Mitochondrial EncephalomyopathiesNCT05848271
Natural History Study of Patients with HPDL Mutations
An observational study of Mitochondrial Encephalomyopathies and Hereditary Spastic Paraplegia, run by University of California, San Diego at 1 site in United States.
Trial summary
This study uses medical records that allow retrospective data extraction of clinical manifestation to assess the natural history of HPDL mutations Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Mitochondrial Encephalomyopathies, Hereditary Spastic Paraplegia, Spastic Paraplegia
- What is being tested?
- Patient Registry and Dry blood spots sampling
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 18 May 2023to 31 Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older 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.
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Eun Hae Lee
San Diego, California, 92093
Eun Hae Lee, 8582460547, leeeh80@gmail.com
About this study
Official title: A Patient Registry and Natural History Study of Patients with Biallelic HPDL Mutations
This study uses medical records that allow retrospective data extraction of clinical manifestation to assess the natural history of HPDL mutations
Read the 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
- Mitochondrial Encephalomyopathies, Hereditary Spastic Paraplegia, Spastic Paraplegia, White Matter Disease, Neonatal Encephalopathy, Mutation
- Being tested
- Patient Registry, Dry blood spots sampling
- 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
- Medical subject headings
- Mitochondrial Encephalomyopathies, Spastic Paraplegia, Hereditary, Paraplegia, Leukoencephalopathies, Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Patient RegistryOther
Participants who have been diagnosed with HPDL mutations will be enrolled to patient registry.
Dry blood spots samplingOther
Dry blood splots require 500nl of blood.
| Study group | Role | What they receive |
|---|---|---|
| HPDL deficiency | Patients with HPDL mutations Receives: Other: Patient Registry; Other: Dry blood spots sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinician questionnaire
Clinician-reported clinical and genetic confirmation of HPDL mutations
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2023
- Study start18 May 2023
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Mitochondrial EncephalomyopathiesStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- New York University, Universität Tübingen, Heinrich-Heine University, Duesseldorf
- Responsible party
- Principal investigator, Joseph Gleeson, University of California, San Diego
- Investigators
- Joseph Gleeson, Principal investigator, UCSD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05848271
- Sponsor's protocol ID
- HPDL_NHS_001
- Status last verified
- Mar 2025
- First submitted
- 28 Apr 2023
- Last updated
- 30 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33188300Banh RS, Kim ES, Spillier Q, Biancur DE, Yamamoto K, Sohn ASW, Shi G, Jones DR, Kimmelman AC, Pacold ME. The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway. Nature. 2021 Sep;597(7876):420-425. doi: 10.1038/s41586-021-03865-w. Epub 2021 Sep 1.
PubMed 34471290Lee EH, Kim-Mcmanus O, Yang JH, Haas R, Zaki MS, Abdel-Salam GMH, Nakamura Y, Abdel-Hamind MS, Ebrahimi-Fakhari D, Alecu JE, Brunetti-Pierri N, Srinivasan VM, Gowda VK, Gross S, Alanay Y, Najarzadeh Totbati P, Yadavilli M, Friedman L, Ojeda NM, Gleeson JG. HPDL Variant Type Correlates With Clinical Disease Onset and Severity. Ann Clin Transl Neurol. 2025 Jul;12(7):1360-1367. doi: 10.1002/acn3.70047. Epub 2025 May 14.
PubMed 40368591
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Patient Registry and Natural History Study of Patients with Biallelic HPDL Mutations
- ClinicalTrials.gov ID
- NCT05848271
- Acronym / sponsor ID
- HPDL_NHS_001
- Conditions
- Mitochondrial Encephalomyopathies, Hereditary Spastic Paraplegia, Spastic Paraplegia, White Matter Disease, Neonatal Encephalopathy, Mutation
- 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
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- New York University, Universität Tübingen, Heinrich-Heine University, Duesseldorf
- Study start
- 18 May 2023 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 8 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HPDL deficiency | – | Other: Patient Registry, Other: Dry blood spots samplingPatients with HPDL mutations |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older 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.
Key inclusion criteria (6 listed)
- Any individuals diagnosed with HPDL variants
- Clinical diagnosis can include:
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Patient RegistryParticipants who have been diagnosed with HPDL mutations will be enrolled to patient registry. | Other | HPDL deficiency |
| Dry blood spots samplingDry blood splots require 500nl of blood. | Other | HPDL deficiency |
Primary outcome
Clinician questionnaire
Time frame: 12 months
Clinician-reported clinical and genetic confirmation of HPDL mutations
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Background: PubMed 33188300Ghosh 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.
- Background: PubMed 34471290Banh RS, Kim ES, Spillier Q, Biancur DE, Yamamoto K, Sohn ASW, Shi G, Jones DR, Kimmelman AC, Pacold ME. The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway. Nature. 2021 Sep;597(7876):420-425. doi: 10.1038/s41586-021-03865-w. Epub 2021 Sep 1.
- Derived from this study: PubMed 40368591Lee EH, Kim-Mcmanus O, Yang JH, Haas R, Zaki MS, Abdel-Salam GMH, Nakamura Y, Abdel-Hamind MS, Ebrahimi-Fakhari D, Alecu JE, Brunetti-Pierri N, Srinivasan VM, Gowda VK, Gross S, Alanay Y, Najarzadeh Totbati P, Yadavilli M, Friedman L, Ojeda NM, Gleeson JG. HPDL Variant Type Correlates With Clinical Disease Onset and Severity. Ann Clin Transl Neurol. 2025 Jul;12(7):1360-1367. doi: 10.1002/acn3.70047. Epub 2025 May 14.
- website for patient registrationLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Joseph Gleeson principal investigator
UCSD
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mitochondrial Encephalomyopathies and Hereditary Spastic Paraplegia, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Eun Hae Lee (8582460547, gleesonlab@health.ucsd.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinician questionnaire (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05848271, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2025.