Natural History Study for DNA Repair Disorders

NCT05484570 | Recruiting

• 1 other identifier: NEUR-2022-30942
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

DNA Repair Disorder; Cockayne Syndrome; Xeroderma Pigmentosum; Trichothiodystrophy

Outcome Measures

Primary Outcomes (5)

• Longitudinal stability of cerebellar and gait function on neurological examination

  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.

  3 years

• Longitudinal stability of motor function using gait speed measurement

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

  3 years

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

  3 years

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

  3 years

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

  3 years

Other Outcomes (1)

• Exploratory

  3 years

Study Arms (2)

Diagnosed

Patients who are diagnosed with a DNA Repair Disorder

Other: Interval History; Other: Physical Examination; Other: ECAB Assessment; Other: Gait Assessment; Other: Specimen Sample Collection

Control

Healthy family members of enrolled diagnosed participants.

Other: ECAB Assessment; Other: Gait Assessment; Other: Specimen Sample Collection

Interventions

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: 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, following commands, comprehension 6. Any changes in motor function, including the development of tremors and stiffness in movements

Diagnosed

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.

Diagnosed

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

Control; Diagnosed

Gait Assessment OTHER

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 return to the chair (with or without an assistive device) 4. Dynamic Gait Index (DGI): assesses 8 balance challenges while walking

Control; Diagnosed

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.

Control; Diagnosed

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Any person 6 months or older who is either diagnosed with a DNA repair disorder, or has a family member who is diagnosed with a DNA repair disorder

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota- Twin Cities

Minneapolis, Minnesota, 55455, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

1. Comprehensive metabolic panel (CMP) that includes electrolytes, ALT, AST, and LDH. 2. GGT 3. Bilirubin 4. Complete blood count (CBC) 5. Neurofilament light (NfL)40-42 6. Glial fibrillary acidic protein (GFAP)43 7. Total tau (t-tau)44 8. Ubiquitin C-terminal hydrolase (UCHL1)45

MeSH Terms

Conditions

DNA Repair-Deficiency Disorders; Cockayne Syndrome; Xeroderma Pigmentosum; Trichothiodystrophy Syndromes

Interventions

Restraint, Physical

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Precancerous Conditions; Neoplasms; Skin Abnormalities; Skin Diseases, Genetic; Photosensitivity Disorders; Skin Diseases; Skin and Connective Tissue Diseases; Pigmentation Disorders

Intervention Hierarchy (Ancestors)

Behavior Control; Therapeutics; Immobilization; Investigative Techniques

Study Officials

• Peter Kang, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erin Aguero

CONTACT

neurogenetics@umn.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2022
• First Posted: August 2, 2022
• Study Start: October 1, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1)