Psychotic DisordersPhase 4IMPACTNCT00806234
Reducing Weight Gain and Improving Metabolic Function in Children Being Treated With Antipsychotics
A Phase 4 study testing Aripiprazole or Perphenazine, Metformin and Olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine in people with Psychotic Disorders, run by Johns Hopkins University at 4 sites in United States.
Trial summary
This study will test the effectiveness of two different treatments for children and adolescents who have gained weight on their antipsychotic medications. Read more about this study
- Who is it for?
- Ages 8 to 19 years
- Conditions the study is for
- Psychotic Disorders
- What is being tested?
- Aripiprazole or Perphenazine, Metformin and Olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 127 participants
- Where
- 4 sitesUnited States
- Study dates
- Jan 2009to Mar 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 8 to 19 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- DSM diagnoses that have an FDA indication for atypical antipsychotic use for at least one agent in the respective pediatric or adult age group. Specifically, primary DSM-IV diagnosis of Early Onset Schizophrenia Spectrum (EOSS; schizophrenia, schizoaffective disorder, schizophreniform disorder, psychotic disorder NOS); Bipolar Spectrum (bipolar I, II and NOS); Major depressive disorder with psychosis; Mood disorder NOS corresponding to Leibenluft and colleagues severely mood dysregulated (SMD) broad spectrum bipolar disorder; Mood disorder NOS corresponding to irritability associated with autism spectrum disorders; or - for adult teen participants aged 18-19 years - Major depressive disorder. Diagnoses will be determined by clinical interview, Leibenluft's modification of the K-SADS-PL, and the "Aberrant Behavior Checklist" (cutoff score of 18, as used by FDA for approval of risperidone and aripiprazole in minors).
- Clinically stable on current treatment regimen for at least 30 days, as assessed in a three-step process
- Current SGA treatment with olanzapine, quetiapine, risperidone, ziprasidone aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine for ≥ 8 weeks
- Stable dose of current SGA and psychotropic co-medications for at least 30 days
- Body mass index (BMI) at least in the 85th percentile for age and gender
- Substantial weight gain over the previous 3 years while taking a SGA, as reflected by family and referring physician's judgment. The weight gain did not have to occur on the child's current SGA. Weight needs to have remained stable or increased over past year.
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- Agrees to use two effective forms of birth control or to remain abstinent
- Has a primary caretaker who has known the child well for at least 6 months before study entry
- Primary caretaker is able to participate in study appointments as clinically indicated
Who cannot join
- Treatment with any medication (other than the currently prescribed psychotropic medications) that would significantly alter glucose, insulin, or lipid levels. Exception: orlistat and amantadine are permitted if the individual has taken the drug for at least one year without weight loss.
- Major neurological or medical illness that affects weight gain or that would prevent participation in physical activities
- Fasting glucose levels indicating need for prompt treatment
- Pediatrician or pediatric gastroenterologist recommendation to address abnormal fasting labs by pursuing more active treatment than those in the 2007 American Medical Association guidelines
- Diagnosis of anorexia nervosa or bulimia nervosa, as based on current or lifetime DSM-IV criteria
- Diagnosis of substance dependence disorder (other than tobacco dependence) within the past month, as based on DSM-IV criteria
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- Positive urine toxicology indicating ongoing use of illicit substance
- Current treatment with more than one antipsychotic medication
- Current treatment with more than 3 total psychotropic medications (i.e., 2 psychotropics plus SGA), with the exception of subjects taking 2 medications for ADHD in which a total of 4 psychotropic medications are allowed.
- Known hypersensitivity to metformin
- Prior treatment with aripiprazole and perphenazine for more than 2 weeks that was stopped for inefficacy or intolerability
- Pregnant, breastfeeding, or unwilling to comply with contraceptive requirements of study
- IQ score less than 55
- Significant risk of dangerousness to self or to others that would make study participation inadvisable
- Language issues that prevent child and/or parent from completing assessments or treatment
- Ongoing or previously undisclosed child abuse requiring new department of social service intervention
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Maryland
Baltimore, Maryland, 21201
Johns Hopkins Hospital
Baltimore, Maryland, 21205
University of North Carolina, Division of Child and Adolescent Psychiatry
Chapel Hill, North Carolina, 27599
The Zucker Hillside Hospital
Glen Oaks, New York, 11004
About this study
Official title: Improving Metabolic Parameters of Antipsychotic Child Treatment (IMPACT)
This study will test the effectiveness of two different treatments for children and adolescents who have gained weight on their antipsychotic medications.
Read the detailed description
Disorders that involve severe dysregulation of mood or thoughts in children -- such as early onset bipolar spectrum (BPS) and schizophrenia spectrum (SS) disorders -- are commonly treated with antipsychotic medications. However, many of the newest and most commonly prescribed antipsychotic medications can cause weight gain and metabolic dysfunctions. Use of these newer antipsychotics, called second generation antipsychotics (SGAs), is increasing rapidly in children, and the risk of weight gain from SGAs is higher among children than adults. Excessive weight gain can lead to obesity, which, in turn, can lead to increased health care costs, increased risk of sickness, and lower life expectancy. These factors are enhanced in children and adolescents who grow up obese.
Two different strategies to reduce weight gain and metabolic side effects from SGAs will be tested in this study. The first strategy involves switching from the current SGA to a lower risk agent (aripiprazole or perphenazine) hypothesized to result in weight loss and improved metabolic functioning. The second strategy involves taking the medication metformin in addition to the current SGA. Metformin is approved by the Food and Drug Administration (FDA) to promote weight loss in youth with diabetes and has been effective in reducing weight in youth taking SGAs.
Participation in this study will last between 26 and 27 weeks and will be divided into two parts. The first part will last 2 to 3 weeks and include three study visits. During this part, participants will undergo a physical exam, an electrocardiogram (EKG), a dual energy X-ray absorptiometry (DXA) test, and blood tests. The DXA measures body fat.
The second part will last 24 weeks and include nine study visits. During this part, participants will be randomly assigned to one of three conditions: gradual switch of current SGA medication to either aripiprazole or perphenazine, addition of metformin to current SGA medication, or no change to treatment with current SGA medication. Visits will take place on Weeks 1, 2, 4, 6, 8, 12, 16, 20, and 24. At each visit, participants will meet with a study doctor who will assess symptoms and side effects, and participants and their guardians will receive information and recommendations about childhood obesity and weight loss. There will also be monthly urine pregnancy tests, and two blood tests.
- Conditions
- Psychotic Disorders
- Being tested
- Aripiprazole or Perphenazine, Metformin, Olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine
- Keywords
- Weight Gain, Obesity, IMPACT, Antipsychotic Treatment, Excessive Weight Gain Associated With Antipsychotic Treatment, Hybrid Efficacy/Effectiveness Design, Reducing Weight Gain, Improving Metabolic Parameters, Aripiprazole, Metformin, Risperdal, Seroquel, Quetiapine, Olanzapine, Zyprexa, Geodon, Risperidone, Abilify, Trilafon, Perphenazine
- Medical subject headings
- Psychotic Disorders, Weight Gain, Obesity, Tooth, Impacted
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aripiprazole or PerphenazineDrug
Also called Abilify, Trilafon
Baseline second generation antipsychotic (SGA) treatment will be gradually decreased and discontinued over 8 weeks while treatment with aripiprazole or perphenazine will be increased to effective levels.
MetforminDrug
Also called Glucophage
Metformin treatment will be added to current SGA treatment, with dosing based on participant weight and increased according to a preset titration schedule unless side effects interfere.
Olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetineDrug
Also called Zyprexa, Seroquel, Risperdal, Geodon, Abilify, Saphris, Sycrest, Fanapt, Fanapta, Zomaril, Latuda, Invega, Symbyax
Current antipsychotic medication will be continued throughout the treatment period, with changes in dose only made as clinically indicated
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Participants will continue on current antipsychotic medication. Receives: Drug: Olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine |
| 2 | Experimental | Participants will undergo a staggered switch from current antipsychotic medication to aripiprazole or perphenazine. Receives: Drug: Aripiprazole or Perphenazine |
| 3 | Experimental | Participants will add metformin to current antipsychotic medication treatment. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Body Mass Index (BMI) Z-score Change
Measured: Change from baseline to 24 weeks
Secondary outcomes (3)
Change in Whole Body Insulin Sensitivity Index
Measured: Change from baseline to 24 weeks
Triglyceride Levels
Measured: Change from baseline to 24 weeks
Change in Low Density Lipoprotein (LDL) Cholesterol Level
Measured: From Baseline to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2008 (estimated)
- Study startJan 2009
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Psychotic DisordersStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- 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
- Factorial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), University of Maryland, University of North Carolina, Chapel Hill, The Zucker Hillside Hospital
- Responsible party
- Principal investigator, Mark Riddle, MD, Johns Hopkins University
- Investigators
- Gloria Reeves, MD, Principal investigator, University of MarylandLinmarie Sikich, MD, Principal investigator, University of North Carolina, Division of Child and Adolescent PsychiatryChristoph Correll, MD, Principal investigator, The Zucker Hillside HospitalMark A. Riddle, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00806234
- Sponsor's protocol ID
- R01MH080270
- Other IDs
- R01MH080270, DSIR 84-CTS
- Acronym
- IMPACT
- Status last verified
- Apr 2017
- First submitted
- 9 Dec 2008
- Last updated
- 25 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Reeves GM, Keeton C, Correll CU, Johnson JL, Hamer RM, Sikich L, Hazzard L, Alderman C, Scheer A, Mabe M, Kapoor S, Sheridan E, Borner I, Bussell K, Pirmohamed S, Bethea TC, Chekuri R, Gottfried R, Reinblatt SP, Santana E, Riddle MA. Improving metabolic parameters of antipsychotic child treatment (IMPACT) study: rationale, design, and methods. Child Adolesc Psychiatry Ment Health. 2013 Aug 15;7(1):31. doi: 10.1186/1753-2000-7-31.
PubMed 23947389
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Metabolic Parameters of Antipsychotic Child Treatment (IMPACT)
- ClinicalTrials.gov ID
- NCT00806234
- Acronym / sponsor ID
- IMPACT / R01MH080270
- Conditions
- Psychotic Disorders
- Keywords
- Weight Gain, Obesity, IMPACT, Antipsychotic Treatment, Excessive Weight Gain Associated With Antipsychotic Treatment, Hybrid Efficacy/Effectiveness Design, Reducing Weight Gain, Improving Metabolic Parameters
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), University of Maryland, University of North Carolina, Chapel Hill, The Zucker Hillside Hospital
- Study start
- Jan 2009
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 10 Dec 2008 (estimated)
- Results
- Posted 25 Apr 2017
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 test the effectiveness of two different treatments for children and adolescents who have gained weight on their antipsychotic medications.
Detailed description
Disorders that involve severe dysregulation of mood or thoughts in children -- such as early onset bipolar spectrum (BPS) and schizophrenia spectrum (SS) disorders -- are commonly treated with antipsychotic medications. However, many of the newest and most commonly prescribed antipsychotic medications can cause weight gain and metabolic dysfunctions. Use of these newer antipsychotics, called second generation antipsychotics (SGAs), is increasing rapidly in children, and the risk of weight gain from SGAs is higher among children than adults. Excessive weight gain can lead to obesity, which, in turn, can lead to increased health care costs, increased risk of sickness, and lower life expectancy. These factors are enhanced in children and adolescents who grow up obese.
Two different strategies to reduce weight gain and metabolic side effects from SGAs will be tested in this study. The first strategy involves switching from the current SGA to a lower risk agent (aripiprazole or perphenazine) hypothesized to result in weight loss and improved metabolic functioning. The second strategy involves taking the medication metformin in addition to the current SGA. Metformin is approved by the Food and Drug Administration (FDA) to promote weight loss in youth with diabetes and has been effective in reducing weight in youth taking SGAs.
Participation in this study will last between 26 and 27 weeks and will be divided into two parts. The first part will last 2 to 3 weeks and include three study visits. During this part, participants will undergo a physical exam, an electrocardiogram (EKG), a dual energy X-ray absorptiometry (DXA) test, and blood tests. The DXA measures body fat.
The second part will last 24 weeks and include nine study visits. During this part, participants will be randomly assigned to one of three conditions: gradual switch of current SGA medication to either aripiprazole or perphenazine, addition of metformin to current SGA medication, or no change to treatment with current SGA medication. Visits will take place on Weeks 1, 2, 4, 6, 8, 12, 16, 20, and 24. At each visit, participants will meet with a study doctor who will assess symptoms and side effects, and participants and their guardians will receive information and recommendations about childhood obesity and weight loss. There will also be monthly urine pregnancy tests, and two blood tests.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetineParticipants will continue on current antipsychotic medication. |
| 2 | Experimental | Drug: Aripiprazole or PerphenazineParticipants will undergo a staggered switch from current antipsychotic medication to aripiprazole or perphenazine. |
| 3 | Experimental | Drug: MetforminParticipants will add metformin to current antipsychotic medication treatment. |
Who may qualify
- Ages
- 8 to 19 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- DSM diagnoses that have an FDA indication for atypical antipsychotic use for at least one agent in the respective pediatric or adult age group. Specifically, primary DSM-IV diagnosis of Early Onset Schizophrenia Spectrum (EOSS; schizophrenia, schizoaffective disorder, schizophreniform disorder, psychotic disorder NOS); Bipolar Spectrum (bipolar I, II and NOS); Major depressive disorder with psychosis; Mood disorder NOS corresponding to Leibenluft and colleagues severely mood dysregulated (SMD) broad spectrum bipolar disorder; Mood disorder NOS corresponding to irritability associated with autism spectrum disorders; or - for adult teen participants aged 18-19 years - Major depressive disorder. Diagnoses will be determined by clinical interview, Leibenluft's modification of the K-SADS-PL, and the "Aberrant Behavior Checklist" (cutoff score of 18, as used by FDA for approval of risperidone and aripiprazole in minors).
- Clinically stable on current treatment regimen for at least 30 days, as assessed in a three-step process
- Current SGA treatment with olanzapine, quetiapine, risperidone, ziprasidone aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine for ≥ 8 weeks
- Stable dose of current SGA and psychotropic co-medications for at least 30 days
- Body mass index (BMI) at least in the 85th percentile for age and gender
Key exclusion criteria (16 listed)
- Treatment with any medication (other than the currently prescribed psychotropic medications) that would significantly alter glucose, insulin, or lipid levels. Exception: orlistat and amantadine are permitted if the individual has taken the drug for at least one year without weight loss.
- Major neurological or medical illness that affects weight gain or that would prevent participation in physical activities
- Fasting glucose levels indicating need for prompt treatment
- Pediatrician or pediatric gastroenterologist recommendation to address abnormal fasting labs by pursuing more active treatment than those in the 2007 American Medical Association guidelines
- Diagnosis of anorexia nervosa or bulimia nervosa, as based on current or lifetime DSM-IV criteria
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 |
|---|---|---|
| Aripiprazole or PerphenazineAlso: Abilify, TrilafonBaseline second generation antipsychotic (SGA) treatment will be gradually decreased and discontinued over 8 weeks while treatment with aripiprazole or perphenazine will be increased to effective levels. | Drug | 2 |
| MetforminAlso: GlucophageMetformin treatment will be added to current SGA treatment, with dosing based on participant weight and increased according to a preset titration schedule unless side effects interfere. | Drug | 3 |
| Olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetineAlso: Zyprexa, Seroquel, Risperdal, Geodon, Abilify, Saphris, Sycrest, Fanapt, Fanapta, Zomaril, Latuda, Invega, SymbyaxCurrent antipsychotic medication will be continued throughout the treatment period, with changes in dose only made as clinically indicated | Drug | 1 |
Primary outcome
Body Mass Index (BMI) Z-score Change
Time frame: Change from baseline to 24 weeks
3 secondary outcomes
Change in Whole Body Insulin Sensitivity Index
Time frame: Change from baseline to 24 weeks
Triglyceride Levels
Time frame: Change from baseline to 24 weeks
Change in Low Density Lipoprotein (LDL) Cholesterol Level
Time frame: From Baseline to Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23947389Reeves GM, Keeton C, Correll CU, Johnson JL, Hamer RM, Sikich L, Hazzard L, Alderman C, Scheer A, Mabe M, Kapoor S, Sheridan E, Borner I, Bussell K, Pirmohamed S, Bethea TC, Chekuri R, Gottfried R, Reinblatt SP, Santana E, Riddle MA. Improving metabolic parameters of antipsychotic child treatment (IMPACT) study: rationale, design, and methods. Child Adolesc Psychiatry Ment Health. 2013 Aug 15;7(1):31. doi: 10.1186/1753-2000-7-31.
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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.
Gloria Reeves, MD principal investigator
University of Maryland
Linmarie Sikich, MD principal investigator
University of North Carolina, Division of Child and Adolescent Psychiatry
Christoph Correll, MD principal investigator
The Zucker Hillside Hospital
4 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 Aripiprazole or Perphenazine, Metformin and Olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine in people with Psychotic Disorders, run by Johns Hopkins University at 4 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 9 inclusion and 16 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: finished, as of the sponsor's last update on 25 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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. 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?
Yes. Results are posted in the registry (first posted 25 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Body Mass Index (BMI) Z-score Change (time frame: Change from baseline to 24 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 NCT00806234, which also lists 1 linked publication.
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 25 Apr 2017.