Infantile Neuroaxonal DystrophyPhase 4NCT03726996
Desipramine in Infantile Neuroaxonal Dystrophy (INAD).
A Phase 4 study testing Desipramine in people with Infantile Neuroaxonal Dystrophy, run by Duke University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 17 years
- Conditions the study is for
- Infantile Neuroaxonal Dystrophy
- What is being tested?
- Desipramine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jan 2019to 30 Aug 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Health Center
Durham, North Carolina, 27710
About this study
Official title: 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.
Read the 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.
.
- Conditions
- Infantile Neuroaxonal Dystrophy
- Being tested
- Desipramine
- Keywords
- Pediatric genetic disorder, cognitive function, neuro-muscular disorder, PLA2G6
- Medical subject headings
- Neuroaxonal Dystrophies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DesipramineDrug
Study drug (desipramine) provided in tablet form to be taken daily.
| Study group | Role | What they receive |
|---|---|---|
| Children with INAD | Experimental | Infantile neuroaxonal dystrophy (INAD) is an extremely rare autosomal recessive neurodegenerative disorder that has grave clinical outcome and significant morbidity and mortality. Receives: Drug: Desipramine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, 3, 6, 9, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2018
- Study start14 Jan 2019
- Primary completion30 Aug 2019
- Study completion30 Aug 2019
Why it stopped: Funding exhausted
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Infantile Neuroaxonal DystrophyStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yong-hui Jiang, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03726996
- Sponsor's protocol ID
- Pro00100799
- Status last verified
- Aug 2020
- First submitted
- 29 Oct 2018
- Last updated
- 14 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Off-label Use of Desipramine in Infantile Neuroaxonal Dystrophy: Targeting the Sphingolipid Metabolism Pathway to Reduce Accumulation of Ceramide.
- ClinicalTrials.gov ID
- NCT03726996
- Acronym / sponsor ID
- Pro00100799
- Conditions
- Infantile Neuroaxonal Dystrophy
- Keywords
- Pediatric genetic disorder, cognitive function, neuro-muscular disorder, PLA2G6
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding exhausted
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- 14 Jan 2019 (actual)
- Primary completion
- 30 Aug 2019 (actual)
- Study completion
- 30 Aug 2019 (actual)
- First posted
- 1 Nov 2018 (actual)
- Results
- Posted 14 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Children with INAD | Experimental | Drug: DesipramineInfantile neuroaxonal dystrophy (INAD) is an extremely rare autosomal recessive neurodegenerative disorder that has grave clinical outcome and significant morbidity and mortality. |
Who may qualify
- Ages
- 3 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DesipramineStudy drug (desipramine) provided in tablet form to be taken daily. | Drug | Children with INAD |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Infantile Neuroaxonal Dystrophy
RecruitingObservational study
TIRCON International NBIA Registry
Neurodegeneration With Brain Iron Accumulation (NBIA), Pantothenate Kinase-associated Neurodegeneration (PKAN)
Active, not recruitingPhase 2/3
A Study to Assess Efficacy and Safety of RT001 in Subjects With Infantile Neuroaxonal Dystrophy
Infantile Neuroaxonal Dystrophy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yong-hui Jiang, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Desipramine in people with Infantile Neuroaxonal Dystrophy, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Gross Motor Function as Measured by Gross Motor Function Measure (GMFM-66) (time frame: Baseline, 3, 6, 9, and 12 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2020.