Registry and Natural History Study for AP-4 Associated Hereditary Spastic Paraplegia (AP-4-HSP) (AP-4-HSP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT04712812

Recruitment Status : Recruiting

First Posted : January 15, 2021

Last Update Posted : January 15, 2021

See Contacts and Locations

Sponsor:

Collaborator:

CureAP4 Foundation

Information provided by (Responsible Party):

Mustafa Sahin, Boston Children's Hospital

Study Description

Brief Summary:

The Registry and Natural History Study for AP-4 Associated Hereditary Spastic Paraplegia (AP-4-HSP) is focused on gathering longitudinal clinical data as well as biological samples (skin and/or blood and/or saliva )from male or female patients of all ages with (1) a clinical diagnosis of hereditary spastic paraplegia and/or (2) the presence of variants in AP4-HSP related genes and/or be a relative of a person with such a diagnosis. Currently, the treatment for this disorder is generally symptomatic and available therapies improve quality of life, but are grossly inefficient in slowing the disease progression. Access to the registry information will be limited to the study staff who are responsible for recruitment and maintenance of the registry. The investigators hope that recruitment into registry for studies will advance knowledge of the causes, clinical course, diagnosis and treatment of these conditions.

Condition or disease
Hereditary Spastic Paraplegia SPG47 SPG50 SPG51 SPG52 AP4-related Hereditary Spastic Paraplegia

Detailed Description:

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 Design

Layout table for study information

Study Type :	Observational [Patient Registry]
Estimated Enrollment :	400 participants
Observational Model:	Cohort
Time Perspective:	Prospective
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

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Spastic paraplegia type 11 Spastic paraplegia type 8 Spastic paraplegia type 49 Spastic paraplegia type 31 Troyer syndrome Spastic paraplegia type 3A Infantile-onset ascending hereditary spastic paralysis Silver syndrome Spastic paraplegia type 15 Spastic paraplegia type 4 Fatty acid hydroxylase-associated neurodegeneration Spastic paraplegia type 7 Spastic paraplegia type 5A Spastic paraplegia type 2

Genetic and Rare Diseases Information Center resources: Paraplegia Hereditary Spastic Paraplegia Infantile-onset Ascending Hereditary Spastic Paralysis AP-4-Associated Hereditary Spastic Paraplegia Charcot-Marie-Tooth Disease Hereditary Neuropathy With Liability to Pressure Palsies Roussy Levy Syndrome

U.S. FDA Resources

Groups and Cohorts

Group/Cohort
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.

Outcome Measures

Primary Outcome Measures :

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.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

Male or female patients of all ageswith a known diagnosis of spastic hereditary paraplegia and/or an AP-4-HSP related gene mutation, and/or their family members of interest (if applicable).

Criteria

Inclusion Criteria:

A clinical diagnosis of hereditary spastic paraplegia
The presence of a variant in AP-4-HSP related genes and/or a relative of a person with such a diagnosis

Exclusion Criteria:

Not having such a diagnosis and/or not being related to such individual

Contacts and Locations

Information from the National Library of Medicine

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

Contacts

Layout table for location contacts

Contact: Darius Ebrahimi-Fakhari, MD, PhD	617-355-6388	Darius.Ebrahimi-Fakhari@childrens.harvard.edu
Contact: Gregory Geisel, BS	617-919-1476	AP4HSP.research@childrens.harvard.edu

Locations

Layout table for location information

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.research@childrens.harvard.edu
Principal Investigator: Mustafa Sahin, MD, PhD
Sub-Investigator: Darius Ebrahimi-Fakhari, MD, PhD

Sponsors and Collaborators

Boston Children's Hospital

CureAP4 Foundation

More Information

Layout table for additonal information

Responsible Party:	Mustafa Sahin, Professor of Neurology, Boston Children's Hospital
ClinicalTrials.gov Identifier:	NCT04712812
Other Study ID Numbers:	P00033016
First Posted:	January 15, 2021 Key Record Dates
Last Update Posted:	January 15, 2021
Last Verified:	January 2021

Layout table for additional information

Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Mustafa Sahin, Boston Children's Hospital:


AP4-HSP AP4 SPG AP-4	AP-4-HSP Spastic Paraplegia Adapter Protein 4

Additional relevant MeSH terms:

Layout table for MeSH terms

Muscle Spasticity Paraplegia Spastic Paraplegia, Hereditary Muscular Diseases Musculoskeletal Diseases Muscle Hypertonia Neuromuscular Manifestations Neurologic Manifestations Nervous System Diseases Paralysis	Hereditary Sensory and Motor Neuropathy Nervous System Malformations Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Polyneuropathies Peripheral Nervous System Diseases Neuromuscular Diseases Congenital Abnormalities Genetic Diseases, Inborn

To Top