Reducing Weight Gain and Improving Metabolic Function in Children Being Treated With Antipsychotics (IMPACT)

Tracking Information
First Submitted Date ICMJE	December 9, 2008
First Posted Date ICMJE	December 10, 2008
Results First Submitted Date	July 2, 2016
Results First Posted Date	April 25, 2017
Last Update Posted Date	April 25, 2017
Study Start Date ICMJE	January 2009
Actual Primary Completion Date	March 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: April 21, 2017)	Body Mass Index (BMI) Z-score Change [ Time Frame: Change from baseline to 24 weeks ]
Original Primary Outcome Measures ICMJE; (submitted: December 9, 2008)	Body Mass Index (BMI) Z-score Change [ Time Frame: Measured at Week 24 ]
Change History	Complete list of historical versions of study NCT00806234 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: April 21, 2017)	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 ]
Original Secondary Outcome Measures ICMJE; (submitted: December 9, 2008)	Body fat mass [ Time Frame: Measured at Week 24 ]; Whole body insulin sensitivity index [ Time Frame: Measured at Week 24 ]; Triglyceride Levels [ Time Frame: Measured at Week 24 ]; Low density lipoprotein (LDL)-cholesterol level [ Time Frame: Measured at Week 24 ]; Metabolic syndrome [ Time Frame: Measured at Week 24 ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Reducing Weight Gain and Improving Metabolic Function in Children Being Treated With Antipsychotics
Official Title ICMJE	Improving Metabolic Parameters of Antipsychotic Child Treatment (IMPACT)
Brief Summary	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 Type ICMJE	Interventional
Study Phase	Phase 4
Study Design ICMJE	Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Psychotic Disorders
Intervention ICMJE	Drug: Aripiprazole or Perphenazine 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. Other Name: Abilify, Trilafon; Drug: Metformin 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. Other Name: Glucophage; Drug: Olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine Current antipsychotic medication will be continued throughout the treatment period, with changes in dose only made as clinically indicated Other Name: Zyprexa, Seroquel, Risperdal, Geodon, Abilify, Saphris, Sycrest, Fanapt, Fanapta, Zomaril, Latuda, Invega, Symbyax
Study Arms	Active Comparator: 1 Participants will continue on current antipsychotic medication. Intervention: Drug: Olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine; Experimental: 2 Participants will undergo a staggered switch from current antipsychotic medication to aripiprazole or perphenazine. Intervention: Drug: Aripiprazole or Perphenazine; Experimental: 3 Participants will add metformin to current antipsychotic medication treatment. Intervention: Drug: Metformin
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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: May 15, 2014)	127
Original Estimated Enrollment ICMJE; (submitted: December 9, 2008)	240
Actual Study Completion Date	March 2014
Actual Primary Completion Date	March 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: 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.; 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 Exclusion Criteria: 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; 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
Sex/Gender	Sexes Eligible for Study: All
Ages	8 Years to 19 Years (Child, Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00806234
Other Study ID Numbers ICMJE	R01MH080270( U.S. NIH Grant/Contract ); R01MH080270 ( U.S. NIH Grant/Contract ); DSIR 84-CTS
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Mark Riddle, MD, Johns Hopkins University
Study Sponsor ICMJE	Johns Hopkins University
Collaborators ICMJE	National Institute of Mental Health (NIMH); University of Maryland; University of North Carolina, Chapel Hill; The Zucker Hillside Hospital
Investigators ICMJE	Principal Investigator: Gloria Reeves, MD University of Maryland Principal Investigator: Linmarie Sikich, MD University of North Carolina, Division of Child and Adolescent Psychiatry Principal Investigator: Christoph Correll, MD The Zucker Hillside Hospital Principal Investigator: Mark A. Riddle, MD Johns Hopkins University
PRS Account	Johns Hopkins University
Verification Date	April 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP