Clinical trial NCT06273150: Dentatorubral-pallidoluysian Atrophy Natural History and Biomarkers Study
Official title: Dentatorubral-pallidoluysian Atrophy Natural History and Biomarkers Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Dentatorubral-Pallidoluysian Atrophy
Keywords: Dentatorubral-Pallidoluysian Atrophy
Ataxia
Epilepsy
Chorea
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: University of North Carolina, Chapel Hill
name: NYU Langone Health
First posted: 2024-02-22
Enrollment: 225
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Community and/or clinical sample

Brief summary: DRPLA Natural History and Biomarkers Study (DRPLA NHBS) is a prospective observational study that will lay the foundation for clinical trials in DRPLA. The aims of this project are:

* To characterize the natural history of DRPLA in both juvenile- and adult-onset patients and study different modalities of biomarkers in this condition.
* To identify genetic factors and biomarkers that could predict disease progression.
* To provide a platform to support the design and conduct of clinical trials.

This study has three arms:

1. Adult Participants: this arm of the study will require participants to be 16 years old or over to participate.
2. Pediatric Participants: this arm of the study will require participants to be under 16 years old to participate.
3. Remote Participants: patients that cannot or do not wish to travel to one of the study sites can participate in this arm of the study, irrespective of their age.

Participants will have an annual visit for three years (baseline visit and two follow-up visits, three visits in total). Subjects who complete the whole protocol will be assessed on two consecutive days to reduce patient burden.

This project will allow for a better understanding of DRPLA and its course, and therefore allow for future clinical trials on this condition to be more precisely and effectively conducted.


Eligibility criteria: Inclusion criteria for the Adult Protocol:

1. DRPLA adult participants must be 16 years old or over at the time of enrollment, to participate.
2. DRPLA adult participants must have a genetic diagnosis of DRPLA and CAG repeat expansion \>35.
3. Patient is able to read, understand, and provide written informed consent (signed and dated). If the patient is under the age of 18 or is unable to provide consent, the patient must have a parent or caregiver capable of providing informed consent (signed and dated) and able to attend all scheduled study visits, and provide feedback regarding the participant's symptoms and performance as described in the protocol.
4. Adult pre-symptomatic subjects must have a positive genetic test for the DRPLA expansion without symptoms compatible with the disease, and be 16 years old or over at the time of enrollment.
5. Adult Family/Community control participants must be 16 years old or over at the time of enrollment to participate. Blood-relatives must not have a genetic diagnosis of DRPLA or their genetic status is unknown.

Exclusion criteria for the Adult Protocol:

1. Individuals with an ataxia condition other than DRPLA.
2. Failure to sign the consent form will result in study exclusion.
3. Has any condition or circumstance that, in the opinion of the Investigator, makes the participant unsuitable for enrolment. These may include medical conditions which might affect the measurement of biomarkers.
4. Participants will be excluded from the lumbar puncture, and skin biopsy procedures if they have a history of severe allergic or anaphylactic reactions or other adverse reactions to local anesthetics used in the study.
5. For family/community controls: those individuals with neurological conditions (other than primary headache disorders) will be excluded.

Inclusion Criteria for the Pediatric Protocol:

a. DRPLA pediatric participants must be under 16 years old at the time of enrollment, to participate.

f. DRPLA pediatric participants must have a genetic diagnosis of DRPLA and CAG repeat expansion \>35.

g. If the patient is under the age of 18 or is unable to provide consent, the patient must have a parent or caregiver capable of providing informed consent (signed and dated) and able to attend all scheduled study visits, and provide feedback regarding the participant's symptoms and performance as described in the protocol.

h. Pediatric Family/Community control participants must be under 16 years old at the time of enrollment to participate. Blood-relatives must not have a genetic diagnosis of DRPLA or their genetic status is unknown.

Exclusion Criteria for the Pediatric Protocol:

f. Individuals with an ataxia condition other than DRPLA. g. Failure to sign the consent form will result in study exclusion. h. Has any condition or circumstance that, in the opinion of the Investigator, makes the participant unsuitable for enrolment. These may include medical conditions which might affect the measurement of biomarkers.

i. Participants will be excluded from the lumbar puncture, and skin biopsy procedures if they have a history of severe allergic or anaphylactic reactions or other adverse reactions to local anesthetics used in the study.

j. For family/community controls: those individuals with neurological conditions (other than primary headache disorders) will be excluded.

Primary outcomes:
measure: Scale for the assessment and rating of ataxia (SARA)
timeFrame: 3 years
measure: Brain atrophy
timeFrame: 3 years
measure: Neurofilament plasma concentration (NfL)
timeFrame: 3 years
Secondary outcomes:
measure: Inventory of non-ataxia signs (INAS)
timeFrame: 3 years
measure: Upper limb function test AIM-S
timeFrame: 3 years
measure: Redenlab DRPLA specific speech battery
timeFrame: 3 years
measure: Clinical Assessment of Dysphagia in Neurodegeneration (CADN)
timeFrame: 3 years
measure: Tau plasma concentration
timeFrame: 3 years
measure: Glial fibrillary acidic protein (GFAP) concentration
timeFrame: 3 years
measure: Ubiquitin carboxyterminal hydrolase L1 (UCH-L1) concentration
timeFrame: 3 years
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Grossman School of Medicine
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: London
country: United Kingdom
facility: University College London
Study officials:
affiliation: University College, London
name: Paola Giunti
role: PRINCIPAL_INVESTIGATOR
References: