Desipramine in Infantile Neuroaxonal Dystrophy (INAD).

Phase 4

Terminated

Conditions: Infantile Neuroaxonal Dystrophy

Interventions: Drug: Desipramine

Registration Number: NCT03726996

Lead Sponsor: Duke University

Brief Summary: 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: 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.

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Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 4

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Children with INAD	Desipramine	Infantile neuroaxonal dystrophy (INAD) is an extremely rare autosomal recessive neurodegenerative disorder that has grave clinical outcome and significant morbidity and mortality.

Primary Outcome Measures

Name	Time	Method
Change in Gross Motor Function as Measured by Gross Motor Function Measure (GMFM-66)	Baseline, 3, 6, 9, and 12 months	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.
Change in Motor Function as Measured by Quick Motor Function Test (QMFT)	Baseline, 3, 6, 9, and 12 months	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.
Change in Cognitive Function as Measured by the Vineland Adaptive Behavioral Scale	Baseline, 3, 6, 9, and 12 months	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.
Number of Participants With Change in Q-T Interval on ECG	Baseline, 3, 6, 9, and 12 months	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.
Number of Participants With Abnormal Transaminase Values	Baseline, 3, 6, 9, and 12 months	Transaminase values as measured by serum alanine transaminase (ALT) and aspartate transaminase (AST). Participants with abnormal transaminase values at any timepoint is reported.