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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: AMN; AMN Gene Mutation; X-ALD
• Intervention / Treatment: 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).

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.

• Study Type: Observational
• Enrollment (Actual): 65

Contacts and Locations

Study Locations

• Germany
  • Leipzig, Germany
    • University of Leipzig Medical Center
• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam UMC
• United States
  • California
    • Stanford, California, United States, 94304
      • Stanford Neuroscience Health Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10065
      • Weill Medical College of Cornell University
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult males diagnosed with ALD (without cerebral disease) and symptoms of AMN who have no other major confounding comorbidities.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease progression	Characterize disease progression in adults diagnosed with AMN in serial clinical evaluations of walking	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Quality of Life	Characterize the Change in multiple Quality of Life (QoL) parameters over time	5 years

Collaborators and Investigators

• Sponsor: SwanBio Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2021
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: August 12, 2021
• First Submitted That Met QC Criteria: August 12, 2021
• First Posted (Actual): August 17, 2021

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Natural History; Adrenoleukodystrophy; X-linked Adrenoleukodystrophy; Metabolic Diseases; Metabolism, Inborn Errors; ALD; HSP; Heredodegenerative Disorders, Nervous System; Leukoencephalopathies; Adrenomyeloneuropathy; Brain Diseases, Metabolic, Inborn; Demyelinating Diseases; Peroxisomal Disorders; Adrenal Insufficiency; Hereditary Spastic Paraplegia; Brain Diseases, Metabolic; AMN; X-ALD; Myeloneuropathy; Spastic paraplegia; ABCD1; ALDP; CALD; CCALD; Hereditary Central Nervous System Demyelinating Diseases
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Disease Attributes; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Paralysis; Muscle Hypertonia; Disease Progression; Muscle Spasticity; Paraplegia
• Other Study ID Numbers: SBTNHX-CT901

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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