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.

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03726996

Enrollment

Registered

2018-11-01

Start date

2019-01-14

Completion date

2019-08-30

Last updated

2020-10-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Infantile Neuroaxonal Dystrophy

Keywords

Pediatric genetic disorder, cognitive function, neuro-muscular disorder, PLA2G6

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. .

Interventions

DRUGDesipramine

Study drug (desipramine) provided in tablet form to be taken daily.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

3 Years to 17 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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. Desipramine: Study drug (desipramine) provided in tablet form to be taken daily.	4
Total	4

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Parent's decision	2
Overall Study	Study early termination	2

Baseline characteristics

Characteristic	Children With INAD
Age, Categorical <=18 years	4 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Gross Motor Function Measure (GMFM-66)	1 units on a scale
Quick Motor Function Test (QMFT)	0 units on a scale
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	2 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) White	1 Participants
Region of Enrollment United States	4 Participants
Sex: Female, Male Female	3 Participants
Sex: Female, Male Male	1 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 4
other Total, other adverse events	0 / 4
serious Total, serious adverse events	0 / 4

Outcome results

Primary

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.