Clinical Trial Results:
International Study to Predict Optimized Treatment - in Attention-Deficit and Hyperactivity Disorder
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Summary
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EudraCT number |
2009-013272-47 |
Trial protocol |
NL |
Global end of trial date |
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Jun 2020
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First version publication date |
03 Jun 2020
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
iSPOT-A
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Total Brain
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Sponsor organisation address |
268 Bush Street, #2633, San Francisco, United States,
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Public contact |
Donna Palmer, Total Brain, +614 0404 861 295, donna.palmer@totalbrain.com
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Scientific contact |
Donna Palmer, Total Brain, +614 0404 861 295, donna.palmer@totalbrain.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Interim
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Date of interim/final analysis |
21 Dec 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
No
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General information about the trial
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Main objective of the trial |
The primary objectives of the iSPOT-A trial are to use Brain Resource's standardized 'Integrative Neuroscience' test batteries to 1) Identify objective markers of ADHD compared with healthy controls, using cognitive, brain and genetic markers
2) Identify objective markers that best predict treatment response (defined by active symptom remission) to methylphenidate (immediate release formulation) using cognitive, brain and genetic markers.
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Protection of trial subjects |
Site/ Data monitoring completed intermittently.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Sep 2009
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Ethical reason, Safety | ||
Long term follow-up duration |
12 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Australia: 174
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Country: Number of subjects enrolled |
United States: 354
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Country: Number of subjects enrolled |
Netherlands: 194
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Worldwide total number of subjects |
722
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EEA total number of subjects |
194
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
376
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Adolescents (12-17 years) |
346
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
ADHD Subjects: To be eligible for screening, subjects must be 6-17 years of age, must have been provided written informed consent to participate from a parent and/or legally recognized guardian, must meet the DSM-IV criteria for ADHD and must be a candidate for treatment with methylphenidate (immediate or extended release). | ||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Baseline (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Methylphenidate | ||||||||||||||||||||||||||||||
Arm description |
Short acting- Dosage: 5 mg twice daily (before breakfast and lunch) with gradual increments of 5 to 10 mg weekly. Daily dosage above 60 mg is not recommended. Long acting - Dosage: 9 to 20 mg once daily in the morning (with or without food) with gradual increments of 9 to 20 mg weekly. Daily dosage above 60 mg is not recommended. | ||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Ritalin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Short Acting Methylphenidate
Dosage: 5 mg twice daily (before breakfast and lunch) with gradual increments of 5 to 10 mg weekly. Daily dosage above 60 mg is not recommended.
Drug: Long Acting Methylphenidate
Dosage: 9 to 20 mg once daily in the morning (with or without food) with gradual increments of 9 to 20 mg weekly. Daily dosage above 60 mg is not recommended.
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Arm title
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Healthy Control | ||||||||||||||||||||||||||||||
Arm description |
Healthy Controls | ||||||||||||||||||||||||||||||
Arm type |
No intervention | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 336 ADHD subjects and 158 healthy controls have been used in primary analyses. Remaining subjects have been withheld as validation cohort in line with dialogue with the FDA. |
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Baseline characteristics reporting groups
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Reporting group title |
Baseline
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Reporting group description |
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End points reporting groups
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Reporting group title |
Methylphenidate
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Reporting group description |
Short acting- Dosage: 5 mg twice daily (before breakfast and lunch) with gradual increments of 5 to 10 mg weekly. Daily dosage above 60 mg is not recommended. Long acting - Dosage: 9 to 20 mg once daily in the morning (with or without food) with gradual increments of 9 to 20 mg weekly. Daily dosage above 60 mg is not recommended. | ||
Reporting group title |
Healthy Control
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Reporting group description |
Healthy Controls | ||
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End point title |
ADHD Rating Scale-IV [1] [2] | ||||||||||
End point description |
The primary research outcome is treatment response, defined as a ≥25% decrease from the baseline on
the 18 item ADHD Rating Scale-IV.
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End point type |
Primary
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End point timeframe |
Baseline to week 6
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No comparison arms for primary endpoint. [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint not required for Healthy Controls |
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| No statistical analyses for this end point | |||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline through to Week 52 (if completed) for each participant in first cohort.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17
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Reporting groups
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Reporting group title |
Methylphenidate
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Reporting group description |
Short acting- Dosage: 5 mg twice daily (before breakfast and lunch) with gradual increments of 5 to 10 mg weekly. Daily dosage above 60 mg is not recommended. Long acting - Dosage: 9 to 20 mg once daily in the morning (with or without food) with gradual increments of 9 to 20 mg weekly. Daily dosage above 60 mg is not recommended. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Healthy Control
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Reporting group description |
Healthy Controls | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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15 Jan 2009 |
1. Mini International Neuropsychiatric Interview (MINI Plus) replaced with Mini International Neuropsychiatric Interview for Children and Adolescents (MINI Kid) as this is more appropriate for the subject population.
2. Specific language to clarify the use of the MINI Kid to exclude subjects with pervasive developmental disorders and psychotic disorders.
3. Removal of the Clinical Global Impressions scale.
4. Conners Comprehensive Behaviour Rating Scales (CBRS) replaced with Conners Rating Scales- Revised (CRS-R).
5. Neuroticism, Extroversion and Openness Five Factor Inventory (NEO-FFI) for children replaced with Five Factor Personality Inventory – Children (FFPI-C).
6. 2nd blood draw added at week 6 visit
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10 Oct 2010 |
1. Both short acting and extended release methylphenidate can be prescribed as treatment for the study as this is common practice.
2. Informed consent may be obtained more than 48hrs prior to screening procedures.
3. Development of an Early Termination Visit to obtain as much useful information from participants as possible. Patients who early terminate from the study can still complete follow up assessments.
4. Inclusion criteria – Subjects who score at least 6 Inattentive or Hyperactive/impulsive items >1 on the Attention Deficit / Hyperactivity Disorder Rating Scale.
5. Exclusion criteria – History of brain injury details to be standardized to match the Brain Resource International Database criteria.
6. Brain Resource must be notified of any Serious Adverse Events within 24hrs of site personnel being informed of the event.
7. The inclusion of a Publication Plan as Appendix F.
8. Definition of Study Deviation and description of standard procedure once one has occurred.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
