Study of Disease Progression in Adults With Inherited Forms of Spastic Paraplegia

AMN Clinical Trial

— CYGNET  

Official title:

Prospective, Retrospective, Multicenter, Observational Study of Disease Progression in Adults With Inherited Forms of Spastic Paraplegia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05008874
• Other study ID #: SBTNHX-CT901
• Status: Active, not recruiting
• Start date: June 21, 2021
• Est. completion date: June 1, 2028

Study information

• Verified date: September 2023
• Source: SwanBio Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The course of AMN-related disabilities over time is poorly or incompletely understood due to a limited number of patients and lack of treatments. This study will help obtain a better understanding of the progression of disease with AMN and facilitate efficient clinical development of future interventional medications.

Description:

Progressive weakness and spasticity of the legs are characteristics of numerous disorders and conditions, including those that are inherited neurological disorders. Adrenomyeloneuropathy (AMN) is an example of an inherited form of spastic paraplegia. Adrenoleukodystrophy (ALD) is a progressive neurodegenerative disorder caused by a mutation in the ABCD1 gene localized to the X-chromosome (Xq28). The ABCD1 gene encodes a peroxisomal adenosine triphosphate (ATP) binding cassette transporter responsible for transport of very long chain fatty acids (VLCFA) from the cytosol into the peroxisome for degradation. A mutation in ABCD1 results in reduction in the degradation of the VLCFA by peroxisomal β-oxidation, and saturated VLCFA, in particular C26:0, accumulate in tissues and body fluids (i.e., brain, nervous system, adrenal glands). One of the key clinical symptoms during aging of ALD patients is a slowly progressive axonopathy affecting sensory ascending and motor descending spinal cord tracts with 100% penetrance in men, an ALD phenotype known as AMN. There are no treatment options available, which leaves AMN patients with a progressive disorder that leads to lifelong physical disability. The progressive dying-back axonopathy represents the core clinical feature of AMN, with onset usually between 20 and 30 years of age in male participants. The initial symptoms include progressive stiffness and weakness of the legs, impaired vibration and position senses in the lower limbs, falls, sphincter disturbances and impotence, as well as scarce scalp hair (alopecia). About 66% of male AMN patients have adrenocortical insufficiency (Addison disease). The course of AMN-related disabilities over time is poorly or incompletely understood due to a limited number of patients and lack of treatments. This study will help obtain a better understanding of the progression of disease with AMN and facilitate efficient clinical development of future SwanBio interventional medications.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 65
• Est. completion date: June 1, 2028
• Est. primary completion date: December 30, 2027
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male adults aged =18 years

2. Diagnosed with ALD based on elevated VLCFA assay and pedigree analysis

3. Clinical evidence of spinal cord involvement with EDSS score between 1 and 6.5

Exclusion Criteria:

1. Diagnosed with cerebral inflammatory disease or has a history of diagnosis with cerebral inflammatory disease

2. Unstable, clinically significant neurologic (other than the disease being studied), psychiatric, cardiovascular, ophthalmologic, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, hematopoietic, or endocrine disease (other than adrenal insufficiency) or other abnormality, which may impact the ability to participate in the study or that may potentially confound the study results

3. Participant who, in the opinion of the Investigator, has any other medical or psychological condition or social circumstances which would impair their ability to participate reliably in the assessments, or who may increase the risk to themselves or others by participating

Related Conditions & MeSH terms

• AMN
• Disease Progression
• Muscle Spasticity
• Paraplegia
• X-ALD

Intervention

Other:
• Natural History Observation
Data collection on progression of disease

Locations

Country	Name	City	State
Germany	University of Leipzig Medical Center	Leipzig
Netherlands	Amsterdam UMC	Amsterdam
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Weill Medical College of Cornell University	New York	New York
United States	University of Utah	Salt Lake City	Utah
United States	Stanford Neuroscience Health Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
SwanBio Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease progression	Characterize disease progression in adults diagnosed with AMN in serial clinical evaluations of walking	5 years
Secondary	Change in Quality of Life	Characterize the Change in multiple Quality of Life (QoL) parameters over time	5 years