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

NCT00806234 | Completed Phase 4 Results DMC

• 2 other identifiers: R01MH080270DSIR 84-CTS
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 4

Brief Summary

This study will test the effectiveness of two different treatments for children and adolescents who have gained weight on their antipsychotic medications.

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; Aripiprazole; Metformin; Risperdal; Seroquel; Quetiapine; Olanzapine; Zyprexa; Geodon; Risperidone; Abilify; Trilafon; Perphenazine; Glucophage; Paliperidone; Olanzapine/fluoxetine

Outcome Measures

Primary Outcomes (1)

• Body Mass Index (BMI) Z-score Change

  Change from baseline to 24 weeks

Secondary Outcomes (3)

• Change in Whole Body Insulin Sensitivity Index

  Change from baseline to 24 weeks

• Triglyceride Levels

  Change from baseline to 24 weeks

• Change in Low Density Lipoprotein (LDL) Cholesterol Level

  From Baseline to Week 24

Study Arms (3)

1

ACTIVE COMPARATOR

Participants will continue on current antipsychotic medication.

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.

Drug: Aripiprazole or Perphenazine

3

EXPERIMENTAL

Participants will add metformin to current antipsychotic medication treatment.

Drug: Metformin

Interventions

Aripiprazole or Perphenazine DRUG

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.

Also known as: Abilify, Trilafon

2

Metformin DRUG

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.

Also known as: Glucophage

3

Olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine DRUG

Current antipsychotic medication will be continued throughout the treatment period, with changes in dose only made as clinically indicated

Also known as: Zyprexa, Seroquel, Risperdal, Geodon, Abilify, Saphris, Sycrest, Fanapt, Fanapta, Zomaril, Latuda, Invega, Symbyax

1

Eligibility Criteria

• Age: 8 Years - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute of Mental Health (NIMH): collaborator
• University of Maryland: collaborator
• University of North Carolina, Chapel Hill: collaborator
• The Zucker Hillside Hospital: collaborator

Study Sites (4)

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

The Zucker Hillside Hospital

Glen Oaks, New York, 11004, United States

Location

University of North Carolina, Division of Child and Adolescent Psychiatry

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• 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.

  PMID: 23947389 BACKGROUND

MeSH Terms

Conditions

Psychotic Disorders; Weight Gain; Obesity; Tooth, Impacted

Interventions

Aripiprazole; Perphenazine; Metformin; Olanzapine; Quetiapine Fumarate; Risperidone; ziprasidone; asenapine; iloperidone; Lurasidone Hydrochloride; Paliperidone Palmitate; Fluoxetine; olanzapine-fluoxetine combination

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Tooth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Biguanides; Guanidines; Amidines; Benzodiazepines; Benzazepines; Dibenzothiazepines; Thiazepines; Thiepins; Pyrimidinones; Pyrimidines; Thiazoles; Azoles; Isoindoles; Isoxazoles; Propylamines; Amines

Limitations and Caveats

27 subjects were randomized between 10/2009-10/2013 into three groups (CONTROL=47; MET=49; SWITCH=31). Safety analyses excluded 4 participants (CONTROL=1, MET=2, SWITCH=1) who discontinued at baseline.

Results Point of Contact

• Title: Dr. Mark Riddle
• Organization: Johns Hopkins University

mriddle1@jhmi.edu

410-302-6120

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 9, 2008
• First Posted: December 10, 2008
• Study Start: January 1, 2009
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: April 25, 2017
• Results First Posted: April 25, 2017

Record last verified: 2017-04

Locations

US (4)