Desipramine in Infantile Neuroaxonal Dystrophy (INAD).

Study Overview
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Brief Summary
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This is a research study to find out if clinically prescribed desipramine is effective at improving the symptoms and slowing the progression of Infantile Neuroaxonal Dystrophy (INAD) in affected children. Participants will receive an initial oral dose of study drug once a day. This dose may be changed depending on response to study drug Clinically collected data will be recorded for up to 5 years. Investigators will also ask for participant permission to obtain a sample of child's skin biopsy from unused clinical sample previously collected for standard of care.

Detailed Description
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To be eligible participants must be able to swallow tablets The study drug is to be taken once daily Schedule of events. Day 0 - ECG and blood tests (4 ml or ¾ teaspoon) Day 3 - ECG and blood tests (4 ml or ¾ teaspoon) Day 7 - ECG and blood tests (4 ml or ¾ teaspoon) Weeks 2, 3, 4, 8 & 12. ECG and blood tests (4 ml or ¾ teaspoon) Every 3 months for up to 5 years. .

Official Title
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Novel Off-label Use of Desipramine in Infantile Neuroaxonal Dystrophy: Targeting the Sphingolipid Metabolism Pathway to Reduce Accumulation of Ceramide.

Conditions
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Infantile Neuroaxonal Dystrophy

Intervention / Treatment
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* Drug: Desipramine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 03-17years. Any gender Confirmed homozygotes or compound heterozygotes of pathogenic mutation variant(s) in PLA2G6 Confirmed homozygotes of pathogenic mutation in PLA2G6 Documentation of clinical presentation (signs and symptoms of neurodegenerative process) of INAD Exclusion Criteria: Patient has sign and symptom suggesting an ongoing acute or chronic illness such as fever of unknown origin or infection. Patient has a second genetic condition Parents are unable or unwilling to return for continued care for up to 12 months

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Children with INAD<br>Infantile neuroaxonal dystrophy (INAD) is an extremely rare autosomal recessive neurodegenerative disorder that has grave clinical outcome and significant morbidity and mortality. | Drug: Desipramine<br>* Study drug (desipramine) provided in tablet form to be taken daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Gross Motor Function as Measured by Gross Motor Function Measure (GMFM-66) | The Gross Motor Function Measure (GMFM-66) is a 66 item standardized observational instrument designed and validated to measure change in gross motor function over time in children with cerebral palsy. Items are ordered in terms of difficulty and a unit of change has the same meaning throughout the scale ranging from 0 to 100. 0 = does not initiate, 1 = initiates, 2 = partially completes, 3 = completes. Scoring the GMFM-66 requires the use of a computer program called the Gross Motor Ability Estimator (GMAE). Individual item scores are entered and a mathematical algorithm calculates an interval level total score. The total score is an estimate of the child's gross motor function. | Baseline, 3, 6, 9, and 12 months | 
| Change in Motor Function as Measured by Quick Motor Function Test (QMFT) | The Quick Motor Function Test (QMFT) is a 16 item, psychometrically robust outcome assessment, validated in children and adults with Pompe disease (a lysosomal storage disorder characterized by progressive muscle weakness). This motor function test observes performance and scores the items separately on a 5-point ordinal scale (ranging from 0 to 4). If items can be performed on both left and right extremities, the right side is taken. A total score is obtained by adding the scores of all items. The total score ranges between 0 and 64 points. A higher score correlates with greater motor function. | Baseline, 3, 6, 9, and 12 months | 
| Change in Cognitive Function as Measured by the Vineland Adaptive Behavioral Scale | The Vineland-3 is a standardized measure of adaptive behavior--the things that people do to function in their everyday lives. It is a norm-based instrument that compares the examinee's adaptive functioning in four domains: Communication, Daily Living Skills, Socialization and Motor Skills to that of others of the same age. A composite score of adaptive behavior is calculated that summarizes the individual's performance across all four domains. | Baseline, 3, 6, 9, and 12 months | 
| Number of Participants With Change in Q-T Interval on ECG | Evidence of ECG changes, specifically, prolonged Q-T interval in response to study drug. The Q-T interval is the time from the start of the Q wave to the end of the T wave. It represents the time taken for ventricular depolarisation and repolarisation, effectively the period of ventricular systole from ventricular isovolumetric contraction to isovolumetric relaxation. Participants with a prolonged Q-T interval at any timepoint is reported. | Baseline, 3, 6, 9, and 12 months | 
| Number of Participants With Abnormal Transaminase Values | Transaminase values as measured by serum alanine transaminase (ALT) and aspartate transaminase (AST). Participants with abnormal transaminase values at any timepoint is reported. | Baseline, 3, 6, 9, and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric genetic disorder, cognitive function, neuro-muscular disorder, PLA2G6