Natural History Study of Patients with HPDL Mutations | NCT05848271

Studies
Natural History Study of Patients with HPDL Mutations

NCT05848271

Sponsor

University of California, San Diego

Status

Recruiting

Last Update Posted

Mar 30, 2025Actual

Enrollment

50Estimated

Phase

Not provided

Conditions

Mitochondrial Encephalomyopathies
Hereditary Spastic Paraplegia
Spastic Paraplegia
White Matter Disease
Neonatal Encephalopathy
Mutation
Genetic Disease

Interventions

Patient Registry
Dry blood spots sampling

Countries

United States

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

Status Module

Record Verification Date

Mar 2025

Overall Recruitment Status or Expanded Access Status

Recruiting

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

May 18, 2023Actual

Primary Completion Date

Dec 31, 2026Estimated

Completion Date

Dec 31, 2027Estimated

First Submitted Date

Apr 28, 2023

First Submission Date that Met QC Criteria

Apr 28, 2023

First Posted Date

May 8, 2023Actual

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Mar 25, 2025

Last Update Posted Date

Mar 30, 2025Actual

Sponsor/Collaborators Module

Responsible Party, by Official Title

Joseph Gleeson, professor, neuroscience, University of California, San DiegoPrincipal Investigator

Lead Sponsor

University of California, San DiegoOTHER

Collaborators

Name	Class
New York University	OTHER
Universität Tübingen	OTHER
Heinrich-Heine University, Duesseldorf	OTHER

Oversight Module

Has Data Monitoring Committee (DMC)

Is FDA Regulated Drug

Is FDA Regulated Device

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

FDAAA801 Violation

Not provided

Description Module

Brief Summary

This study uses medical records that allow retrospective data extraction of clinical manifestation to assess the natural history of HPDL mutations

Detailed Description

A novel mitochondrial disease arises from mutations in HPDL, which codes for 4-hydroxyphenylpyruvate dioxygenase-like protein. The main purpose of this study is to establish a patient registry to gather medical data from consenting HPDL mutation patients worldwide. From longitudinal data, we will be able to figure out the natural history of the disease, and genotype-phenotype correlation. Dry blood spots will be collected to develop biomarkers to understand the disease better.

Conditions Module

Conditions

Mitochondrial Encephalomyopathies
Hereditary Spastic Paraplegia
Spastic Paraplegia
White Matter Disease
Neonatal Encephalopathy
Mutation
Genetic Disease

Keywords

HPDL
HPDL related neonatal mitochondrial encephalopathy
HPDL related hereditary spastic paraplegia
Spastic paraplegia-83
Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities

Design Module

Study Type

Observational

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Target Follow-Up Duration

Not provided

Phases

Not provided

Interventional Study Design

Allocation

Not provided

Intervention Model

Biospecimen

Retention

Enrollment

50Estimated

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
HPDL deficiency		Patients with HPDL mutations	Other: Patient Registry Other: Dry blood spots sampling

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Patient Registry	Other	Participants who have been diagnosed with HPDL mutations will be enrolled to patient registry.	HPDL deficiency

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Clinician questionnaire	Clinician-reported clinical and genetic confirmation of HPDL mutations	12 months

Secondary Outcomes

Not provided

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Any individuals diagnosed with HPDL variants
Clinical diagnosis can include:
- HPDL-related hereditary spastic paraplegia (HSP)
- HPDL-related neonatal mitochondrial encephalopathy
- Spastic paraplegia -83 (SPG83)
- Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA)

Exclusion Criteria:

Any known genetic abnormality (other than HPDL mutation)
Any condition that, in the opinion of the Site Investigator, could put the participant at undue risk and/or would ultimately prevent the completion of study procedures

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

Not provided

Maximum Age

Not provided

Standard Ages

ChildAdultOlder Adult

Study Population

The gene HPDL has been linked to an infantile neurodegenerative condition. The affected patients have various clinical manifestations from spastic paraplegia to NEDSWMA. Severely affected patients exhibit developmental delay, seizures, and spasticity, and can lead to death.

Sampling Method

Non-Probability Sample

Contacts/Locations Module

Central Contacts

Name	Role	Phone	Extension	Email
Eun Hae Lee	Contact	8582460547		gleesonlab@health.ucsd.edu

Overall Officials

Name	Affiliation	Role
Joseph Gleeson	UCSD	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Eun Hae Lee	Recruiting	San Diego	California	92093	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
33188300	Background	Ghosh SG, Lee S, Fabunan R, Chai G, Zaki MS, Abdel-Salam G, Sultan T, Ben-Omran T, Alvi JR, McEvoy-Venneri J, Stanley V, Patel A, Ross D, Ding J, Jain M, Pan D, Lubbert P, Kammerer B, Wiedemann N, Verhoeven-Duif NM, Jans JJ, Murphy D, Toosi MB, Ashrafzadeh F, Imannezhad S, Karimiani EG, Ibrahim K, Waters ER, Maroofian R, Gleeson JG. Biallelic variants in HPDL, encoding 4-hydroxyphenylpyruvate dioxygenase-like protein, lead to an infantile neurodegenerative condition. Genet Med. 2021 Mar;23(3):524-533. doi: 10.1038/s41436-020-01010-y. Epub 2020 Nov 14.
34471290

ID	Term
D017237	Mitochondrial Encephalomyopathies
D015419	Spastic Paraplegia, Hereditary
D010264	Paraplegia
D056784	Leukoencephalopathies
D030342	Genetic Diseases, Inborn

ID	Term
D017240	Mitochondrial Myopathies
D009135	Muscular Diseases
D009140	Musculoskeletal Diseases
D001928	Brain Diseases, Metabolic