin Abnormalities Skin Diseases Skin Diseases, Genetic Skin and Connective Tissue Diseases Trichothiodystrophy Trichothiodystrophy Syndromes Xeroderma Pigmentosum

Age range

6 month and older

Sex eligibility

All sexes

Study type

Observational

Primary location

About this study

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.

Who can participate

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

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

Treatment and study plan

Interval History

Other

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:

  • How the participant's appetite and general weight trajectory has been since the last assessment
  • Any episodes of unexplained bleeding or bruising
  • Any jaundice
  • General level of alertness and interaction with family and others
  • Any changes in cognitive function such as speech, following commands, comprehension
  • Any changes in motor function, including the development of tremors and stiffness in movements

physical examination

Other

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.

ECAB Assessment

Other

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 sitting (right and left) Protective extension - side Protection extension - backward Part II. Sitting and standing postural control (maximum 64 points) Sitting with back unsupported but feet supported on floor or on a stool Sitting to standing Standing unsupported with eyes closed Standing unsupported with feet together Turns 360 degrees Placing alternate foot on the step while standing unsupported

Gait assessment

Other

For ambulatory participants, the physical therapist will also assess standardized gait outcome measures, including:

  • Gait Speed: may be measured over a 10 meter distance, assessing both "comfortable" walking speed and "fast" walking speed
  • 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.
  • Timed Up and Go (TUG): time to stand from a chair, walk 3 meters, go around a cone, and return to the chair (with or without an assistive device)
  • Dynamic Gait Index (DGI): assesses 8 balance challenges while walking

Specimen Sample Collection

Other

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.

Primary outcomes

  1. Longitudinal stability of cerebellar and gait function on neurological examination

    Time frame: 3 years

    The longitudinal stability of cerebellar and gait function will be assessed by the presence or absence of tremors (absence = 1, presence = 0), dysmetria (absence = 1, presence = 0), dysdiadochokinesia (absence = 1, presence = 0) and Gowers sign (absence = 1, presence = 0). The scores will be added to yield a total score ranging from 0 to 4, with 4 representing the best performance.

  2. Longitudinal stability of motor function using gait speed measurement

    Time frame: 3 years

    Longitudinal stability of motor function in study participants as assessed by gait speed measured over a 10 meter distance

  3. Longitudinal stability of motor function using 10 meter walk/run test

    Time frame: 3 years

  4. Longitudinal stability of motor function using Timed Up and Go (TUG) test

    Time frame: 3 years

  5. Longitudinal stability of motor function using the Dynamic Gait Index (DGI)

    Time frame: 3 years

Other outcomes

  1. Exploratory

    Time frame: 3 years

    We have selected the following 4 biomarkers to be measured in serum samples at each study visit:

    • Neurofilament light (NfL)
    • Glial fibrillary acidic protein (GFAP)
    • Total tau (t-tau)
    • Ubiquitin C-terminal hydrolase (UCHL1)

    We have selected the following 4 biomarkers to be measured in serum samples at each study visit:

    • Neurofilament light (NfL)40-42
    • Glial fibrillary acidic protein (GFAP)43
    • Total tau (t-tau)44
    • Ubiquitin C-terminal hydrolase (UCHL1)45 To determine whether a serum biomarker can track disease status and progression and serve as a secondary outcome measure. To determine genetic diagnoses for those who are genetically undiagnosed, and to use transcriptomic analyses to seek additional biomarker candidates.

Study contacts

Contact information is provided by the study sponsor or research team.

Seth Stafki

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

University of Minnesota

Other

Registry information

Important dates

Study start
2022
Primary completion
2026
Study completion
2026
First posted
Aug 2, 2022
Registry last updated
May 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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