Natural History of the Leukodystrophies

• ClinicalTrials.gov Identifier: NCT02843555
• Recruitment Status: Completed
• First Posted: July 26, 2016
• Last Update Posted: March 22, 2019
• Sponsor: Baylor Research Institute
• Information provided by (Responsible Party): Baylor Research Institute

Tracking Information

• First Submitted Date: April 7, 2016
• First Posted Date: July 26, 2016
• Last Update Posted Date: March 22, 2019
• Actual Study Start Date: January 23, 2019
• Actual Primary Completion Date: January 23, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 21, 2016)

Neuropsychological evaluation to measure baseline cognitive function and detect signs of dementia over time [ Time Frame: Every 52 weeks up to 5 years ]

Neuropsychological status is evaluated at Baseline and no less than once every year for the duration of the study to assess for any deterioration in function

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 21, 2016)

• Evoked potentials to assess involvement of different areas of brain over time [ Time Frame: Every 52 weeks up to 5 years ]
  Evoked potentials are evaluated at Baseline and no less than once every year for the duration of the study to assess for changes in function
• MRI of the brain to assess involvement of different areas of the brain over time [ Time Frame: Every 52 weeks ]
  Changes in the brain are assessed at Baseline and no less than once every year for the duration of the study to assess for changes
• Electroencephalogram to assess involvement of different areas of the brain over time [ Time Frame: Every 52 weeks up to 5 years ]
  EEG is assessed at Baseline and no less than once a year for the duration of the study to assess for changes in function
• Electromyelogram to assess for changes in muscle function over time [ Time Frame: Every 52 weeks up to 5 years ]
  EMG is assessed at Baseline and no less than once a year for the duration of the study to assess for changes in function
• Nerve Conduction study to assess abnormalities in affected nerves [ Time Frame: Every 52 weeks up to 5 years ]
  Nerve conduction is assessed at Baseline and no less than once a year for the duration of the study to assess for changes in function
• Skin biopsy for to look for evidence of storage disease [ Time Frame: Baseline ]
• DNA Studies to search for mutations in genes of structural myelin proteins or genes that control myelin production [ Time Frame: Baseline ]
• Spinal Tap to look for diagnostic markers of leukodystrophy [ Time Frame: Baseline ]
• Nerve Biopsy to look for pathological abnormalities in affected nerves [ Time Frame: Baseline ]
• Neuro-ophthalmological exam to assess for abnormalities in the eye [ Time Frame: Every 52 weeks up to 5 years ]
  Eyes are assessed at Baseline and no less than once a year for the duration of the study to assess for changes in function

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Natural History of the Leukodystrophies
• Official Title: The Etiology, Pathogenesis, and Natural History of the Leukodystrophies

Brief Summary

The purpose of this study is to:

1. define novel homogeneous groups of patients with LDs and
2. work toward finding the cause of these disorders.

• Detailed Description: Patients with leukodystrophies (LDs) of unknown etiology are a heterogeneous group but constitute the second largest group of genetic white matter diseases. In order to find the cause of leukodystrophies, patients with LDs of unknown cause will be analyzed clinically, neurophysiologically, biochemically and genetically. Patients would have been diagnosed as having no known leukodystrophies at outside centers. At the Baylor University Medical Center, such patients will undergo a series of neuropsychological, blood, urine, spinal fluid, radiological, and peripheral tissue pathological tests. Some of these tests will be part of a standard battery while others will be tailored to individual patients. Patients will be followed yearly or as necessary. Patients will be screened for mutations in genes coding for structural myelin proteins. In some patients in whom all tests yielded no information regarding the etiology of their disease, and in whom there is evidence to suggest involvement of the peripheral nervous system, a sural nerve biopsy will be considered. Sural nerve biopsy tissue will be evaluated using a novel combination of approaches including detailed pathological, immunohistochemical, and biochemical analysis of myelin proteins and lipids. Schwann cell biology and expression of myelin genes in the brain will also be investigated in situ. It is hoped that the present study will help clarify the nosology of the leukodystrophies and significantly advance our understanding of the pathogenesis of these diseases.
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Blood, urine, skin

• Sampling Method: Non-Probability Sample
• Study Population: Subjects identified with a leukodystrophy of unknown etiology
• Condition: Leukodystrophies
• Intervention: Not Provided

Study Groups/Cohorts

Leukodystrophy of unknown etiology

Subjects who may have an undiagnosed form of leukodystrophy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 21, 2019): 10
• Original Estimated Enrollment (submitted: July 21, 2016): 50
• Actual Study Completion Date: January 23, 2019
• Actual Primary Completion Date: January 23, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Subjects must:

• have clinical and radiographic signs of leukodystrophy without a specific etiology
• no diagnosis of adrenoleukodystrophy, adrenomyeloneuropathy, metachromatic leukodystrophy, Krabbe disease, Canavan disease, a well-defined amino acid organic acid disorder, or a systemic mitochondrial cytopathy.
• First-degree relatives of patients with leukodystrophies of unknown etiology (father, mother, siblings, or sons and daughters of the patients)
• Be able to travel to Baylor University Medical Center in Dallas Texas for evaluation and spend 5-8 working days on site
• Be able to tolerate a general exam and neurological exam
• Be able to tolerate a modest amount of blood drawing, provide a urine specimen, and have a skin biopsy(if not previously done)
• Be able to tolerate the performance of necessary neuroimaging studies to include EEG and Head MRI
• Be able to tolerate a neuropsychological testing and rehabilitation evaluation
• Be able to tolerate spinal tap or nerve biopsy if needed

Exclusion Criteria:

• Unable to travel to Baylor University Medical Center in Dallas Texas for evaluation
• Refusal to sign a study consent form
• Unable to tolerate the performance of the required testing

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02843555
• Other Study ID Numbers: 008-169
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Baylor Research Institute
• Study Sponsor: Baylor Research Institute
• Collaborators: Not Provided

Investigators

• Principal Investigator: Raphael Schiffmann, MD, MHS; Baylor University Medical Center, Baylor Institute of Metabolic Disease

• PRS Account: Baylor Research Institute
• Verification Date: March 2019