Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia (HSP)

• ClinicalTrials.gov Identifier: NCT04712812
• Recruitment Status: Recruiting
• First Posted: January 15, 2021
• Last Update Posted: September 7, 2023
• Sponsor: Boston Children's Hospital
• Collaborator: CureAP4 Foundation
• Information provided by (Responsible Party): Darius Ebrahimi-Fakhari, Boston Children's Hospital

Tracking Information

• First Submitted Date: January 12, 2021
• First Posted Date: January 15, 2021
• Last Update Posted Date: September 7, 2023
• Actual Study Start Date: April 27, 2020
• Estimated Primary Completion Date: April 26, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 10, 2021)

• 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 early onset 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.

Original Primary Outcome Measures (submitted: January 14, 2021)

• 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.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
• Official Title: Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia (HSP)
• Brief Summary: The Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia (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 who exhibited onset of HSP symptoms at 18 years old or younger with (1) a clinical diagnosis of hereditary spastic paraplegia and/or (2) the presence of variants in 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. We hope that recruitment into registry for studies will advance knowledge of the causes, clinical course, diagnosis and treatment of these conditions.

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.

We aim to delineate the core clinical, imaging, and molecular features of pediatric onset hereditary spastic paraplegia. 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 a secure 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 early-onset forms of HSP and (2) To facilitate an 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 early onset HSP.
3. Create a registry that allows for re- identification and re-contact of participants by appropriate investigators.

• Study Type: Observational [Patient Registry]
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: 4 Years
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Male or female patients of all ages with onset of hereditary spastic paraplegia symptoms before the age of 18 years and/or an HSP related gene mutation, and/or their family members of interest (if applicable).

Condition

• Hereditary Spastic Paraplegia
• SPG47
• SPG50
• SPG51
• SPG52
• AP4-related Hereditary Spastic Paraplegia
• Early Onset Hereditary Spastic Paraplegia
• SPG4
• SPG3A
• SPG15
• SPG11

• Intervention: Not Provided

Study Groups/Cohorts

Proband with AP-4 Associated HSP

Male or female patients of all ages with (1) onset of hereditary spastic paraplegia symptoms before the age of 18 years and/or (2) the presence of variants in HSP related genes and/or a relative of a person with such a diagnosis.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 14, 2021): 400
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 26, 2025
• Estimated Primary Completion Date: April 26, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Onset of hereditary spastic paraplegia symptoms before the age of 18 years
• The presence of variants in 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Days and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Darius Ebrahimi-Fakhari, MD, PhD; 617-355-6388; hsp.research@childrens.harvard.edu

Contact: Amy Tam, BS; 617-355-2698; hsp.research@childrens.harvard.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04712812
• Other Study ID Numbers: P00033016
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Darius Ebrahimi-Fakhari, Boston Children's Hospital
• Original Responsible Party: Mustafa Sahin, Boston Children's Hospital, Professor of Neurology
• Current Study Sponsor: Boston Children's Hospital
• Original Study Sponsor: Same as current
• Collaborators: CureAP4 Foundation
• Investigators: Not Provided
• PRS Account: Boston Children's Hospital
• Verification Date: September 2023