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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
Sponsor:
Collaborator:
CureAP4 Foundation
Information provided by (Responsible Party):
Mustafa Sahin, Boston Children's Hospital

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:

  1. Create a registry to perform an initial cross sectional analysis of clinical, imaging and molecular data to establish the disease spectrum.
  2. Create a repository of biological samples and collection of longitudinal clinical data that helps establish the natural history of AP-4-HSP.
  3. Create a registry that allows for re- identification and re-contact of participants by appropriate investigators.

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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


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.



Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



Information from the National Library of Medicine

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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

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
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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
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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
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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

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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:
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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