Official Title: “Clonidine in Attention Deficit Hyperactivity Disorder (ADHD) Treatment (CAT)”

The purpose of this study is to determine the safety and efficacy of clonidine alone or in combination with methylphenidate for children 7-12 years of age with attention-deficit, hyperactivity disorder.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment

This trial will compare the benefits and side effects of two medications-clonidine and methylphenidate (MPH)-used alone or in combination to treat ADHD in children. MPH is FDA-approved for the treatment of ADHD symptoms in children, and clonidine is FDA-approved for the treatment of hypertension in adults. Stimulant medications such as MPH are known to be safe and effective for the treatment of many ADHD symptoms. Such medicines, however, do not cure the condition or improve all of the symptoms of ADHD, and the long-term effectiveness of these medications is not well-known. In this study the participants will be randomly selected to receive one of four treatments: 1.) clonidine; 2.) MPH; 3.) clonidine and MPH; or 4.) a placebo (which is not an active medication, but a substance that is thought to have no biological effect). The time participation in the study is 16 weeks.

Intervention(s) in this Clinical Trial

• Drug: clonidine
  • Clonidine is FDA-approved for the treatment of hypertension in adults.
• Drug: methylphenidate
  • MPH is FDA-approved for the treatment of ADHD symptoms in children.
• Other: placebo
  • an inactive substance

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
• Active Comparator: 2
• Active Comparator: 3
• Placebo Comparator: 4

Primary Measures

• Efficacy outcome was change in score on the Conners Abbreviated Symptom Questionnaire for Teachers (ASQ-T)
  • Time Frame: at 16 weeks
    Safety Issue?: No

Secondary Measures

• the ASQ-Parent (ASQ-P) and Child Global Assessment Scales (C-GAS). Adverse events were monitored using AE logs, the Pittsburgh Side Effects Rating Scale, vital signs and electrocardiograms
  • Time Frame: at 16 weeks
    Safety Issue?: No

Inclusion Criteria:

• Children aged 7 through 12 in school.
• All subjects must meet DSM IV criteria for the diagnosis of ADHD of any subtype [21].
• Each subject must also satisfy the following criteria regarding the severity of ADHD symptoms: 1. ADHD must be viewed as clinically significant and worthy of treatment by medications as judged by the parent and the site investigator. Operationally, medication treatment will be considered indicated for any subject who has ADHD symptoms that significantly interfere with academic or social functioning and that have not improved (or are not expected to improve) sufficiently with non-pharmacological interventions (e.g., modifying the classroom environment, tutoring). 2. The site investigator's rating of global functioning on the C-GAS must yield a score of 70 or below. Scores below 70 on the C-GAS are designated as indicating abnormal function [22]. The score of 70 corresponds to the anchor point description: "Some difficulty in a single area, but generally functioning pretty well."
• Screen of Intelligence using the vocabulary and block design subtests of the Wechsler
• Intelligence Scale for Children-Third Edition indicates an estimated I.Q > 70.
• Informed consent/assent signed. We will not enroll any child who does not want to participate.
• The designated school for each subject agrees to participate in the study by completing all required questionnaires and following all specified procedures.
• The child must be able to swallow the tablets and capsules used in this study.

Exclusion Criteria:

• Subjects with tic disorder of any type or tic symptoms, a primary diagnosis of major depression, pervasive developmental disorder, autism, any psychotic disorder, and mental retardation (based on current DSM criteria) will be excluded. We will not exclude subjects with obsessive-compulsive disorder, oppositional-defiant disorder or conduct disorder.
• The presence of a known medical condition that would preclude the use of MPH or clonidine.
• Known pregnancy. A urinary pregnancy test will be performed for all menstruating female subjects. Female subjects of child bearing potential will be advised not to become pregnant. In this circumstance, study medication will be tapered and discontinued and the subject will be terminated from the study. A urinary pregnancy test will be repeated at the end of the study. Subjects who request information regarding possible birth control mechanisms will be referred to their primary care physicians.
• Known presence of impaired renal function. A routine urinalysis will be performed for each subject to exclude signs of renal failure.
• Known active cardiovascular disease/anomaly, which would be a contraindication for the use of MPH or clonidine.
• Subjects may not receive any other medication for the treatment of ADHD. Treatment with MPH or other stimulants must be discontinued for at least 2 weeks prior to enrollment and treatment with other medications to treat ADHD (e.g., antidepressants, clonidine) must be discontinued for at least 6 weeks prior to enrollment.
• Subjects may not receive any other psychotropic medication (e.g., serotonin reuptake inhibitors), anxiolytics (e.g., clonazepam) or hypnotics. Any such medication must be discontinued at least 6 weeks prior to enrollment.
• Previous use of MPH or clonidine will be permitted.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 7 Years

Maximum Age for this Clinical Trial: 12 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

Overall Clinical Trial Officials and Contacts

Floyd R. Sallee, M.D., Ph.D. Principal Investigator Children's Hospital Medical Center  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00031395

Study ID Number: R01NS39087

ClinicalTrials.gov Identifier: NCT00031395

Health Authority: United States: Federal Government