A Study of Combination Therapy in Children With ADHD

• Sponsor: Douglas Sears
• Information provided by (Responsible Party): Douglas Sears, Sears, Douglas, M.D.

Study Description

Brief Summary:

Lack of appetite and weight loss are a common side effect of ADHD therapy with amphetamines such as methylphenidate. Lack of sufficient food intake has been shown to have negative effects on weight and height as well as learning and memory.

There is no current treatment to prevent this loss of appetite except discontinuation or reduction of the methylphenidate. Discontinuation or reduction of the drug can cause the return of ADHD symptoms.

The purpose of this study is to compare the effects, good and/or bad, of two doses of a drug, cyproheptadine, vs placebo to find out if cyproheptadine prevents the appetite suppression associated with methylphenidate.

Condition or disease	Intervention/treatment	Phase
ADHD; Attention Deficit Hyperactivity Disorder; Attention Deficit Disorder With Hyperactivity; Mental Disorders Diagnosed in Childhood; Attention Deficit and Disruptive Behavior Disorders	Drug: Methylphenidate ER; Drug: Cyproheptadine	Phase 4

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	99 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Double-Blind Placebo-Controlled Study of Combination Therapy in Children With ADHD
Study Start Date :	March 2014
Actual Primary Completion Date :	March 2015
Actual Study Completion Date :	March 2015

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Control; Methylphenidate ER QD placebo BID	Drug: Methylphenidate ER; Watson generic, starting dose 18mg QD; Other Name: Concerta
Active Comparator: Methylphenidate ER, cyproheptadine 2.5mg; Methylphenidate ER QD cyproheptadine hydrochloride 2.5mg BID	Drug: Methylphenidate ER; Watson generic, starting dose 18mg QD; Other Name: Concerta; Drug: Cyproheptadine; cyproheptadine hydrochloride; Other Name: Periactin
Active Comparator: Methylphenidate ER, cyproheptadine 5mg; Methylphenidate ER QD cyproheptadine hydrochloride 5.0mg BID	Drug: Methylphenidate ER; Watson generic, starting dose 18mg QD; Other Name: Concerta; Drug: Cyproheptadine; cyproheptadine hydrochloride; Other Name: Periactin

Outcome Measures

Primary Outcome Measures :

1. Appetite - Appetite and Dietary Assessment Tool (ADAT) developed by Burrowes et al (1996) [ Time Frame: 0, 12 weeks ]

Secondary Outcome Measures :

1. Swanson, Nolan & Pelham Rating Scale - Revised (SNAP-IV): ADHD Combined Score [ Time Frame: 0,1,5,9,12 weeks ]
   The items from the DSM-IV (1994) criteria for Attention-Deficit/Hyperactivity Disorder (ADHD) are included for the two subsets of symptoms: inattention (items #1-#9) and hyperactivity/ impulsivity (items #11-#19).
2. Weight [ Time Frame: 0,1,5,9,12 Weeks ]
3. Appetite - VAS - Visual Analogue Scale [ Time Frame: 0,1,5,9,12 ]
4. Clinical Global Impressions - Improvement(CGI-I): ADHD Score [ Time Frame: 1,5,9,12 weeks ]
5. Clinical Global Impressions - Severity(CGI-S): ADHD Score [ Time Frame: 0,1,5,9,12 ]
6. Clinical Global Impressions - Effectiveness(CGI-E): ADHD Score [ Time Frame: 1,5,9,12 ]
7. Appetite - Appetite and Dietary Assessment Tool (ADAT) developed by Burrowes et al (1996) [ Time Frame: 1,5,9 weeks ]

Eligibility Criteria

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Ages Eligible for Study:	6 Years to 12 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• The subject and subject's parents speak English
• Child or adolescent patients, male or female outpatients, who are at least 6 years of age, but must not yet have reached their 13th birthday prior to Visit 1, when informed consent is obtained
• Patients must meet Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) diagnostic criteria for ADHD (any subtype) and score at least 1.5 standard deviations above the age norm for their diagnostic subtype using published norms for the Swanson, Nolan and Pelham Questionnaire: Attention-Deficit/Hyperactivity Disorder Subscale (SNAP-IV ADHD Subscale) score at both Visit 1 and 2
• Laboratory results, including serum chemistries, hematology, and urinalysis, must show no clinically significant abnormalities (clinically significant is defined as laboratory values requiring acute medical intervention, indicating a serious medical illness, or requiring further medical evaluation in the judgment of the investigator)
• Patients and parents have been judged by the investigator to be reliable to keep appointments for clinic visits and all tests, including venipuncture, and examinations required by the protocol.
• Patient has not been on stimulants for at least 2 weeks.

Exclusion Criteria:

• Patients who have a documented history of Bipolar I or II disorder, or any history of psychosis. Diabetic patients or patients on chronic steroids.
• Patients with a history of any seizure disorder (other than febrile seizures) or patients who have taken (or are currently taking) anticonvulsants for seizure control are not eligible to participate
• Patients at serious suicidal risk as defined by 1) suicidal ideation as endorsed on items 4 and 5 of the C-SSRS within the past year, 2) suicidal behaviors detected by the C-SSRS during the past two years; or 3) psychiatric interview and examination
• Patients with significant cardiovascular disease or other conditions that could be aggravated by an increased heart rate or increased blood pressure
• Patients who have any medical condition that would increase sympathetic nervous system activity markedly (for example, catecholamine-secreting neural tumor), or who are taking a medication on a daily basis (for example, albuterol, inhalation aerosols, pseudoephedrine), that has sympathomimetic activity. Such medications can be taken on an as-needed basis
• Presence of contraindications for methylphenidate or cyproheptadine hydrochloride
• Patients who have had prior serious adverse reaction to stimulants.
• Parental or (immediate) family history of substance abuse

Contacts and Locations

Locations

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United States, California
SMRI (Schuster Medical Research Institute)
Van Nuys, California, United States, 91403

Sponsors and Collaborators

Douglas Sears

Investigators

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Principal Investigator:	Jose M Schuster, MD	SMRI

More Information

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Responsible Party:	Douglas Sears, Douglas Sears, MD, Sears, Douglas, M.D.
ClinicalTrials.gov Identifier:	NCT01940978 History of Changes
Other Study ID Numbers:	001
First Posted:	September 12, 2013
Last Update Posted:	April 10, 2015
Last Verified:	April 2015

Keywords provided by Douglas Sears, Sears, Douglas, M.D.:

Methamphetamine; Methylphenidate; ADHD

Additional relevant MeSH terms:

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Disease; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Mental Disorders; Psychotic Disorders; Problem Behavior; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Pathologic Processes; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Schizophrenia Spectrum and Other Psychotic Disorders; Behavioral Symptoms	Methylphenidate; Cyproheptadine; Central Nervous System Stimulants; Physiological Effects of Drugs; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Neurotransmitter Agents; Antipruritics; Dermatologic Agents; Gastrointestinal Agents; Histamine H1 Antagonists; Histamine Antagonists