Long Acting Stimulant Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in Young Children

• Sponsor: University of Nebraska (Other)
• Overall Status: Completed
• CT.gov ID: NCT00754208
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arm: 1
• Duration (Months): 15
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This is a pilot study evaluating the effectiveness, safety, and tolerability of Ritalin LA in treating Attention Deficit Hyperactivity Disorder (ADHD) in 4 and 5 year old children. Virtually no data has been published on the use of long-acting stimulant preparations in very young children despite early symptomatic development in a significant portion of young children with ADHD. This would be one of the first studies looking at a long-acting preparation of a stimulant medication in the treatment of ADHD in very young children.

Hypotheses

1. Ritalin LA is effective for the treatment of ADHD in 4 and 5 year old children.

2. Ritalin LA is reasonably well-tolerated in the treatment of ADHD in 4 and 5 year old children.

Condition or Disease	Intervention/Treatment	Phase
Attention Deficit Hyperactivity Disorder	Drug: methylphenidate	Phase 4

Detailed Description

This protocol involves an 8-week, open-label, pilot study evaluating the effectiveness, safety, and tolerability of Ritalin LA in treating Attention-Deficit/Hyperactivity Disorder (ADHD) in 4 and 5 year old children. The purpose of this study is to ascertain pilot data on the use of long-acting stimulants in preschool-age children since virtually no data exist on these medications in this population. The interventions include utilizing short-acting methylphenidate for the initial dosing and titration and then converting the children to Ritalin LA once an optimal dose has been found. Parents will also be receiving parent education training throughout the study. Evaluations will include obtaining the ADHD-IV at every visit, side effects of the medication, vital signs, EKG, physical exam, the Clinical Global Assessment Scale, and the Clinical Global Impression-Improvement and Severity Scales. This study will also assess parent stress with the Parent Stress Index and the emotional index of the children with the Expressed Emotion Scale for Children. Follow-up will be weekly during the first month and bi-weekly during the second month.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Long Acting Stimulant Treatment of ADHD in Young Children
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Other: methylpehnidate open-label treatment with methylphenidate

Drug: methylphenidate; Starting dose: methylphenidate (immediate-release pill) or Methylin (immediate-release chewable tablet for those unable to swallow pills) 2.5mg Q AM and Q noon. Target dose of 1mg/kg/day. Titration will occur as follows: 5mg Q AM and Q noon, then 7.5mg Q AM and Q noon, then 10mg Q AM and Q noon, as tolerated, not to exceed 30mg per day. Once each child arrives at a stable dose with a good response and good tolerability, they will be converted to the closest Ritalin LA dose, with a target dose of 1mg/kg/day.; Other Names: Ritalin Methylin Ritalin LA

Outcome Measures

Primary Outcome Measures

1. Change in Attention Deficit Hyperactivity Disorder Rating Scale-IV Parent Version Investigator-Scored (ADHD-IV-Parent: Inv) Total Score. [8 weeks]

   Change from baseline to endpoint of investigator-scored, parent version of the Attention Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-IV rating scale). The ADHD-IV contains 18 items, and each item is rated 0, 1, 2 or 3. Minimum score is 0. Maximum score is 54. Change in score represents the difference between the total score at end point compared to the total score at baseline.

Secondary Outcome Measures

1. Change in Clinical Global Impression-Severity [8 weeks]

   Change in global rating of severity of ADHD symptoms. CGI severity is rated on a scale of 1 to 6 (normal to severely ill; refer to description in baseline information). The change in the severity rating reflects the change in this score from baseline to endpoint.

2. Change in Children's Global Assessment Scale (CGAS) Score [8 weeks]

   This measures the change in the subject's global assessment of functioning as rated by the clinician. This Children's Global Assessment Scale (CGAS) is rated on a 0-100 scale (refer to baseline information). The change in this score is the difference between the score at baseline to end point.

3. Clinical Global Impression- Improvement [8 weeks]

   The Clinical Global Impression-Improvement scale is a measure of the clinician's assessment of the overall degree of improvement in ADHD symptoms from baseline to endpoint. The CGI-I is rated on a 1 to 6 scale, with 1=very much improved, 2=much improved, 3=minimally improved, 4= no change, 5= minimally worse, 6=much worse.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 5 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Informed consent obtained from the legal guardian.

• Parent and child must be English-speaking.

• The child must have been living with the parent or guardian for a minimum of 6 months at the time of study entry.

• Age: 4-5 years of age at study entry.

• weight of at least 15kg (20th percentile for 4 year olds) for boys and weight of at least 14.5kg (20th percentile for 4 year olds) for girls

• Severity: age and sex-adjusted T score greater or equal to 65 on the Hyperactive- Impulsive Subscale of both the Conners Parent and Teacher Rating Scales (L)

• Diagnosis: meets DSM-IV criteria for ADHD (hyperactive/impulsive or combined subtype), on Parent Diagnostic Interview Schedule for Children-IV (DISC-IV) and clinical interview by experienced clinician. ADHD must be the primary disorder.

• Duration: symptoms must have been present for a minimum of nine months.

• Impairment: less than or equal to 55 on the Child Global Assessment Scale.

• Cognitive functioning: An estimated IQ 70 or greater on the Peabody Picture Vocabulary Test (PPVT).

• School: participation in school-type program at least 2 half-days per week where class includes at least 8 peers; if child has been expelled from an eligible program in the 3 months before screening, they can be considered for enrollment as this may reflect severity of the disorder

• Parents and patients must be able to attend regular study visits.

• Children being treated with other stimulant or non-stimulant medications prior to enrollment will be allowed to discontinue treatment with these medications in order to enter the study, providing the parent wants to do so to enable their child to have a trial of Ritalin LA, the target symptoms are not well-controlled or unwanted side effects are persisting on their current treatment, and the prescribing physician is notified by the parent. These children will have a visit 1A in order to accommodate a 5 half-lives washout of their pre-study medication.

Exclusion Criteria:

• Other medications: no concurrent psychotropic medications or other medications (including herbal preparations and over-the-counter medications) with significant CNS effects (e.g., antidepressants, antipsychotics, drugs affecting blood pressure or heart rate, anticonvulsants, alpha-agonists, adrenergic blockers, lithium, or sedating antihistamines).

• General medical conditions: children with major medical conditions that would interfere with involvement in the study or the study medication will not be enrolled.

• Serious structural cardiac abnormalities: The recent joint advisory of the American Academy of Pediatrics (AAP) and the American Heart Association (AHA) recommend use of stimulant medications should generally be avoided in patients with cardiomyopathy, serious heart rhythm or structural abnormalities, or other serious cardiac problems. Any patient with such a diagnosis will not be allowed in this study.

• Systolic and diastolic blood pressure above 95th percentile for age and gender

• Exclusionary Psychiatric Conditions: Current Adjustment Disorder, Autism, Psychosis, Bipolar Disorder, PTSD, significant suicidality, or any other psychiatric disorder in addition to ADHD that requires treatment with additional medications.

• History of physical, sexual, or emotional abuse that results in a clinically significant impact on clinical presentation, potentially driving some of the symptoms of ADHD.

• Prior failure to respond to an adequate trial of any methylphenidate product. This will be at the determination of the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-5584

Sponsors and Collaborators

• University of Nebraska

Investigators

• Principal Investigator: Joan Daughton, MD, University of Nebraska

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joan Daughton, MD, Principal Investigator, University of Nebraska
• ClinicalTrials.gov Identifier: NCT00754208
• Other Study ID Numbers: 380-08
• First Posted: Sep 17, 2008
• Last Update Posted: Feb 22, 2018
• Last Verified: Feb 1, 2018

• Keywords provided by Joan Daughton, MD, Principal Investigator, University of Nebraska: Attention Deficit Hyperactivity Disorder; Stimulant Treatment; Young Children
• Additional relevant MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity; Methylphenidate

Study Results

Participant Flow

Recruitment Details	Recruitment occurred from September 2008 through Deceber 2009 in an academic medical center.
Pre-assignment Detail	Please see inclusion and exclusion criteria.

Arm/Group Title	Ritalin LA for ADHD
Arm/Group Description	Subjects treated with Ritalin LA for ADHD
Period Title: Overall Study
STARTED	7
COMPLETED	7
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Ritalin LA for ADHD
Arm/Group Description	4 and 5 year old subjects with ADHD
Overall Participants	7
Age (Count of Participants)
<=18 years	7 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	4
Sex: Female, Male (Count of Participants)
Female	1 14.3%
Male	6 85.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	7 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	7 100%
ADHD Subtype (Count of Participants)
ADHD, combined subtype	7 100%
ADHD, inattentive subtype	0 0%
ADHD, hyperactive/impulsive subtype	0 0%
Comorbid Oppositional Defiant Disorder (Count of Participants)
YES	4 57.1%
NO	3 42.9%
Prior Treatment (Count of Participants)
Individual therapy	2 28.6%
Pharmacotherapy	0 0%
No prior treatment	5 71.4%
Clinical Global Impression-Severity Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.14 (0.69)
Children's Global Assessment Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	49.9 (2.04)

Outcome Measures

1. Primary Outcome

Title	Change in Attention Deficit Hyperactivity Disorder Rating Scale-IV Parent Version Investigator-Scored (ADHD-IV-Parent: Inv) Total Score.
Description	Change from baseline to endpoint of investigator-scored, parent version of the Attention Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-IV rating scale). The ADHD-IV contains 18 items, and each item is rated 0, 1, 2 or 3. Minimum score is 0. Maximum score is 54. Change in score represents the difference between the total score at end point compared to the total score at baseline.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1
Arm/Group Description	All subjects treated with open-label methylphenidate (Ritalin LA)
Measure Participants	7
Mean (Standard Deviation) [units on a scale]	-20.1 (13.87)

2. Secondary Outcome

Title	Change in Clinical Global Impression-Severity
Description	Change in global rating of severity of ADHD symptoms. CGI severity is rated on a scale of 1 to 6 (normal to severely ill; refer to description in baseline information). The change in the severity rating reflects the change in this score from baseline to endpoint.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1
Arm/Group Description	All subjects treated with open-label methylphenidate
Measure Participants	7
Mean (Standard Deviation) [units on a scale]	-2.4 (1.72)

3. Secondary Outcome

Title	Change in Children's Global Assessment Scale (CGAS) Score
Description	This measures the change in the subject's global assessment of functioning as rated by the clinician. This Children's Global Assessment Scale (CGAS) is rated on a 0-100 scale (refer to baseline information). The change in this score is the difference between the score at baseline to end point.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1
Arm/Group Description	All subjects treated with open-label methylphenidate
Measure Participants	7
Mean (Standard Deviation) [units on a scale]	9.9 (6.07)

4. Secondary Outcome

Title	Clinical Global Impression- Improvement
Description	The Clinical Global Impression-Improvement scale is a measure of the clinician's assessment of the overall degree of improvement in ADHD symptoms from baseline to endpoint. The CGI-I is rated on a 1 to 6 scale, with 1=very much improved, 2=much improved, 3=minimally improved, 4= no change, 5= minimally worse, 6=much worse.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1
Arm/Group Description	All subjects treated with open-label methylphenidate
Measure Participants	7
Very Much Improved	3 42.9%
Much Improved	2 28.6%
Minimally Improved	1 14.3%
No Change	1 14.3%
Minimally Worse	0 0%
Much Worse	0 0%

Adverse Events

Time Frame	8 weeks
Adverse Event Reporting Description	Adverse events were collected by spontaneous report
Arm/Group Title	Methylpehnidate
Arm/Group Description	open-label treatment with methylphenidate methylphenidate: Starting dose: methylphenidate (immediate-release pill) or Methylin (immediate-release chewable tablet for those unable to swallow pills) 2.5mg Q AM and Q noon. Target dose of 1mg/kg/day. Titration will occur as follows: 5mg Q AM and Q noon, then 7.5mg Q AM and Q noon, then 10mg Q AM and Q noon, as tolerated, not to exceed 30mg per day. Once each child arrives at a stable dose with a good response and good tolerability, they will be converted to the closest Ritalin LA dose, with a target dose of 1mg/kg/day.
All Cause Mortality
	Methylpehnidate
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Serious Adverse Events
	Methylpehnidate
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Other (Not Including Serious) Adverse Events
	Methylpehnidate
	Affected / at Risk (%)	# Events
Total	7/7 (100%)
Gastrointestinal disorders
Decreased Appetite	3/7 (42.9%)	3
Nausea	1/7 (14.3%)	1
General disorders
Irritability	2/7 (28.6%)	2
Nail biting	1/7 (14.3%)	1
Nervous system disorders
Tics	1/7 (14.3%)	2

Limitations/Caveats

This study is limited by a small sample size and open-label design.

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.