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

Sponsor

SwanBio Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05008874

Collaborator

(none)

Enrollment

Locations

46.3

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
AMN AMN Gene Mutation X-ALD	Other: Natural History Observation

Detailed 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).

Study Design

Study Type:

Observational

Anticipated Enrollment :

80 participants

Observational Model:

Cohort

Time Perspective:

Other

Official Title:

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

Actual Study Start Date :

Jun 21, 2021

Anticipated Primary Completion Date :

Apr 30, 2023

Anticipated Study Completion Date :

May 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Males with AMN Adult males with confirmed diagnosis of ALD and symptoms of AMN.	Other: Natural History Observation Data collection on progression of disease

Arm

Intervention/Treatment

Males with AMN

Adult males with confirmed diagnosis of ALD and symptoms of AMN.

Other: Natural History Observation

Data collection on progression of disease

Outcome Measures

Primary Outcome Measures

Disease progression [2 years]
Characterize disease progression in adults diagnosed with AMN in serial clinical evaluations of walking

Secondary Outcome Measures

Change in Quality of Life [2 years]
Characterize the Change in multiple Quality of Life (QoL) parameters over time

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Male adults aged ≥18 years
Diagnosed with ALD based on elevated VLCFA assay and pedigree analysis
Clinical evidence of spinal cord involvement with EDSS score between 1 and 6.5

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Neuroscience Health Center	Stanford	California	United States	94304
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
3	University of Utah	Salt Lake City	Utah	United States	84112
4	University of Leipzig Medical Center	Leipzig		Germany
5	Amsterdam UMC	Amsterdam		Netherlands