Desipramine in Infantile Neuroaxonal Dystrophy (INAD).

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

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.

Study Overview

• Status: Terminated
• Conditions: Infantile Neuroaxonal Dystrophy
• Intervention / Treatment: Drug: Desipramine

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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• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Yong-hui Jiang, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2019
• Primary Completion (Actual): August 30, 2019
• Study Completion (Actual): August 30, 2019

Study Registration Dates

• First Submitted: October 29, 2018
• First Submitted That Met QC Criteria: October 30, 2018
• First Posted (Actual): November 1, 2018

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: September 18, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: cognitive function; Pediatric genetic disorder; neuro-muscular disorder; PLA2G6
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroaxonal Dystrophies; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Tricyclic; Adrenergic Uptake Inhibitors; Desipramine
• Other Study ID Numbers: Pro00100799

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No