Dentatorubral-pallidoluysian Atrophy Natural History and Biomarkers Study

NCT06273150 | Recruiting

• 1 other identifier: 142048
• Study Type: observational
• Target: 225
• Locations: 2 countries
• Sites: 3

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:
• Adult Participants: this arm of the study will require participants to be 16 years old or over to participate.
• Pediatric Participants: this arm of the study will require participants to be under 16 years old to participate.
• 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.

Conditions

Dentatorubral-Pallidoluysian Atrophy

Keywords

Dentatorubral-Pallidoluysian Atrophy; Ataxia; Epilepsy; Chorea

Outcome Measures

Primary Outcomes (3)

• Scale for the assessment and rating of ataxia (SARA)

  Progression of ataxia is measured using a validated ataxia scale, SARA. Scores range from 0 (no ataxia) to 40 (most severe ataxia).

  3 years

• Brain atrophy

  Brain MRI is used to measure atrophy. Atrophy is expected to be observed in DRPLA patients, and in particular in the brainstem, superior cerebellar peduncle, cerebellum and thalamus.

  3 years

• Neurofilament plasma concentration (NfL)

  Blood and CSF samples will be measured for NfL, a brain-derived protein.

  3 years

Secondary Outcomes (7)

• Inventory of non-ataxia signs (INAS)

  3 years

• Upper limb function test AIM-S

  3 years

• Redenlab DRPLA specific speech battery

  3 years

• Clinical Assessment of Dysphagia in Neurodegeneration (CADN)

  3 years

• Tau plasma concentration

  3 years

Study Arms (2)

DRPLA-mutation carrier

Subjects with a positive genetic test for a pathological expansion in the ATN1 gene.

Other: Positive genetic test for pathological expansion in ATN1

Volunteer control

Subjects without neurological conditions (other than primary headache disorders), without a family history of DRPLA or a previous negative genetic test for pathological expansions in the ATN1 gene.

Other: Positive genetic test for pathological expansion in ATN1

Interventions

Positive genetic test for pathological expansion in ATN1 OTHER

Positive genetic test for pathological expansion in ATN1

DRPLA-mutation carrier; Volunteer control

Eligibility Criteria

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

Study Population

Community and/or clinical sample

You may qualify if:

• DRPLA adult participants must be 16 years old or over at the time of enrollment, to participate.
• DRPLA adult participants must have a genetic diagnosis of DRPLA and CAG repeat expansion \>35.
• 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.
• 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.
• 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.

You may not qualify if:

• Individuals with an ataxia condition other than DRPLA.
• 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.
• 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.
• For family/community controls: those individuals with neurological conditions (other than primary headache disorders) will be excluded.
• 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.
• 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.

Sponsors & Collaborators

• University College, London: lead
• University of North Carolina, Chapel Hill: collaborator
• NYU Langone Health: collaborator

Study Sites (3)

NYU Grossman School of Medicine

New York, New York, 10017, United States

RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7025, United States

RECRUITING

University College London

London, WC1N 3BG, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, serum, plasma, CSF, saliva, urine, faeces, and fibroblasts

MeSH Terms

Conditions

Myoclonic Epilepsies, Progressive; Ataxia; Epilepsy; Chorea

Condition Hierarchy (Ancestors)

Epilepsies, Myoclonic; Epilepsy, Generalized; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Movement Disorders

Study Officials

• Paola Giunti

  University College, London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paola Giunti

CONTACT

+44 7899974923; p.giunti@ucl.ac.uk

Hector Garcia-Moreno

CONTACT

h.garcia-moreno@ucl.ac.uk

Study Design

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

Study Record Dates

• First Submitted: February 15, 2024
• First Posted: February 22, 2024
• Study Start: May 1, 2022
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: May 10, 2024

Record last verified: 2024-05

Locations

US (2); GB (1)