Desipramine in Infantile Neuroaxonal Dystrophy (INAD).

• ClinicalTrials.gov Identifier: NCT03726996
• Recruitment Status: Terminated
• First Posted: November 1, 2018
• Results First Posted: October 14, 2020
• Last Update Posted: October 14, 2020
• Sponsor: Duke University
• Information provided by (Responsible Party): Duke University

Tracking Information

• First Submitted Date: October 29, 2018
• First Posted Date: November 1, 2018
• Results First Submitted Date: August 13, 2020
• Results First Posted Date: October 14, 2020
• Last Update Posted Date: October 14, 2020
• Actual Study Start Date: January 14, 2019
• Actual Primary Completion Date: August 30, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 18, 2020)

• Change in Gross Motor Function as Measured by Gross Motor Function Measure (GMFM-66) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

Original Primary Outcome Measures (submitted: October 30, 2018)

• Change in gross motor function as measured by Gross Motor Function Measure (GMFM) [ Time Frame: Baseline, 3 months, 6 months, 9 months & 12 months. ]
  The Gross Motor Function Measure (GMFM) 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. SCORING KEY 0 = does not initiate

  1. = initiates
  2. = partially completes
  3. = completes
• Change in motor function as measured by Quick Motor Function Test (QMFT) [ Time Frame: Baseline, 3 months, 6 months 9 months & 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 high score correlates with greater motor function.
• Change in cognitive function as measured by the Vineland Adaptive Behavioral Scale [ Time Frame: Baseline, 3 months, 6 months, 9 months & 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 to that of others his or her age.
• Number of Participants with Change in Q-T interval on ECG. [ Time Frame: Baseline, 3 months, 6 months, 9 months & 12 months ]
  Evidence of ECG changes, specifically, prolonged Q-T interval in response to study drug.
• Number of Participants With Abnormal Transaminase Values [ Time Frame: Baseline, 3 months, 6 months, 9 months & 12 months ]
  Change in transaminase values as measured by serum alanine transaminase (ALT) and aspartate transaminase (AST)

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Infantile Neuroaxonal Dystrophy

Intervention

Drug: Desipramine

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

Study Arms

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.

Intervention: Drug: Desipramine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: October 21, 2019): 4
• Original Estimated Enrollment (submitted: October 30, 2018): 3
• Actual Study Completion Date: August 30, 2019
• Actual Primary Completion Date: August 30, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03726996
• Other Study ID Numbers: Pro00100799
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Duke University
• Original Responsible Party: Yong-Hui Jiang, Duke University, Professor of Pediatrics
• Current Study Sponsor: Duke University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Duke University
• Verification Date: August 2020