Trial Outcomes & Findings for Effects of Methylphenidate on Cellular Abnormalities in Children With Attention Deficit Hyperactivity Disorder (ADHD) (NCT NCT00409708)
NCT ID: NCT00409708
Last Updated: 2011-05-17
Results Overview
The number of chromosomal aberrations per 100 cells excluding gaps at Baseline (n=33, n=32) and at Week 12 (n=33, n=32) was counted in blood samples cultured for 48 hours using a standard protocol. The types of abnormalities included translocations (reciprocal and non-reciprocal), insertions, dicentrics, fragments, inversions, chromatid exchanges (quadriradials and triradials), breaks, and other unusual observations, eg, aneuploidy, tetraploidy or endoreduplication.
COMPLETED
PHASE2
142 participants
baseline and at end of treatment (Week 12)
2011-05-17
Participant Flow
Participant milestones
| Measure |
Ritalin LA Plus Behavior Therapy
10-60 mg/day
|
Behavior Therapy
0 mg/day Ritalin LA
|
|---|---|---|
|
Treatment
STARTED
|
53
|
56
|
|
Treatment
COMPLETED
|
38
|
39
|
|
Treatment
NOT COMPLETED
|
15
|
17
|
|
Washout
STARTED
|
38
|
39
|
|
Washout
COMPLETED
|
17
|
29
|
|
Washout
NOT COMPLETED
|
21
|
10
|
Reasons for withdrawal
| Measure |
Ritalin LA Plus Behavior Therapy
10-60 mg/day
|
Behavior Therapy
0 mg/day Ritalin LA
|
|---|---|---|
|
Treatment
Abnormal test procedure result(s)
|
1
|
0
|
|
Treatment
Lack of Efficacy
|
0
|
1
|
|
Treatment
Protocol Violation
|
6
|
2
|
|
Treatment
Withdrawal by Subject
|
3
|
8
|
|
Treatment
Lost to Follow-up
|
0
|
6
|
|
Treatment
Administrative problems
|
5
|
0
|
|
Washout
Lack of Efficacy
|
9
|
1
|
|
Washout
Protocol Violation
|
0
|
1
|
|
Washout
Withdrawal by Subject
|
11
|
5
|
|
Washout
Lost to Follow-up
|
1
|
3
|
Baseline Characteristics
Effects of Methylphenidate on Cellular Abnormalities in Children With Attention Deficit Hyperactivity Disorder (ADHD)
Baseline characteristics by cohort
| Measure |
Ritalin LA Plus Behavior Therapy
n=52 Participants
10-60 mg/day
|
Behavior Therapy
n=52 Participants
0 mg/day Ritalin LA
|
Total
n=104 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
52 Participants
n=99 Participants
|
52 Participants
n=107 Participants
|
104 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age Continuous
|
8.3 years
STANDARD_DEVIATION 1.75 • n=99 Participants
|
8.5 years
STANDARD_DEVIATION 1.91 • n=107 Participants
|
8.4 years
STANDARD_DEVIATION 1.83 • n=206 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
38 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=99 Participants
|
35 Participants
n=107 Participants
|
66 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: baseline and at end of treatment (Week 12)Population: Per-Protocol-1 (PP1) population: The PP1 population consisted of all patients who were randomized and provided cytogenetic data for at least one of the primary endpoints at baseline and at the Week 12 evaluation.
The number of chromosomal aberrations per 100 cells excluding gaps at Baseline (n=33, n=32) and at Week 12 (n=33, n=32) was counted in blood samples cultured for 48 hours using a standard protocol. The types of abnormalities included translocations (reciprocal and non-reciprocal), insertions, dicentrics, fragments, inversions, chromatid exchanges (quadriradials and triradials), breaks, and other unusual observations, eg, aneuploidy, tetraploidy or endoreduplication.
Outcome measures
| Measure |
Ritalin LA Plus Behavior Therapy
n=36 Participants
10-60 mg/day
|
Behavior Therapy
n=35 Participants
0 mg/day Ritalin LA
|
|---|---|---|
|
The Number of Chromosomal Aberrations Per 100 Cells Excluding Gaps at Baseline and at the End of Treatment i.e Day 84 (Week 12)
Baseline
|
1.05 number of abnormalities
Standard Deviation 1.246
|
0.75 number of abnormalities
Standard Deviation 1.008
|
|
The Number of Chromosomal Aberrations Per 100 Cells Excluding Gaps at Baseline and at the End of Treatment i.e Day 84 (Week 12)
At the end of treatment i.e. week12: Mean
|
0.53 number of abnormalities
Standard Deviation 1.132
|
0.41 number of abnormalities
Standard Deviation 0.665
|
PRIMARY outcome
Timeframe: baseline and at end of treatment (Week 12)The number of micronuclei per 1000 binucleated cells was measured at Baseline ( n=34 , n=29 ) and at the end of treatment, Week 12 (n =34, n= 29), in blood cultured for 48 hours using a standard protocol.
Outcome measures
| Measure |
Ritalin LA Plus Behavior Therapy
n=36 Participants
10-60 mg/day
|
Behavior Therapy
n=35 Participants
0 mg/day Ritalin LA
|
|---|---|---|
|
The Number of Micronuclei Per 1000 Binucleated Cells Endpoints at Baseline and at the End of Treatment i.e Day 84 (Week 12)
At Baseline
|
5.76 number of micronuclei per 1000 binucleat
Standard Deviation 2.336
|
5.71 number of micronuclei per 1000 binucleat
Standard Deviation 4.535
|
|
The Number of Micronuclei Per 1000 Binucleated Cells Endpoints at Baseline and at the End of Treatment i.e Day 84 (Week 12)
At the end of treatment i.e. Week 12
|
3.63 number of micronuclei per 1000 binucleat
Standard Deviation 2.053
|
4.19 number of micronuclei per 1000 binucleat
Standard Deviation 2.737
|
SECONDARY outcome
Timeframe: baseline and at end of treatment (Week 12)Population: Per-Protocol-2 population: The PP2 population consisted of all subjects who were randomized and provided at least one post-baseline efficacy assessment.
Blood collected at baseline (n=20, n=14) and at the end of treatment, Week 12, (n= 20, n= 14) was cultured for 48 hours using a standard protocol. Giemsa staining and/or fluorescent in situ hybridization (FISH) chromosome painting was done on the cells in metaphase and the number of chromatoid exchanges per cell was recorded by blinded raters.
Outcome measures
| Measure |
Ritalin LA Plus Behavior Therapy
n=38 Participants
10-60 mg/day
|
Behavior Therapy
n=37 Participants
0 mg/day Ritalin LA
|
|---|---|---|
|
Number of Sister Chromatoid Exchanges Per Cell
Baseline
|
7.807 number of sister chromatoid exchanges
Standard Deviation 0.9228
|
7.533 number of sister chromatoid exchanges
Standard Deviation 1.2160
|
|
Number of Sister Chromatoid Exchanges Per Cell
At the end of treatment i.e. Week12
|
7.213 number of sister chromatoid exchanges
Standard Deviation 1.0408
|
7.303 number of sister chromatoid exchanges
Standard Deviation 0.6165
|
SECONDARY outcome
Timeframe: End of treatment (Week 12)Since no cytogenetic effects were observed, blood samples were not analyzed for pharmacokinetics/pharmacodynamics.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to end of treatment (Week 12)Population: Per-Protocol-2 (PP2) Population: The PP2 population consisted of all subjects who were randomized and provided at least one post-baseline efficacy assessment.
Parents completed the Conners' ADHD/DSM-IV Scale for Parents (CADS-P) consisting of the ADHD Index (12 items) and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)( 18 items). Parents rated their child's behavior of the previous week from a list of common problems. When asked "How much of a problem has this been in the last week?" parents selected 0 = none, not at all, seldom, or very infrequently; 3 = very much true, or it occurs very often or frequently; or 1 or 2 for ratings in between. A score of 50 is considered normal and more than 70 markedly atypical.
Outcome measures
| Measure |
Ritalin LA Plus Behavior Therapy
n=38 Participants
10-60 mg/day
|
Behavior Therapy
n=37 Participants
0 mg/day Ritalin LA
|
|---|---|---|
|
Change From Baseline to End of Treatment (Week 12) on the Conners' ADHD/DSM-IV Scale for Parents (CADS-P)
|
-17.0 Units on a rating scale
Standard Deviation 11.23
|
-7.0 Units on a rating scale
Standard Deviation 9.97
|
SECONDARY outcome
Timeframe: From baseline to the end of treatment (Week 12)Population: Per-Protocol-2 (PP2) Population: The PP2 population consisted of all subjects who were randomized and provided at least one post-baseline efficacy assessment.
The Clinical Global Impression scale (CGI-I) is a clinician-rated instrument designed to assess the overall change of illness relative to baseline. The CGI-I consists of 7 ratings as follows: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. CGI-I assessments are relative to the patient's status at the Baseline visit.
Outcome measures
| Measure |
Ritalin LA Plus Behavior Therapy
n=38 Participants
10-60 mg/day
|
Behavior Therapy
n=37 Participants
0 mg/day Ritalin LA
|
|---|---|---|
|
Change From Baseline to the End of Treatment (Week 12) on the Global Improvement Rating of the Clinical Global Impression Scale (CGI-I)
|
1.9 Units on a rating scale
Standard Deviation 0.81
|
3.0 Units on a rating scale
Standard Deviation 0.97
|
SECONDARY outcome
Timeframe: From baseline to the end of treatment (Week 12)Population: Per-Protocol-2 (PP2) Population: The PP2 population consisted of all subjects who were randomized and provided at least one post-baseline efficacy assessment.
The Clinical Global Impression scale (CGI-S) is a clinician-rated instrument designed to assess the severity of illness. The CGI-S rating indicates illness severity at each time-point on a scale as follows: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = extremely ill. CGI-S assessments are relative to the patient's status at the Baseline visit.
Outcome measures
| Measure |
Ritalin LA Plus Behavior Therapy
n=38 Participants
10-60 mg/day
|
Behavior Therapy
n=37 Participants
0 mg/day Ritalin LA
|
|---|---|---|
|
Change From Baseline to the End of Treatment (Week 12) on the Severity of Illness Rating of the Clinical Global Impression Scale (CGI-S)
|
-1.9 Units on a rating scale
Standard Deviation 0.98
|
-0.6 Units on a rating scale
Standard Deviation 1.01
|
Adverse Events
Ritalin+Behavior
Behavior
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Ritalin+Behavior
n=52 participants at risk
Ritalin+Behavior
|
Behavior
n=52 participants at risk
Behavior
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
9.6%
5/52
|
3.8%
2/52
|
|
Gastrointestinal disorders
Vomiting
|
9.6%
5/52
|
1.9%
1/52
|
|
General disorders
Fatigue
|
7.7%
4/52
|
0.00%
0/52
|
|
General disorders
Pyrexia
|
3.8%
2/52
|
5.8%
3/52
|
|
Infections and infestations
Nasopharyngitis
|
7.7%
4/52
|
7.7%
4/52
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
11.5%
6/52
|
9.6%
5/52
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
19.2%
10/52
|
0.00%
0/52
|
|
Nervous system disorders
Headache
|
13.5%
7/52
|
1.9%
1/52
|
|
Psychiatric disorders
Initial Insomnia
|
5.8%
3/52
|
0.00%
0/52
|
|
Psychiatric disorders
Insomnia
|
9.6%
5/52
|
0.00%
0/52
|
|
Psychiatric disorders
Tearfulness
|
5.8%
3/52
|
0.00%
0/52
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.7%
4/52
|
1.9%
1/52
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER