Natural History Study for DNA Repair Disorders
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age6+
SponsorUniversity of Minnesota
About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
Any prior history of systemic gene or cell-based therapy
Current participation in an interventional clinical trial
Trial 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
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Interval History
Other interventionThe 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
Physical Examination
Other interventionA 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 interventionAn 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 interventionFor 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
Specimen Sample Collection
Other interventionTotal 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.
Treatment groups
40 Participants
are divided into 2 treatment groupsGroup A: Diagnosed5 interventions
Group B: Control3 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
3 years2
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
Time frame
3 years3
Longitudinal stability of motor function using 10 meter walk/run test
Time frame
3 years4
Longitudinal stability of motor function using Timed Up and Go (TUG) test
Time frame
3 yearsOther outcomes
1
Exploratory
We have selected the following 4 biomarkers to be measured in serum samples at each study visit: 1. Neurofilament light (NfL) 2. Glial fibrillary acidic protein (GFAP) 3. Total tau (t-tau) 4. Ubiquitin C-terminal hydrolase (UCHL1) We have selected the following 4 biomarkers to be measured in serum samples at each study visit: 1. Neurofilament light (NfL)40-42 2. Glial fibrillary acidic protein (GFAP)43 3. Total tau (t-tau)44 4. 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.
Time frame
3 yearsSponsors and contacts
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Source ClinicalTrials.gov