This study will evaluate the efficacy and safety of methylphenidate for treating hyperactivity, impulsiveness, and distractibility in 60 children and adolescents with Pervasive Developmental Disorders (PDD). Methylphenidate (Ritalin)is approved by the Food and Drug Administration for the treatment of children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD). Data supporting its safety and effectiveness in treating ADHD symptoms in PDD are limited. Children and adolescents who do not show a positive response to methylphenidate will be invited to participate in a pilot study of the non-stimulant medication guanfacine (Tenex).

Condition	Treatment or Intervention
Attention Deficit Disorder with Hyperactivity Autistic Disorder Pervasive Development Disorders	Drug: methylphenidate  Drug: guanfacine

Further Study Details: 

Primary Outcomes: hyperactivity, impulsiveness, and distractibility
Expected Total Enrollment:  60

The safety and efficacy of methylphenidate (MPH) in 60 children and adolescents with PDD and behavioral difficulties (such as hyperactivity, impulsiveness and distractibility) will be evaluated in a multi-dose, 4-week randomized, crossover, placebo-controlled study. The MPH study has three parts: a Test-Dose Period, a Double-Blind trial and an 8-Week Extension Period (open-label). After a screening visit, eligible children will start a 1-week Test-Dose Period. During this week, each child will be given the three MPH doses that are used in the Double-Blind trial to make sure there are no serious side effects. If problems are encountered at the high dose level, that dose will not be given in the Double-Blind phase. The Double-Blind phase lasts 4 weeks and consists of three different MPH dose levels and a week of placebo. Each treatment/dose is given for 1 week, and neither the researcher nor the participants' families will know whether the medication is placebo or MPH. Children who do well during this phase will continue on the best dose of MPH (determined during the Double-Blind phase) for an additional eight weeks (open-label).

Those who do not show significant improvement during the Double-Blind phase, do not tolerate MPH during the Test Dose Period, or are not able to take MPH before beginning the study are offered open-label treatment with guanfacine for 8 weeks.

Prior to randomization in the MPH trial OR entry into the open-label guanfacine trial, there will be a medication-free period for children who are currently on medication. The withdrawal will be conducted in clinically appropriate way (depending on drug and duration of treatment) to minimize withdrawal effects. This period is to establish a drug-free baseline measurement and to minimize drug-drug interaction. No participant will be withdrawn from a currently effective medication.

Ages Eligible for Study:  5 Years   -   14 Years,  Genders Eligible for Study:  Both

Criteria

• Diagnosis of PDD (including Asperger's Disorder and Autistic Disorder)
• Clinically significant symptoms of ADHD
• Mental age of at least 18 months
• Blood pressure within normal ranges for age and gender
• Weight 16 kg or more
• Absence of chronic tic disorder
• Absence of any medical condition that would be incompatible with the study treatments
• Absence of evidence of hypersensitivity to study treatments

California
      UCLA Neuropsychiatric Institute, Los Angeles,  California,  90024,  United States
Connecticut
      Yale Child Study Center, New Haven,  Connecticut,  06520,  United States
Indiana
      Indiana University-Riley Hospital for Children, Indianapolis,  Indiana,  46202,  United States
Maryland
      Kennedy Krieger Institute, Baltimore,  Maryland,  21231,  United States
Ohio
      Ohio State University, Columbus,  Ohio,  43210,  United States

Study chairs or principal investigators

Eugene Arnold, MD,  Study Chair,  Ohio State University   
Larry Scahill, Ph.D,  Yale University   

Study ID Numbers:  N01MH70009-A; N01MH80011-A; N01MH70010-A; N01MH70001-A
Record last reviewed:  November 2004
Last Updated:  November 9, 2004
Record first received:  October 23, 2001
ClinicalTrials.gov Identifier:  NCT00025779
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08