TREAT: Treatment of Children With ADHD Who do Not Fully Respond to Stimulants

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00279409
• Collaborator: National Institute of Mental Health (NIMH) (NIH), Bristol-Myers Squibb (Industry), Otsuka Pharmaceutical Co., Ltd. (Industry)
• Enrollment: 10
• Location: 1
• Arms: 2
• Duration (Months): 31.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this pilot is to initiate a program of research into the development of effective medication techniques to treat those children with ADHD who are referred because they are "partial" or "non-responders" to standard stimulant treatment.

Condition or Disease	Intervention/Treatment	Phase
Attention Deficit Hyperactivity Disorder	Drug: aripiprazole; Drug: Sugar pill	Phase 2

Detailed Description

We propose to do this with a single site, ten week, pilot study of 40 school age children, ages 6-17, with Attention-Deficit/ Hyperactivity Disorder (ADHD) and moderate or greater impairment (C-GAS < 55) who show ADHD symptoms despite a trial in the community with their primary care practitioner with either of two of the most commonly used stimulants (i.e., either OROS-MPH (Concerta) or mixed salts of amphetamine (Adderall-XR)).

These children first will be classified into three groups: Group 1, those who had been treated with a maximal dose of stimulant with partial or no response; Group 2, those treated with a suboptimal dose of stimulant and showing partial or no response, and Group 3, those who developed side effects that limited continued treatment with optimal doses of a stimulant.

The next step will be to enter these children into an open, two week trial to confirm their treatment resistance. Group 2, those treated with suboptimal doses, will have the dosage increased to the maximum recommended stimulant dose. Group 1, those who had been treated for 4 weeks with maximal doses of a stimulant, or Group 3, those who developed moderate to severe drug-related side effects, will be switched to the other class of stimulant for a two week trial, unless they have been tried on both classes. Those children will be maintained on their current class of stimulant for two weeks. At the end of the two weeks, all children will be rated on the ADHD-IV-RS by the Study Doctor. Those who have shown moderate to severe side effects or those who respond will exit the trial and be treated openly. Children from Group 2 who continue to show no improvement after a week will switch to the other stimulant. All children from Group 2 tried on both stimulants and all children from Groups 1 and 3 who continue to show mean scores greater than 1 SD over the mean for age will be referred to Phase 2.

During phase 2, they will be randomized to one of two treatment arms for eight weeks. The first treatment arm, the "simple treatment" arm, will consist of parent training plus continued treatment with a stimulant that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response, plus a placebo matching aripiprazole. The second treatment arm, called the "combination" arm, will consist of parent training plus continued treatment on stimulant plus augmentation with a second generation antipsychotic (aripiprazole). Aripiprazole (Abilify™ ) is a product that is FDA-approved and marketed for the treatment of schizophrenia and for the treatment of acute manic episodes associated with Bipolar I Disorder in adults only. However, aripiprazole is also used to treat children and adolescents with aggressive and oppositional disorders in standard clinical practice. We will continue randomizing patients until we have 40 children with ADHD become eligible to enter Phase 2.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Developing More Efficacious Treatments for Children With ADHD Who Are "Partial" or "Non-responders" to Stimulants
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: aripiprazole This treatment arm (also called the "combination arm") consists of parent training plus continued treatment on a stimulant (that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response), plus augmentation with aripiprazole. Aripiprazole pills are taken once daily over a period of 8 weeks, with patients evaluated on a weekly basis. Dosing will start at 2.5 mg and will be titrated up to 5 mg by week 1, and up to 10 mg by week 2 and for the remainder of the trial.	Drug: aripiprazole; double blind capsules (abilify or placebo) taken once daily, up to 10mg.; Other Names: Abilify
Placebo Comparator: Sugar pill This treatment arm (also called the "simple treatment" arm) will consist of parent training plus continued treatment on a stimulant (that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response), plus a placebo matching aripiprazole. Placebo pills are taken once daily over a period of 8 weeks, with patients evaluated on a weekly basis.	Drug: Sugar pill; double blind capsules (abilify or placebo) taken once daily, up to 10mg.

Outcome Measures

Primary Outcome Measures

1. ADHD Rating Scale - IV (ADHD-RS-IV) [weekly]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. English or Spanish speaking parent/guardian. Parent/guardian and child must be able to understand the protocol.

2. Primary diagnosis of ADHD despite treatment with a stimulant by the primary care treatment provider.

3. Non-responder or partial responder to stimulant treatment. ADHD symptoms and clinical impairment despite treatment with stimulant (including OROS-MPH [Concerta] or mixed salts amphetamine [Adderall]).

4. IQ of greater than 70.

5. The subject must be in school.

6. The family must be able to attend weekly visits.

Exclusion Criteria:

1. Unable to understand protocol or follow study procedures.

2. Subject doing well on stimulants.

3. Subjects showing lack of response or minimal response to stimulants due to non-compliance with taking medication or taking suboptimal doses.

4. Autism, Psychosis, Bipolar Disorder, Drug Abuse, significant suicidality, or any other psychiatric disorder (such as MDD, Anxiety Disorders, Eating Disorders) in addition to ADHD that will require treatment with additional medication or therapy.

5. The subject is using or abusing recreational drugs or has a positive urine toxicology screen (except for stimulants).

6. The subject has a history of physical, sexual, or emotional abuse that resulted in a clinically significant impact on clinical presentation, potentially driving some of the symptoms of ADHD.

7. Females who are pregnant or breast-feeding or who have a positive urine pregnancy test.

8. Sexually active females and males who do not agree to use adequate birth control.

9. Abnormal cardiac function.

10. Subject is taking prohibited concomitant medication during phase 1 or phase 2 of the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York State Psychiatric Institute	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute
• National Institute of Mental Health (NIMH)
• Bristol-Myers Squibb
• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Principal Investigator: Laurence L Greenhill, MD, New York State Psychiatric Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT00279409
• Other Study ID Numbers: 5064; P30MH071478
• First Posted: Jan 19, 2006
• Last Update Posted: Jun 19, 2020
• Last Verified: Jun 1, 2020

• Keywords provided by New York State Psychiatric Institute: Attention Deficit Hyperactivity Disorder; ADHD; Treatment resistant; Partial responder; Non-responder; Atypical Antipsychotic
• Additional relevant MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity; Aripiprazole

Study Results

Participant Flow

Arm/Group Title	Aripiprazole	Sugar Pill
Arm/Group Description	This treatment arm (also called the "combination arm") consists of parent training plus continued treatment on a stimulant (that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response), plus augmentation with aripiprazole. Aripiprazole pills are taken once daily over a period of 8 weeks, with patients evaluated on a weekly basis. Dosing will start at 2.5 mg and will be titrated up to 5 mg by week 1, and up to 10 mg by week 2 and for the remainder of the trial. aripiprazole: double blind capsules (abilify or placebo) taken once daily, up to 10mg.	This treatment arm (also called the "simple treatment" arm) will consist of parent training plus continued treatment on a stimulant (that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response), plus a placebo matching aripiprazole. Placebo pills are taken once daily over a period of 8 weeks, with patients evaluated on a weekly basis. Sugar pill: double blind capsules (abilify or placebo) taken once daily, up to 10mg.
Period Title: Overall Study
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Aripiprazole	Sugar Pill	Total
Arm/Group Description	This treatment arm (also called the "combination arm") consists of parent training plus continued treatment on a stimulant (that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response), plus augmentation with aripiprazole. Aripiprazole pills are taken once daily over a period of 8 weeks, with patients evaluated on a weekly basis. Dosing will start at 2.5 mg and will be titrated up to 5 mg by week 1, and up to 10 mg by week 2 and for the remainder of the trial. aripiprazole: double blind capsules (abilify or placebo) taken once daily, up to 10mg.	This treatment arm (also called the "simple treatment" arm) will consist of parent training plus continued treatment on a stimulant (that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response), plus a placebo matching aripiprazole. Placebo pills are taken once daily over a period of 8 weeks, with patients evaluated on a weekly basis. Sugar pill: double blind capsules (abilify or placebo) taken once daily, up to 10mg.	Total of all reporting groups
Overall Participants	0	0	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Age () []
Sex: Female, Male () []
Female
Male

Outcome Measures

1. Primary Outcome

Title	ADHD Rating Scale - IV (ADHD-RS-IV)
Time Frame	weekly

Outcome Measure Data

Analysis Population Description

Despite all efforts to contact the study team members to obtain the data, efforts were unsuccessful. No study data are available

Arm/Group Title	Aripiprazole	Sugar Pill
Arm/Group Description	This treatment arm (also called the "combination arm") consists of parent training plus continued treatment on a stimulant (that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response), plus augmentation with aripiprazole. Aripiprazole pills are taken once daily over a period of 8 weeks, with patients evaluated on a weekly basis. Dosing will start at 2.5 mg and will be titrated up to 5 mg by week 1, and up to 10 mg by week 2 and for the remainder of the trial. aripiprazole: double blind capsules (abilify or placebo) taken once daily, up to 10mg.	This treatment arm (also called the "simple treatment" arm) will consist of parent training plus continued treatment on a stimulant (that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response), plus a placebo matching aripiprazole. Placebo pills are taken once daily over a period of 8 weeks, with patients evaluated on a weekly basis. Sugar pill: double blind capsules (abilify or placebo) taken once daily, up to 10mg.
Measure Participants	0	0

Adverse Events

Time Frame	Despite all efforts to contact the study team members to obtain the data, efforts were unsuccessful. No study data are available
Adverse Event Reporting Description	Despite all efforts to contact the study team members to obtain the data, efforts were unsuccessful. No study data are available
Arm/Group Title	Aripiprazole		Sugar Pill
Arm/Group Description	This treatment arm (also called the "combination arm") consists of parent training plus continued treatment on a stimulant (that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response), plus augmentation with aripiprazole. Aripiprazole pills are taken once daily over a period of 8 weeks, with patients evaluated on a weekly basis. Dosing will start at 2.5 mg and will be titrated up to 5 mg by week 1, and up to 10 mg by week 2 and for the remainder of the trial. aripiprazole: double blind capsules (abilify or placebo) taken once daily, up to 10mg.		This treatment arm (also called the "simple treatment" arm) will consist of parent training plus continued treatment on a stimulant (that is tolerated but has not yet decreased ADHD symptoms enough to meet our criterion of response), plus a placebo matching aripiprazole. Placebo pills are taken once daily over a period of 8 weeks, with patients evaluated on a weekly basis. Sugar pill: double blind capsules (abilify or placebo) taken once daily, up to 10mg.
All Cause Mortality
	Aripiprazole		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Aripiprazole		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Aripiprazole		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

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.