Attention Deficit Disorder With HyperactivityPhase 4NCT00794625
Effectiveness of Combined Medication Treatment for Aggression in Children With Attention Deficit With Hyperactivity Disorder (The SPICY Study)
A Phase 4 study testing Valproate, Risperidone and Stimulant medication in people with Attention Deficit Disorder With Hyperactivity, run by Joseph Blader at 3 sites in United States.
Trial summary
This study will determine the advantages and disadvantages of adding one of two different types of drugs to stimulant treatment for reducing aggressive behavior in children with attention deficit with hyperactivity disorder (ADHD). Read more about this study
- Who is it for?
- Ages 6 to 12 years
- Conditions the study is for
- Attention Deficit Disorder With Hyperactivity
- What is being tested?
- Valproate, Risperidone and Stimulant medication
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 270 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2008to Apr 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Presence of ADHD
- Presence of persistent, clinically significant aggression
- Presence of ODD or CD
Who cannot join
- Presence of psychosis
- Presence of a major developmental disability
- Presence of a major mood disorder
- Contraindications to stimulant, valproate, or risperidone treatment
Trial locations and contacts
3 sites in 1 country.
United States3 sites, 3 recruiting
- Recruiting
North Shore - LIJ Health System, Zucker Hillside Hospital
Glen Oaks, New York, 11040
Ingrid S Fuentes, BA, 718-470-8487, isfuentes@nshs.edu
Allison Berest, BA, 718-470-8868, nkatsiot@nshs.edu
- Recruiting
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Candy Rhine, 210-614-7070 ext. 250, rhine@uthscsa.edu
Maria Silva, (210) 614-7070 ext. 251, maria@cgcsanantonio.org
- Recruiting
Stony Brook University Medical Center
Stony Brook, New York, 11794-8790
Lauren M Chorney, PhD, 631-632-8317, lauren.chorney@stonybrook.edu
Gabrielle A Carlson, MD, (631) 632-8842, gabrielle.carlson@stonybrook.edu
About this study
Official title: Adjunctive Treatment With Divalproex or Risperidone for Aggression Refractory to Stimulant Monotherapy Among Children With ADHD
This study will determine the advantages and disadvantages of adding one of two different types of drugs to stimulant treatment for reducing aggressive behavior in children with attention deficit with hyperactivity disorder (ADHD).
Read the detailed description
Attention deficit with hyperactivity disorder (ADHD) is a common childhood mental disorder that affects 3% to 5% of all American children. Symptoms of ADHD commonly include inability to focus or exercise normal inhibition, and in some cases, aggressive behavior. Approximately 33% to 50% of children with ADHD develop oppositional defiant disorder (ODD), and about 20% to 40% develop a conduct disorder (CD). These disorders are characterized by defiant, belligerent, and otherwise aggressive behavior. Treatment for ADHD generally includes use of stimulant medications that decrease impulsivity and increase attentiveness, such as methylphenidate (Ritalin) or dextroamphetamine (Dexedrine), but these do not always affect aggression. To treat aggression in ADHD, many physicians prescribe additional medications, including the mood stabilizing medication valproate and the antipsychotic medication risperidone.
There is no clinical evidence proving that using multiple types of medications is safe and effective. This study will treat children with ADHD and aggression with a combination of stimulants and antipsychotic or mood stabilizing medications to determine whether the aggressive behaviors and ADHD symptoms are reduced without harmful side effects.
This study has two phases. During the first phase, which will last 3 to 6 weeks, participants will be treated with normal ADHD stimulant medications. During the second phase, those whose aggressive behavior is not effectively suppressed by stimulant medication alone will then be randomly assigned to also receive valproate, risperidone, or placebo for 8 weeks. After 8 weeks, children whose aggression persists will be switched from either valproate to risperidone or risperidone to valproate for another 8 weeks. Those on placebo will not switch medications. All participants will attend weekly monitoring visits for 11 to 16 weeks over the course of the study. At these visits, aggression levels and medication side effects will be assessed. Families will also meet with the researchers to discuss the child's progress and will attend behavioral counseling with a therapist.
- Being tested
- Valproate, Risperidone, Placebo, Stimulant medication, Behavioral family counseling
- Keywords
- Attention-Deficit/Hyperactivity Disorder, Aggressive Behavior, Oppositional Defiant Disorder, Conduct Disorder
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity, Aggression, Oppositional Defiant Disorder, Conduct Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ValproateDrug
Also called Depakote, Valproic acid
Standard therapeutic doses of valproate, set according to valproic acid blood level, for 8 weeks
RisperidoneDrug
Also called Risperdal
Standard therapeutic doses of risperidone for 8 weeks
PlaceboDrug
Also called Inactive substance, "Sugar pill"
An inactive substance at identical dosing to active treatments for 8 weeks
Stimulant medicationDrug
Also called Ritalin, Dexedrine
Stimulant medication standard in the care of ADHD, such as methylphenidate or dextroamphetamine
Behavioral family counselingBehavioural
Weekly behavioral counseling with a therapist
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | During Phase 1, participants will receive a stimulant medication. If they do not respond to the stimulant, they will add valproate and behavioral family counseling to their treatment during Phase 2. If they do not respond to valproate, they will be switched to risperidone. Receives: Drug: Valproate; Drug: Risperidone; Drug: Stimulant medication; Behavioral: Behavioral family counseling |
| 2 | Experimental | During Phase 1, participants will receive a stimulant medication. If they do not respond to the stimulant, they will add risperidone and behavioral family counseling to their treatment during Phase 2. If they do not respond to risperidone, they will switch to valproate. Receives: Drug: Valproate; Drug: Risperidone; Drug: Stimulant medication; Behavioral: Behavioral family counseling |
| 3 | Placebo comparator | During Phase 1, participants will receive a stimulant medication. If they do not respond to the stimulant, they will add placebo and behavioral family counseling to their treatment during Phase 2. Receives: Drug: Placebo; Drug: Stimulant medication; Behavioral: Behavioral family counseling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Aggressive behavior
Measured: Measured weekly for 11 to 16 weeks
Secondary outcomes (1)
ADHD symptoms
Measured: Measured weekly for 11 to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2008 (estimated)
- Study startNov 2008
- Primary completionNov 2012 (estimated)
- Study completionApr 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Attention Deficit Disorder With HyperactivityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 270 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Joseph Blader
- Sponsor type
- US National Institutes of Health
- Collaborators
- University of Texas, Northwell Health
- Responsible party
- Sponsor-investigator, Joseph Blader, National Institute of Mental Health (NIMH)
- Investigators
- Joseph C. Blader, PhD, MSc, Principal investigator, Stony Brook University School of Medicine, State University of New York
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00794625
- Sponsor's protocol ID
- R01MH080050
- Other IDs
- DSIR 84-CTM
- Status last verified
- Jul 2012
- First submitted
- 19 Nov 2008
- Last updated
- 16 Jul 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Blader JC, Pliszka SR, Kafantaris V, Foley CA, Carlson GA, Crowell JA, Bailey BY, Sauder C, Daviss WB, Sinha C, Matthews TL, Margulies DM. Stepped Treatment for Attention-Deficit/Hyperactivity Disorder and Aggressive Behavior: A Randomized, Controlled Trial of Adjunctive Risperidone, Divalproex Sodium, or Placebo After Stimulant Medication Optimization. J Am Acad Child Adolesc Psychiatry. 2021 Feb;60(2):236-251. doi: 10.1016/j.jaac.2019.12.009. Epub 2020 Jan 30.
PubMed 32007604Blader JC, Pliszka SR, Kafantaris V, Sauder C, Posner J, Foley CA, Carlson GA, Crowell JA, Margulies DM. Prevalence and Treatment Outcomes of Persistent Negative Mood Among Children with Attention-Deficit/Hyperactivity Disorder and Aggressive Behavior. J Child Adolesc Psychopharmacol. 2016 Mar;26(2):164-73. doi: 10.1089/cap.2015.0112. Epub 2016 Jan 8.
PubMed 26745211Blader JC, Pliszka SR, Kafantaris V, Foley CA, Crowell JA, Carlson GA, Sauder CL, Margulies DM, Sinha C, Sverd J, Matthews TL, Bailey BY, Daviss WB. Callous-unemotional traits, proactive aggression, and treatment outcomes of aggressive children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2013 Dec;52(12):1281-93. doi: 10.1016/j.jaac.2013.08.024. Epub 2013 Sep 25.
PubMed 24290461
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjunctive Treatment With Divalproex or Risperidone for Aggression Refractory to Stimulant Monotherapy Among Children With ADHD
- ClinicalTrials.gov ID
- NCT00794625
- Acronym / sponsor ID
- R01MH080050
- Keywords
- Attention-Deficit/Hyperactivity Disorder, Aggressive Behavior, Oppositional Defiant Disorder, Conduct Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 270 participants (estimated)
- Lead sponsor
- Joseph BladerUS National Institutes of Health
- Collaborators
- University of Texas, Northwell Health
- Study start
- Nov 2008
- Primary completion
- Nov 2012 (estimated)
- Study completion
- Apr 2013 (estimated)
- First posted
- 20 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will determine the advantages and disadvantages of adding one of two different types of drugs to stimulant treatment for reducing aggressive behavior in children with attention deficit with hyperactivity disorder (ADHD).
Detailed description
Attention deficit with hyperactivity disorder (ADHD) is a common childhood mental disorder that affects 3% to 5% of all American children. Symptoms of ADHD commonly include inability to focus or exercise normal inhibition, and in some cases, aggressive behavior. Approximately 33% to 50% of children with ADHD develop oppositional defiant disorder (ODD), and about 20% to 40% develop a conduct disorder (CD). These disorders are characterized by defiant, belligerent, and otherwise aggressive behavior. Treatment for ADHD generally includes use of stimulant medications that decrease impulsivity and increase attentiveness, such as methylphenidate (Ritalin) or dextroamphetamine (Dexedrine), but these do not always affect aggression. To treat aggression in ADHD, many physicians prescribe additional medications, including the mood stabilizing medication valproate and the antipsychotic medication risperidone.
There is no clinical evidence proving that using multiple types of medications is safe and effective. This study will treat children with ADHD and aggression with a combination of stimulants and antipsychotic or mood stabilizing medications to determine whether the aggressive behaviors and ADHD symptoms are reduced without harmful side effects.
This study has two phases. During the first phase, which will last 3 to 6 weeks, participants will be treated with normal ADHD stimulant medications. During the second phase, those whose aggressive behavior is not effectively suppressed by stimulant medication alone will then be randomly assigned to also receive valproate, risperidone, or placebo for 8 weeks. After 8 weeks, children whose aggression persists will be switched from either valproate to risperidone or risperidone to valproate for another 8 weeks. Those on placebo will not switch medications. All participants will attend weekly monitoring visits for 11 to 16 weeks over the course of the study. At these visits, aggression levels and medication side effects will be assessed. Families will also meet with the researchers to discuss the child's progress and will attend behavioral counseling with a therapist.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Valproate, Drug: Risperidone, Drug: Stimulant medication, Behavioral: Behavioral family counselingDuring Phase 1, participants will receive a stimulant medication. If they do not respond to the stimulant, they will add valproate and behavioral family counseling to their treatment during Phase 2. If they do not respond to valproate, they will be switched to risperidone. |
| 2 | Experimental | Drug: Valproate, Drug: Risperidone, Drug: Stimulant medication, Behavioral: Behavioral family counselingDuring Phase 1, participants will receive a stimulant medication. If they do not respond to the stimulant, they will add risperidone and behavioral family counseling to their treatment during Phase 2. If they do not respond to risperidone, they will switch to valproate. |
| 3 | Placebo comparator | Drug: Placebo, Drug: Stimulant medication, Behavioral: Behavioral family counselingDuring Phase 1, participants will receive a stimulant medication. If they do not respond to the stimulant, they will add placebo and behavioral family counseling to their treatment during Phase 2. |
Who may qualify
- Ages
- 6 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Presence of ADHD
- Presence of persistent, clinically significant aggression
- Presence of ODD or CD
Key exclusion criteria (4 listed)
- Presence of psychosis
- Presence of a major developmental disability
- Presence of a major mood disorder
- Contraindications to stimulant, valproate, or risperidone treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ValproateAlso: Depakote, Valproic acidStandard therapeutic doses of valproate, set according to valproic acid blood level, for 8 weeks | Drug | 1, 2 |
| RisperidoneAlso: RisperdalStandard therapeutic doses of risperidone for 8 weeks | Drug | 1, 2 |
| PlaceboAlso: Inactive substance, "Sugar pill"An inactive substance at identical dosing to active treatments for 8 weeks | Drug | 3 |
| Stimulant medicationAlso: Ritalin, DexedrineStimulant medication standard in the care of ADHD, such as methylphenidate or dextroamphetamine | Drug | 1, 2, 3 |
| Behavioral family counselingWeekly behavioral counseling with a therapist | Behavioural | 1, 2, 3 |
Primary outcome
Aggressive behavior
Time frame: Measured weekly for 11 to 16 weeks
1 secondary outcome
ADHD symptoms
Time frame: Measured weekly for 11 to 16 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2012.
- Derived from this study: PubMed 32007604Blader JC, Pliszka SR, Kafantaris V, Foley CA, Carlson GA, Crowell JA, Bailey BY, Sauder C, Daviss WB, Sinha C, Matthews TL, Margulies DM. Stepped Treatment for Attention-Deficit/Hyperactivity Disorder and Aggressive Behavior: A Randomized, Controlled Trial of Adjunctive Risperidone, Divalproex Sodium, or Placebo After Stimulant Medication Optimization. J Am Acad Child Adolesc Psychiatry. 2021 Feb;60(2):236-251. doi: 10.1016/j.jaac.2019.12.009. Epub 2020 Jan 30.
- Derived from this study: PubMed 26745211Blader JC, Pliszka SR, Kafantaris V, Sauder C, Posner J, Foley CA, Carlson GA, Crowell JA, Margulies DM. Prevalence and Treatment Outcomes of Persistent Negative Mood Among Children with Attention-Deficit/Hyperactivity Disorder and Aggressive Behavior. J Child Adolesc Psychopharmacol. 2016 Mar;26(2):164-73. doi: 10.1089/cap.2015.0112. Epub 2016 Jan 8.
- Derived from this study: PubMed 24290461Blader JC, Pliszka SR, Kafantaris V, Foley CA, Crowell JA, Carlson GA, Sauder CL, Margulies DM, Sinha C, Sverd J, Matthews TL, Bailey BY, Daviss WB. Callous-unemotional traits, proactive aggression, and treatment outcomes of aggressive children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2013 Dec;52(12):1281-93. doi: 10.1016/j.jaac.2013.08.024. Epub 2013 Sep 25.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph C. Blader, PhD, MSc principal investigator
Stony Brook University School of Medicine, State University of New York
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Valproate, Risperidone and Stimulant medication in people with Attention Deficit Disorder With Hyperactivity, run by Joseph Blader at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Joseph C. Blader, PhD, MSc (631-632-8317, joseph.blader@stonybrook.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Aggressive behavior (time frame: Measured weekly for 11 to 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00794625, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2012.