Natural History Study for DNA Repair Disorders

Recruiting

• Conditions: DNA Repair Disorder; Xeroderma Pigmentosum; Trichothiodystrophy; Cockayne Syndrome
• Interventions: Other: Interval History; Other: Physical Examination; Other: ECAB Assessment; Other: Specimen Sample Collection; Other: Gait Assessment

• Registration Number: NCT05484570
• Lead Sponsor: University of Minnesota

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).

Detailed Description

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.

Study Timeline

• Study First Submitted: 2022-07-12
• Study First Submitted QC: 2022-07-29
• Study First Posted: 2022-08-02
• Study Start: 2022-10-01
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-11
• Last Update Posted: 2024-12-13
• Primary Completion: 2025-08
• Study Completion: 2025-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Diagnosed	ECAB Assessment	Patients who are diagnosed with a DNA Repair Disorder
Control	Specimen Sample Collection	Healthy family members of enrolled diagnosed participants.
Diagnosed	Physical Examination	Patients who are diagnosed with a DNA Repair Disorder
Diagnosed	Gait Assessment	Patients who are diagnosed with a DNA Repair Disorder
Diagnosed	Interval History	Patients who are diagnosed with a DNA Repair Disorder
Diagnosed	Specimen Sample Collection	Patients who are diagnosed with a DNA Repair Disorder
Control	ECAB Assessment	Healthy family members of enrolled diagnosed participants.
Control	Gait Assessment	Healthy family members of enrolled diagnosed participants.

Primary Outcome Measures

Name	Time	Method
Longitudinal stability of cerebellar and gait function on neurological examination	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.
Longitudinal stability of motor function using gait speed measurement	3 years	Longitudinal stability of motor function in study participants as assessed by gait speed measured over a 10 meter distance
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

Trial Locations

Locations (1)

University of Minnesota- Twin Cities; 🇺🇸 Minneapolis, Minnesota, United States