Giant Axonal Neuropathy Natural History Study

Clinical Study of Giant Axonal Neuropathy

Giant Axonal Neuropathy (GAN) is a devastating and rare childhood disease. Children with GAN develop increasing muscle weakness, impaired sensation, and at times mental retardation. GAN starts in infancy, leads to significant disability, and typically leads to death within the first 30 years of life. GAN is caused by a defect in the "gigaxonin" (GAN) gene, resulting in pathologically enlarged and dysfunctional nerves. Currently, there is no effective therapy. To find out what medications can help patients with GAN, the investigators have to conduct clinical trials. In this study, the investigators propose to prepare for future clinical trials and will invite GAN patients to join our research effort.

The investigators will examine them regularly to better understand their disease. The visits will include questions, a physical exam, blood drawing, a lumbar puncture, and a skin biopsy. The visits will also include tests that assess the electrical conductivity of the patients' nerves as well as a test to measure the patients' brain wave activity. In addition, the investigators will be performing tests to evaluate the patients' motor function, their vision, and thinking ability. Identifying an effective GAN treatment is very important because there is currently none. Clinical trials are the only way to decide whether a new treatment works in GAN patients or not.

With the future objective of conducting clinical trials in GAN, the proposed project has three specific aims. The first is to plan for clinical trials by developing reliable outcome measures, and establishing the infrastructure needed to carry out efficient clinical trials. The second is to further characterize the patient population from a clinical and molecular point of view, and the third aim is to utilize the information gathered in this study to further pre-clinical GAN drug development to select candidate drugs.

Study Overview

• Status: Terminated
• Conditions: Giant Axonal Neuropathy

Detailed Description

Giant Axonal Neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder that appears during childhood and affects both the central and peripheral nervous systems. This disorder is generally characterized by motor and sensory involvement including progressive and predominant distal clumsiness, muscle weakness, and pronounced gait disturbances. GAN is caused by various mutations in the GAN gene that encodes the protein gigaxonin. This leads to giant axonal swelling and degeneration due to substantial accumulation of neurofilaments in the axon. Currently, there is no effective therapy, with onset occurring before the age of seven, and death usually occurring between the first and third decade of life.

• Study Type: Observational
• Enrollment (Actual): 13

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Pediatric Neuromuscular Center

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

People diagnosed with Giant Axonal Neuropathy

Description

Inclusion Criteria:

1. Clinical diagnosis of Giant Axonal Neuropathy.
2. Documentation of the presence of a mutation in the GAN gene as determined by gene sequencing from a CAP/CLIA certified laboratory or an equivalent organization.
3. Parents or if applicable subjects must give informed consent must be capable of complying with the study procedures.
4. Willing and able to comply with all protocol requirements and procedures.

Exclusion Criteria:

1. Unwilling or unable to travel to Columbia University Medical Center.
2. Unstable medical condition precluding participation.
3. Significant respiratory compromise that would interfere with safe travel to site of evaluation.
4. Having a contraindication to the MRI safety requirements, including pacemaker or other implanted electrical device, brain stimulator, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), implanted delivery pump, shrapnel fragments, or history of claustrophobia.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Gross Motor Function Measure (GMFM)	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Nerve Conduction Study (NCS)/Motor Unit Number Estimation (MUNE)	Up to 24 months
Somatosensory Evoked Potential (SSEP)	Up to 24 months
Brainstem Auditory Evoked Response (BAER)	Up to 24 months
Pulmonary Function Testing (PFT)/Forced Vital Capacity (FVC)	Up to 24 months

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: University of North Carolina, Chapel Hill

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: December 29, 2011
• First Submitted That Met QC Criteria: December 30, 2011
• First Posted (Estimate): January 2, 2012

Study Record Updates

• Last Update Posted (Estimate): January 27, 2017
• Last Update Submitted That Met QC Criteria: January 26, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Observational Study; Natural History Study; Neuromuscular Disease; GAN; Giant Axonal Neuropathy
• Additional Relevant MeSH Terms: Nervous System Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Hereditary Sensory and Motor Neuropathy; Peripheral Nervous System Diseases; Giant Axonal Neuropathy
• Other Study ID Numbers: AAAI4500

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