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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hereditary Spastic Paraplegia; SPG50; SPG47; SPG51; SPG52; AP4-related Hereditary Spastic Paraplegia; Early Onset Hereditary Spastic Paraplegia; SPG4; SPG3A; SPG15; SPG11

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
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Amy Tam, BS; Phone Number: 617-355-2698; Email: hsp.research@childrens.harvard.edu
• Study Contact Backup: Name: Darius Ebrahimi-Fakhari, MD, PhD; Phone Number: 617-355-6388; Email: hsp.research@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Darius Ebrahimi-Fakhari, MD, PhD; Phone Number: 617-355-6388; Email: Darius.Ebrahimi-Fakhari@childrens.harvard.edu
      • Principal Investigator: Darius Ebrahimi-Fakhari, MD, PhD
      • Contact: Amy Tam, BS; Phone Number: 16173552698; Email: amy.tam@childrens.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• 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).

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establishment of data repository	Create a registry to perform an initial cross sectional analysis of clinical, imaging and molecular data to establish the disease spectrum.	Through study completion, an average of 1 year
Establishment of bio-repository	Create a repository of biological samples and collection of longitudinal clinical data that helps establish the natural history of early onset HSP.	Through study completion, an average of 1 year
Registry for recontact	Create a registry that allows for re-identification and re-contact of participants by appropriate investigators.	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: CureAP4 Foundation

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2020
• Primary Completion (Estimated): April 26, 2024
• Study Completion (Estimated): April 26, 2025

Study Registration Dates

• First Submitted: January 12, 2021
• First Submitted That Met QC Criteria: January 14, 2021
• First Posted (Actual): January 15, 2021

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: HSP; Early onset; AP4-HSP; AP4; SPG; AP-4; AP-4-HSP; Spastic Paraplegia; Adapter Protein 4; Early onset HSP
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Manifestations; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Paralysis; Muscle Hypertonia; Polyneuropathies; Hereditary Sensory and Motor Neuropathy; Muscle Spasticity; Paraplegia; Spastic Paraplegia, Hereditary
• Other Study ID Numbers: P00033016

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No