Clinical trial NCT05020743: Natural History Study in Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia
Official title: A Natural History Study of Patients With Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia (ALSP)
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: ALSP
Keywords: ALSP
CSF1R
leukoencephalopathy
Hereditary Diffuse Leukoencephalopathy with Spheroids
HDLS
CSF1R-related Leukoencephalopathy
Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia
CSF1R gene mutation
POLD
Pigmentary Orthochromatic Leukodystrophy
Lead sponsor: Vigil Neuroscience, Inc.
Sponsor class: INDUSTRY
First posted: 2021-08-25
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Definitive ALSP and Prodromal ALSP.

Brief summary: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare, rapidly progressing, genetic, neurodegenerative disease for which no definitive treatment options and limited information on the natural history of the disease are available. The structural, genetic, and neuropathophysiological abnormalities of ALSP lead to the onset of neurologic symptoms, such as moderate to severe motor and neuropsychiatric impairments. This natural history study will collect data to contribute to the development of future novel therapies that focus on the neuropathophysiological features that underlie ALSP and that are essential to reverse, delay, or stop progression of this debilitating disorder.


Eligibility criteria: Key Inclusion Criteria for Definitive ALSP patients:

1. Subjects who have documentation of a gene mutation in the CSF1R gene (prior to enrollment)
2. Subjects who fulfill both of the following criteria (a and b):

   a. More than two findings of clinical signs or symptoms in the following categories: i. Cognitive impairment or psychiatric problem ii. Pyramidal signs on neurological examination iii. Extrapyramidal signs, such as rigidity, tremor, abnormal gait, or bradykinesia iv. Epilepsy

   b. MRI findings consistent with ALSP: specifically, bilateral cerebral white matter lesions with or without thinning of the corpus callosum NOTE: Subjects with other causes of leukoencephalopathy, including vascular dementia, multiple sclerosis, or leukodystrophy (e.g., adrenoleukodystrophy, Krabbe disease, metachromatic leukodystrophy), will be excluded.
3. Subjects who, in the investigator's opinion, have demonstrated clinical progression of their ALSP within the past year.
4. Subjects who meet the criteria for definitive ALSP must have a designated study partner (i.e caregiver) who spends at least 4 hours per week with them. The study partner must be able and willing to assist the subject in complying with the study requirements, be able to provide information during study visits, and be willing to sign a study partner ICF. Subjects who do not have a study partner may be enrolled at the investigator's discretion if they are able to comply with protocol requirements.

Key Exclusion Criteria for Definitive ALSP patients:

1. Subjects with any neurological or psychiatric diseases that can produce cognitive, motor, or behavioral impairment similar to ALSP, including, but not limited to, Alzheimer's disease, frontotemporal dementia, ALS, stroke, Huntington disease, multiple sclerosis, Parkinson's disease, and Down syndrome, or with active alcohol/drug abuse
2. Subjects who are unable to undergo MRI
3. Subjects with any condition or situation that, in the opinion of the investigator or sponsor medical personnel, may place the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study.
4. Subjects who have previously undergone HSCT or plan to undergo HSCT within 12 months of the Screening/Baseline visit.

Primary outcomes:
measure: Magnetic Resonance Imaging (MRI)
timeFrame: Months 6, 12, 18, 24, 30, and 36 Months
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Investigative Site 4
state: California
city: Englewood
country: United States
facility: Investigative Site 5
state: Colorado
city: Boca Raton
country: United States
facility: Investigative Site 1
state: Florida
city: Jacksonville
country: United States
facility: Investigative Site 2
state: Florida
city: Boston
country: United States
facility: Investigative Site 11
state: Massachusetts
city: Philadelphia
country: United States
facility: Investigative Site 10
state: Pennsylvania
city: São Paulo
country: Brazil
facility: Investigative Site 12
city: London
country: Canada
facility: Investigative Site 3
state: Ontario
city: Leipzig
country: Germany
facility: Investigative Site 8
city: Tübingen
country: Germany
facility: Investigative Site 9
city: Amsterdam
country: Netherlands
facility: Investigative Site 6
city: London
country: United Kingdom
facility: Investigative Site 7
Study officials:
References: