Evaluation of Outcome Metrics in Alexander Disease (AxD Outcomes)

The purpose of this study is to define the natural history of Alexander Disease, a leukodystrophy that causes neurological dysfunction. Investigators will obtain clinical outcome assessments to measure how the disease affects a patient's gross motor, fine motor, speech and language function, swallowing, and quality of life. Specimens are collected to measure glial fibrillary acidic protein (GFAP) levels in cerebrospinal fluid (CSF) and blood. The data obtained from this study will be used for the design of future treatment trials.

Study Overview

• Status: Recruiting
• Conditions: Alexander Disease

Detailed Description

Participants will be asked to complete physical examinations including physical therapy, occupational therapy, speech and language therapy, neurocognitive and swallowing assessments. Patients (or caretakers) may be asked to complete questionnaires as well. Specimen collection is an optional procedure. The study asks for participants to return at least once yearly to repeat assessments.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Amy Waldman, MD; Phone Number: 215-590-1719
• Study Contact Backup: Name: Geraldine Liu, MA; Phone Number: 267-425-2063; Email: liug@chop.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Contact: Geraldine Liu, MA; Phone Number: 267-425-2063; Email: liug@chop.edu
      • Principal Investigator: Amy T Waldman, MD, MSCE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients who have been diagnosed with Alexander Disease.

Description

Inclusion Criteria:

• Diagnosed with Alexander Disease

Exclusion Criteria:

• Other Leukodystrophies will not be enrolled

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Gross Motor Function Over Time	Total score and dimensional scores (rolling/supine, crawling/traveling, sitting, standing, and walking/running) will be calculated at each visit. Change in total and dimensional scores over time will be assessed.	Up to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Bruininks-Oseretsky Test of Motor Proficiency Over Time	Composite score and scores for the 4 sub-scales will be calculated at each visit. Change in composite and subscale scores over time will be assessed.	Up to 10 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Peabody Developmental Motor Scales Over Time	Composite score and 4 sub-scales (reflexes, stationary, locomotion, object manipulation) will be calculated at each visit. Change in composite and subscale scores over time will be assessed.	Up to 10 years
Change in Rosetti Infant-Toddler Language Scale Over Time	Change in six sub-scales (Interaction-Attachment, Pragmatics, Gesture, Play, Language Comprehension, and Language Expression) will be assessed at each visit for age applicable patients.	Up to 10 years
Change in Swallowing Performance Over Time	A clinical swallow evaluation will be performed and assessed for change annually using an ordinal classification scale based on performance.	Up to 10 years
Change in Clinical Evaluation of Language Fundamentals Over Time	Changes in the comprehensive scores will be assessed at baseline and then annually at each visit which will be scheduled within ± 2 months around the specified time point, for up to 10 years	Up to 10 years
Change in Peabody Picture Vocabulary Test Over Time	Changes in comprehensive scores will be assessed at baseline and then annually at each visit which will be scheduled within ± 2 months around the specified time point, for up to 10 years	Up to 10 years
Change in Goldman-Fristoe Test of Articulation Over Time	Changes in standardized scores will be assessed at baseline and then annually at each visit which will be scheduled within ± 2 months around the specified time point, for up to 10 years	Up to 10 years
Change in Physical Health Quality of Life for Patients	Surveys will be used as a composite measure to understand a patient's physical health and how it may change during their disease course. An aggregate measure of survey scores will be analyzed at baseline and end of study. Compass-31, PedsQL-Gastrointestinal Symptom Scales, Patient Global Impression of Change, Patient Global Impression of Severity, Alexander Disease Patient Domain Impression of Change, Alexander Disease Patient Domain Impression of Severity, Most Bothersome Symptom, PROMIS Pediatric Physical Function-Mobility-Short Form, PROMIS Pediatric Physical Function-Pain Interference-Short Form, PROMIS Pediatric Physical Function-Upper Extremity- Short Form, Pediatric Bowel Movement Scoring Tool-Child Supplement II (PBMST), Caregiver Priorities and Child Health Index of Life with Disabilities (CP Child), Emesis Frequency Ladder, Multiple Sclerosis Quality of Life (MSQoL-54)	Up to 10 years
Change in Physical Health Quality of Life for Parents/Caregivers	Surveys will be used as a composite measure to understand a parents/caregiver physical health and how it may change during their child/spouse disease course. An aggregate measure of survey scores will be analyzed at baseline and end of study. Multiple Sclerosis Quality of Life (MSQoL-54)	Up to 10 years
Change in Mental Health Quality of Life for Patients	Surveys will be used as a composite measure to understand a patient's mental health and how it may change during their disease course. An aggregate measure of survey scores will be analyzed at baseline and end of study. PedsQL Quality of Life Inventory, Multiple Sclerosis Quality of Life (MSQoL-54)	Up to 10 years
Change in Mental Health Quality of Life for Parents/Caregivers	Surveys will be used as a composite measure to understand a parents/caregiver mental health and how it may change during their child/spouse disease course. An aggregate measure of survey scores will be analyzed at baseline and end of study. Multiple Sclerosis Quality of Life-54 (MSQoL-54), Hospital Anxiety and Depression Scale (HADS), and Euro-QoL 5 Dimensions (EQ5D-5L)	Up to 10 years

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: University of Wisconsin, Madison; Ionis Pharmaceuticals, Inc.; Pennsylvania Department of Health
• Investigators: Principal Investigator: Amy Waldman, MD, Children's Hospital of Philadelphia

Publications and helpful links

General Publications

• Joung J, Gallison K, Sollee JJ, Vigilante N, Cooper H, Liu GW, Ballester L, Faig W, Waldman AT. Acquisition and Loss of Developmental Milestones and Time to Disease-Related Outcomes in Cerebral Alexander Disease. J Child Neurol. 2023 Dec;38(13-14):672-678. doi: 10.1177/08830738231210040. Epub 2023 Nov 3.

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2016
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: February 19, 2016
• First Submitted That Met QC Criteria: March 16, 2016
• First Posted (Estimated): March 21, 2016

Study Record Updates

• Last Update Posted (Actual): January 15, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Alexander Disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Demyelinating Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Alexander Disease
• Other Study ID Numbers: 16-012649

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data and Samples will be shared with University of Wisconsin, Madison.
• IPD Sharing Time Frame: Up to 10 years
• IPD Sharing Access Criteria: Dr. Albee Messing and Tracy Hagemann, PHD are listed in the HIPAA section of the approved informed consent.
• IPD Sharing Supporting Information Type: ICF

Drug and device information, study documents

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