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

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

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Children With INAD
Arm/Group Description	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.
Period Title: Overall Study
Started	4
Completed	0
Not Completed	4
Reason Not Completed
Parent's decision	2
Study early termination	2

Baseline Characteristics

Arm/Group Title		Children With INAD
Arm/Group Description		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.
Overall Number of Baseline Participants		4
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants
	<=18 years	4 100.0%
	Between 18 and 65 years	0 0.0%
	>=65 years	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants
	Female	3 75.0%
	Male	1 25.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants
	Hispanic or Latino	0 0.0%
	Not Hispanic or Latino	4 100.0%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants
	American Indian or Alaska Native	0 0.0%
	Asian	2 50.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	1 25.0%
	More than one race	0 0.0%
	Unknown or Not Reported	1 25.0%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	4 participants
		4 100.0%
Gross Motor Function Measure (GMFM-66) [1] [2]; Measure Type: Number; Unit of measure: Units on a scale
	Number Analyzed	1 participants
		1
		[1] Measure Description: The GMFM-66 is a 66 item standardized observational instrument used to measure change in gross motor function over time in children. 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.; [2] Measure Analysis Population Description: Data collected on one participant.
Quick Motor Function Test (QMFT) [1] [2]; Measure Type: Number; Unit of measure: Units on a scale
	Number Analyzed	1 participants
		0
		[1] Measure Description: The 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.; [2] Measure Analysis Population Description: Data collected on one participant.

Outcome Measures

1. Primary Outcome

Title	Change in Gross Motor Function as Measured by Gross Motor Function Measure (GMFM-66)
Description	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.
Time Frame	Baseline, 3, 6, 9, and 12 months

Outcome Measure Data

Analysis Population Description

No data collected beyond baseline.

Arm/Group Title	Children With INAD
Arm/Group Description:	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.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

2. Primary Outcome

Title	Change in Motor Function as Measured by Quick Motor Function Test (QMFT)
Description	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.
Time Frame	Baseline, 3, 6, 9, and 12 months

Outcome Measure Data

Analysis Population Description

No data collected beyond baseline.

Arm/Group Title	Children With INAD
Arm/Group Description:	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.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

3. Primary Outcome

Title	Change in Cognitive Function as Measured by the Vineland Adaptive Behavioral Scale
Description	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.
Time Frame	Baseline, 3, 6, 9, and 12 months

Outcome Measure Data

Analysis Population Description

Data not collected.

Arm/Group Title	Children With INAD
Arm/Group Description:	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.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

4. Primary Outcome

Title	Number of Participants With Change in Q-T Interval on ECG
Description	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.
Time Frame	Baseline, 3, 6, 9, and 12 months

Outcome Measure Data

Analysis Population Description

No data collected beyond 6 months.

Arm/Group Title	Children With INAD
Arm/Group Description:	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.
Overall Number of Participants Analyzed	4
Measure Type: Count of Participants; Unit of Measure: Participants
	1 25.0%

5. Primary Outcome

Title	Number of Participants With Abnormal Transaminase Values
Description	Transaminase values as measured by serum alanine transaminase (ALT) and aspartate transaminase (AST). Participants with abnormal transaminase values at any timepoint is reported.
Time Frame	Baseline, 3, 6, 9, and 12 months

Outcome Measure Data

Analysis Population Description

No data collected beyond 6 months.

Arm/Group Title	Children With INAD
Arm/Group Description:	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.
Overall Number of Participants Analyzed	4
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%

Adverse Events

Time Frame	up to 7 months
Adverse Event Reporting Description	ECG and safety lab prior to initial dose, at days 3 & 7 post initial dose and after each dose change. PI assessment no less frequently than every 12 weeks.
Arm/Group Title	Children With INAD
Arm/Group Description	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.
All-Cause Mortality
	Children With INAD
	Affected / at Risk (%)
Total	0/4 (0.00%)
Serious Adverse Events
	Children With INAD
	Affected / at Risk (%)
Total	0/4 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	1%
	Children With INAD
	Affected / at Risk (%)
Total	0/4 (0.00%)

Limitations and Caveats

Early termination due to relocation of PI from our clinical study site. All assessments were halted before the end of the study. Insufficient data collected to draw any conclusions.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Yong-Hui Jiang, MD, PhD
• Organization: Yale University
• Phone: 203-785-2660
• EMail: yong-hui.jiang@yale.edu

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03726996
• Other Study ID Numbers: Pro00100799
• First Submitted: October 29, 2018
• First Posted: November 1, 2018
• Results First Submitted: August 13, 2020
• Results First Posted: October 14, 2020
• Last Update Posted: October 14, 2020