Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)

Movement Disorders Clinical Trial

Official title:

Investigating the Genetic Basis of Hereditary Spastic Paraplegia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05354622
• Other study ID #: P00039630
• Status: Recruiting
• Start date: April 25, 2022
• Est. completion date: April 29, 2027

Study information

• Verified date: September 2023
• Source: Boston Children's Hospital
• Contact: Darius Ebrahimi-Fakhari, MD, PhD
• Phone: 617-355-8356
• Email: hsp.research[@]childrens.harvard.edu
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The purpose of the HSP Sequencing Initiative is to better understand the role of genetics in hereditary spastic paraplegia (HSP) and related disorders. The HSPs are a group of more than 80 inherited neurological diseases that share the common feature of progressive spasticity. Collectively, the HSPs present the most common cause of inherited spasticity and associated disability, with a combined prevalence of 2-5 cases per 100,000 individuals worldwide.

In childhood-onset forms, initial symptoms are often non-specific and many children may not receive a diagnosis until progressive features are recognized, often leading to a significant diagnostic delay. Genetic testing in children with spastic paraplegia is not yet standard practice. In this study, the investigators hope to identify genetic factors related to HSP. By identifying different genetic factors, the investigators hope that over time we can develop better treatments for sub-categories of HSP based on cause.

Description:

The hereditary spastic paraplegias (HSP) are a group of more than 80 inherited neurogenetic diseases that share the common feature of progressive spasticity. Collectively, the HSPs present the most common cause of inherited spasticity and associated disability, with a combined prevalence of 2-5 cases per 100,000 individuals worldwide. In childhood-onset forms, initial symptoms are often non-specific and many children may not receive a diagnosis until progressive features are recognized, often leading to a significant diagnostic delay. Genetic testing in children with spastic paraplegia is not yet standard practice.

The clinical diagnosis of HSP does not suggest anything about its molecular cause, with a wide range of outcomes dependent on the gene affected. The recent advances in HSP genetics speak to the importance of the field and the need for a more detailed study. Moreover, the relations between clinical features and genetic mechanisms are not well understood.

Given the influence of genetics on the likelihood of developing HSP as well as the complexity and diversity of the phenotypes, progress in HSP genetics will require efforts looking at relatively large samples of the HSP population. By bringing together very detailed phenotype information with high resolution DNA analyses, and using new approaches for comparing sequence information in candidate genes or looking for phenotype/genotype associations via genome-wide scanning, the investigators aim to be a leader in this emerging area of HSP research.

The aims of this study include:

1. To identify genetic findings (single nucleotide changes or copy number variants) in patients with progressive spastic paraplegia and related disorders.

2. To correlate molecular findings with HSP phenotypes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: April 29, 2027
• Est. primary completion date: April 29, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 30 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of progressive spasticity

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Hereditary Spastic Paraplegia
• Motor Neuron Disease
• Movement Disorders
• Muscle Spasticity
• Neurodegenerative Diseases
• Paraplegia
• Pediatric Disorder
• Spastic Paraplegia, Hereditary
• Spasticity, Muscle

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Boston Children's Hospital	Boston Children's Hospital - Children's Rare Disease Cohorts Initiative

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identify Genetic Findings	Identifying genetic variants in patients with progressive spastic paraplegia	An average of 1 year
Primary	Correlating Genetic Findings with HSP Phenotypes	Comparing phenotype/genotype associations via genome wide scanning	An average of 1 year