Registry and Natural History Study for AP-4 Associated Hereditary Spastic Paraplegia (AP-4-HSP) (AP-4-HSP)
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|ClinicalTrials.gov Identifier: NCT04712812|
Recruitment Status : Recruiting
First Posted : January 15, 2021
Last Update Posted : January 15, 2021
|Condition or disease|
|Hereditary Spastic Paraplegia SPG47 SPG50 SPG51 SPG52 AP4-related Hereditary Spastic Paraplegia|
The hereditary spastic paraplegias (HSP) are a group of more than 80 neurodegenerative diseases that lead to progressive neurological decline. Collectively, the HSPs present the most common cause of inherited spasticity and associated disability. Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of complex HSP in children, called AP-4-associated HSP (or AP-4-HSP). This includes four different conditions: SPG47, SPG50, SPG51, and SPG52. The molecular mechanism in all four conditions is a loss-of-function of the AP-4; hence they are thought to share a similar clinical phenotype.
Published reports consist of small case series only and there has been no effort to systemically delineate the spectrum of the disease or its progression. The investigators aim to delineate the core clinical, imaging, and molecular features of AP-4-HSP across the age spectrum. This registry and natural history study will facilitate an early diagnosis, enables counseling and anticipatory guidance of affected families and will help define clinically meaningful endpoints for future interventional trials. Samples will be collected for the purpose of molecular and cellular investigation that will help identify biomarkers and novel targets for therapy. The samples and clinical information will be housed in the Translational Neuroscience Center and an AP-4-HSP REDcap database, respectively; both located in Boston Children's Hospital (BCH), but will be available to investigators around the world after approval.
The objectives of this protocol are to (1) To systematically document the clinical presentation and natural history of AP-4-associated HSP and (2) To facilitate early diagnosis, enable counseling and anticipatory guidance of affected families and help define clinically meaningful endpoints for future interventional traits.
Specifically, the aims are to:
- Create a registry to perform an initial cross sectional analysis of clinical, imaging and molecular data to establish the disease spectrum.
- Create a repository of biological samples and collection of longitudinal clinical data that helps establish the natural history of AP-4-HSP.
- Create a registry that allows for re- identification and re-contact of participants by appropriate investigators.
|Study Type :||Observational [Patient Registry]|
|Estimated Enrollment :||400 participants|
|Target Follow-Up Duration:||4 Years|
|Official Title:||Registry and Natural History Study for AP-4 Associated Hereditary Spastic Paraplegia (AP-4-HSP)|
|Actual Study Start Date :||April 27, 2020|
|Estimated Primary Completion Date :||April 26, 2024|
|Estimated Study Completion Date :||April 26, 2025|
Proband with AP-4 Associated HSP
Male or female patients of all ages with (1) a clinical diagnosis of hereditary spastic paraplegia and/or (2) the presence of variants in AP-4-HSP related genes and/or a relative of a person with such a diagnosis.
- Establishment of data repository [ Time Frame: Through study completion, an average of 1 year ]Create a registry to perform an initial cross sectional analysis of clinical, imaging and molecular data to establish the disease spectrum.
- Establishment of bio-repository [ Time Frame: Through study completion, an average of 1 year ]Create a repository of biological samples and collection of longitudinal clinical data that helps establish the natural history of AP-4-HSP.
- Registry for recontact [ Time Frame: Through study completion, an average of 1 year ]Create a registry that allows for re-identification and re-contact of participants by appropriate investigators.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04712812
|Contact: Darius Ebrahimi-Fakhari, MD, PhD||617-355-6388||Darius.Ebrahimi-Fakhari@childrens.harvard.edu|
|Contact: Gregory Geisel, BS||617-919-1476||AP4HSP.email@example.com|
|United States, Massachusetts|
|Boston Children's Hospital||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Darius Ebrahimi-Fakhari, MD, PhD 617-355-6388 Darius.Ebrahimi-Fakhari@childrens.harvard.edu|
|Contact: Gregory Geisel, BS 617-919-1476 AP4.firstname.lastname@example.org|
|Principal Investigator: Mustafa Sahin, MD, PhD|
|Sub-Investigator: Darius Ebrahimi-Fakhari, MD, PhD|