Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)

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: NCT05354622

Recruitment Status : Recruiting

First Posted : April 29, 2022

Last Update Posted : March 13, 2023

See Contacts and Locations

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

Boston Children's Hospital - Children's Rare Disease Cohorts Initiative

Information provided by (Responsible Party):

Darius Ebrahimi-Fakhari, Boston Children's Hospital

Study Description

Brief 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.

Condition or disease
Hereditary Spastic Paraplegia Neurodegenerative Diseases Pediatric Disorder Spasticity, Muscle Motor Neuron Disease Movement Disorders

Detailed 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:

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

Study Design

Layout table for study information

Study Type :	Observational [Patient Registry]
Estimated Enrollment :	200 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Target Follow-Up Duration:	5 Years
Official Title:	Investigating the Genetic Basis of Hereditary Spastic Paraplegia
Actual Study Start Date :	April 25, 2022
Estimated Primary Completion Date :	April 29, 2027
Estimated Study Completion Date :	April 29, 2027

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: Amyotrophic Lateral Sclerosis Paraplegia Hereditary Spastic Paraplegia Infantile-onset Ascending Hereditary Spastic Paralysis Spastic Paraplegia 11 Primary Lateral Sclerosis Charcot-Marie-Tooth Disease Hereditary Neuropathy With Liability to Pressure Palsies Roussy Levy Syndrome

U.S. FDA Resources

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

Identify Genetic Findings [ Time Frame: An average of 1 year ]
Identifying genetic variants in patients with progressive spastic paraplegia
Correlating Genetic Findings with HSP Phenotypes [ Time Frame: An average of 1 year ]
Comparing phenotype/genotype associations via genome wide scanning

Biospecimen Retention: Samples With DNA

Blood sample or Buccal Swab

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:	1 Month to 30 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Male or female, under 30 years, with suspected HSP

Criteria

Inclusion Criteria:

Clinical diagnosis of progressive spasticity

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): NCT05354622

Contacts

Layout table for location contacts

Contact: Darius Ebrahimi-Fakhari, MD, PhD	617-355-8356	Darius.Ebrahimi-Fakhari@childrens.harvard.edu
Contact: Amy Tam, BS	617-355-2698	amy.tam@childrens.harvard.edu

Locations

Layout table for location information

United States, Massachusetts
Boston Children's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Amy Tam 617-355-2698 amy.tam@childrens.harvard.edu

Sponsors and Collaborators

Boston Children's Hospital

Boston Children's Hospital - Children's Rare Disease Cohorts Initiative

Investigators

Layout table for investigator information

Principal Investigator:	Darius Ebrahimi-Fakhari, MD, PhD	Boston Children's Hospital

More Information

Layout table for additonal information

Responsible Party:	Darius Ebrahimi-Fakhari, Principal Investigator, Boston Children's Hospital
ClinicalTrials.gov Identifier:	NCT05354622
Other Study ID Numbers:	P00039630
First Posted:	April 29, 2022 Key Record Dates
Last Update Posted:	March 13, 2023
Last Verified:	March 2023

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 Darius Ebrahimi-Fakhari, Boston Children's Hospital:


Hereditary Spastic Paraplegia Spasticity Complex hereditary spastic paraplegia Early Onset hereditary spastic paraplegia Muscle Spasticity Neurodegenerative disease SPG3a SPG4 SPG11 SPG15 SPG26	SPG47 SPG50 SPG51 SPG52 Movement disorder Adaptor protein complex 4 Neurogenetic disorder Genetic Disease Neurodevelopmental disorders Musculoskeletal Disease

Additional relevant MeSH terms:

Layout table for MeSH terms

Muscle Spasticity Paraplegia Spastic Paraplegia, Hereditary Hereditary Sensory and Motor Neuropathy Movement Disorders Neurodegenerative Diseases Motor Neuron Disease Amyotrophic Lateral Sclerosis Disease Pathologic Processes Muscular Diseases Musculoskeletal Diseases Muscle Hypertonia Neuromuscular Manifestations Neurologic Manifestations	Nervous System Diseases Central Nervous System Diseases Paralysis Neuromuscular Diseases Spinal Cord Diseases TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases Nervous System Malformations Heredodegenerative Disorders, Nervous System Polyneuropathies Peripheral Nervous System Diseases Congenital Abnormalities Genetic Diseases, Inborn

To Top