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Measurement of Cardiometabolic Risk in Antipsychotic-Treated Children

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2012 by Washington University School of Medicine
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01222494
First received: October 5, 2010
Last updated: July 19, 2012
Last verified: July 2012
  Purpose

This K23 award application is relevant to multiple topic areas in the recent Institute of Medicine (IOM) research priority list, as well as the recent IOM report brief and White House "Let's Move" Campaign focused on childhood obesity. The US prevalence of childhood-onset obesity and type 2 diabetes, both predictors of cardiovascular risk, have increased to epidemic proportions in recent decades. Children with mental illness, especially those treated with antipsychotic medications, are at additional risk for obesity and related risk conditions. Despite known increases in obesity-related outcomes, including premature mortality, associated with childhood-onset versus adult-onset obesity, there remains an under-appreciation of these risks in children. A variety of noninvasive techniques to assess cardiometabolic risk have begun to be applied in children, including carotid intima media thickness (IMT) measured by ultrasound, and hepatic and cardiac triglyceride content measured by 1H Magnetic Resonance Spectroscopy (MRS). These measures allow for the early, noninvasive study of metabolic risk. Unfortunately, none of these promising methods have been applied to the high-risk population of children with psychiatric disorders, and cardiac triglyceride content has not been evaluated in children at all, preventing accurate characterization of risk or the effectiveness of interventions the reduce risk in this vulnerable population. The overall aim of this two-study research plan is to characterize the level of measurable risk using these sensitive markers in treated and untreated children with mental health disorders, and to evaluate the magnitude of change in risk that can be observed using these biomarkers in children receiving a well established behavioral weight-loss intervention.


Condition Intervention
Pediatric Mental Disorders
Obesity
Metabolic Syndrome
Behavioral: Behavioral Weight Loss
Behavioral: Diet and Exercise Education

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Measurement of Cardiometabolic Risk in Antipsychotic-Treated Children

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Hepatic Triglyceride Content (HTGC) [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    1H Magnetic Resonance Spectroscopy (MRS) of liver will be used to assess intracellular triglyceride content at baseline and following 16 weeks of participation in an intensive behavioral weight loss intervention.

  • Carotid Artery Intima Media Thickness (IMT) [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    9-13-MHZ B-mode Carotid Ultrasound will be used to assess intima media thickness at baseline and following 16 weeks of participation in an intensive behavioral weight loss intervention.

  • Body Weight [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    To evaluate the effectiveness of a 16-week behavioral weight loss program focused on children with mental illness who are taking psychotropic medications.

  • Cardiac Triglyceride Content (CTGC) [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    1H Magnetic Resonance Spectroscopy (MRS) of hert will be used to assess intracellular triglyceride content at baseline and following 16 weeks of participation in an intensive behavioral weight loss intervention.

  • DEXA-measured adiposity [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    To evaluate the effect of participation in a 16-week behavioral weight loss program on adiposity.


Secondary Outcome Measures:
  • Fasting blood tests [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    To evaluate the effect of participation in a 16-week behavioral weight loss program has on fasting laboratory measures of cardiometabolic risk, including fasting lipids, insulin, glucose and adiponectin.

  • Non-fasting blood tests [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    To evaluate the effect of participation in a 16-week behavioral weight loss program on non-fasting measures of cardiometabolic risk, including fibrinogen and high sensitivity C-reactive protein.


Estimated Enrollment: 126
Study Start Date: July 2011
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Diet and Exercise Education
Patients randomized to this arm will receive diet and exercise education at regular intervals with a study clinician or coordinator.
Behavioral: Diet and Exercise Education
Participants assigned to this arm will receive medically validated, individualized diet and exercise education by a trained research professional.
Experimental: Behavioral Weight Loss
Patients randomized to this arm will engage in a manualized behavioral weight loss intervention that includes regular meetings with a trained study therapist.
Behavioral: Behavioral Weight Loss
The TODAY Lifestyle Program (TLP) is a family-based, behavioral weight loss program that has been employed in studies with overweight and obese children, as well as with children who have diabetes. For the proposed study, TLP will be modified to fit the needs of disruptive and behaviorally disturbed youth and their families. The modified program includes 16 weeks of intensive weekly intervention with a 6-month maintenance phase with monthly in-person visits and supplemental phone contacts as needed. Phone contacts will only replace in-person visits if absolutely necessary to achieve the visit.

Detailed Description:

The proposed research seeks to increase knowledge regarding biomarkers of metabolic risk in children with mental health conditions. This project will utilize sensitive, early biomarkers of disease risk, including hepatic triglyceride content (HTGC), as well as cardiac triglyceride content (CTGC) and carotid IMT, directly relevant to diabetes and cardiovascular disease risk, respectively. The overall aim of this two-study research plan is to characterize risk using these sensitive biomarkers in children with mental health disorders, and evaluate the magnitude of change observed in these biomarkers in children receiving an established behavioral weight-loss intervention. This will be accomplished using two studies:

Study 1) A case control cross sectional comparison of CTGC, HTCG and IMT values in three groups of overweight/obese children who are age-, gender- and BMI%ile-matched: antipsychotic-treated mentally ill children; mentally ill children not treated with antipsychotics; and untreated children with no mental illness (a reference group of lean healthy participants is also included)

Study 2) A randomized, controlled test of the effects of a 16-week behavioral weight loss intervention (vs. diet/exercise education) on CTGC, HTGC and IMT in overweight/obese antipsychotic-treated children (a reference group of non-mentally-ill children will receive active intervention only).

  Eligibility

Ages Eligible for Study:   6 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

INCLUSION CRITERIA FOR STUDIES 1 and 2:

  • 6-18 years old (at any point during study participation)
  • BMI percentile > 85 (EXCEPT for the Lean Healthy Reference Group in Study 1 which requires BMI percentile between 5-50)
  • Meet DSM-IV criteria for one or more childhood onset psychiatric disorders including disruptive behavior disorders (attention deficit disorder, conduct disorder, oppositional defiant disorder and disruptive behavior disorder not otherwise specified), affective disorders (bipolar affective disorder, major depressive disorder and mood disorder not otherwise specified), anxiety disorders (generalized anxiety disorder, obsessive compulsive disorder, separation anxiety, social and other specific phobias) as well as other disorders, including autism spectrum disorders (autistic disorder, Asperger's Syndrome and pervasive developmental disorder not otherwise specified), psychotic disorders (schizophreniform disorder, schizophrenia and psychotic disorder not otherwise specified) and movement disorders (tic disorder, Tourette's Syndrome) as determined by semi-structured semi-structured diagnostic interview and/or clinical evaluation, and/or psychiatric symptom assessments and/or ABC, described below in Sources and Materials, as deemed appropriate by the PI (EXCEPT for the Obese or Overweight Control Group and the Lean Healthy Reference Group in Study 1 and the Healthy Obese or Overweight Reference Groups in Study 2, none of which can meet criteria for any DSM-IV Axis I psychiatric illness)
  • Score of > 18 on the irritability subscale of the Aberrant Behavior Checklist score of > 8 on the modified Outburst Monitoring Scale prior to initiating antipsychotic treatment; the modified Outburst Monitoring Scale will be administered to parents and one or more collateral source (such as a teacher, social worker or alternate caregiver) by study staff to retrospectively gather information about symptoms of irritability and aggression prior to initiation of antipsychotic treatment);prior to initiating psychotropic medication EXCEPT for the Lean Healthy Reference Group in Study 1 and the Healthy Obese or Overweight Reference Groups in Study 2; the ABC questionnaire will be administered to parents and one or more collateral source (such as a teacher, social worker or alternate caregiver) by study staff to retrospectively gather information about symptoms of irritability and aggression prior to initiation of antipsychotic treatment)
  • Participants treated with any psychotropic medication may not have any medication changes for 1 month prior to study enrollment at the discretion of the PI, and Antipsychotic-Treated Participants must be treated with an antipsychotic > approximately 12 weeks with no antipsychotic medication dose changes for 1 month
  • The Healthy Overweight or Obese Control Group and Lean Healthy Reference Group of Study 1, and the Overweight or Obese Healthy Reference Group of Study 2 may not be currently taking any prescription medications (multivitamins, over the counter medications, glucocorticoid nasal spray and inhalers are permitted, as well as non-sedating antihistamines such as but not limited to Claritin (loratadine) and Zyrtec (cetirizine))
  • Participants between 6-17 years old will be able to give assent and have a parent/guardian that can provide written informed consent, and 18 year-old participants will be able to provide written informed consent.

EXCLUSION CRITERIA FOR STUDIES 1 and 2: i) Do not meet DSM-IV criteria for any Axis I psychiatric illness per PI discretion (EXCEPT for Lean Healthy reference group in Study 1 and Overweight or Obese Healthy reference group in Study 2); ii) Any lifetime use of antipsychotics (EXCEPT Antipsychotic-Treated Participants in Studies 1 and 2 and Non-Antipsychotic Treated Participants in Study 1, with the individuals in the latter group possibly having a remote, brief prior antipsychotic exposure that may be considered for enrollment on a case by case basis by the PI); iii) The presence of any serious medical disorder that may confound the assessment of relevant biologic measures or diagnoses, including: significant organ system dysfunction; endocrine disease, including type 1 or type 2 diabetes mellitus; coagulopathy; anemia; or acute infection; all based on PI discretion; iv) Participants regularly taking within the last 3 months any glucose lowering agent, lipid lowering agent, exogenous testosterone, recombinant human growth hormone, or any other endocrine agent that might confound substrate metabolism, oral glucocorticoids (glucocorticoid nasal spray and inhalers are permitted), sedating antihistamines (non-sedating antihistamines such as but not limited to Claritin (loratadine) and Zyrtec (cetirizine) are permitted), and certain mood stabilizing agents including antiepileptic medications (lamotrigine is permitted) and Lithium, as these medications may themselves worsen or otherwise alter weight gain, glucose and lipid regulation or otherwise make it difficult to assess the effects of the antipsychotic alone; (note that exposure to many psychotropic agents including stimulants, SSRI's and SNRI's are permitted in the Antipsychotic-Treated and Non-Antipsychotic Treated Groups in Study 1 in order to maintain the generalizability of the sample); v) IQ < 70 (based on school records and/or evaluation by clinician and at the discretion of the PI); vi) Current DSM IV diagnosed substance abuse or dependence; vii) Past history of, or current dyskinesia; viii) Stimulant dosage significantly higher (per PI judgment) than the equivalent of approximately 2 mg/kg/day methylphenidate equivalent dose (EXCEPT in the Obese or Overweight Control Group and the Lean Healthy Reference Group in Study 1 and the Healthy Obese or Overweight Reference Groups in Study 2, none of whom can be taking stimulant medications); and ix) Unable to provide assent or informed consent; x) Active suicidality or a primary diagnosis of depression.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01222494

Contacts
Contact: Julie A Schweiger, CCRC (314) 362-3153 schweigj@psychiatry.wustl.edu
Contact: Martha J Hessler (314) 362-2423 hesslerma@psychiatry.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Martha J Hessler, BS    314-362-2423    hesslerma@psychiatry.wustl.edu   
Contact: Julia A Schweiger    314-362-3153    schweigj@psychiatry.wustl.edu   
Principal Investigator: Ginger E Nicol, MD         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Ginger E Nicol, MD Washington University School of Medicine
  More Information

No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01222494     History of Changes
Other Study ID Numbers: 10-0425
Study First Received: October 5, 2010
Last Updated: July 19, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
Child Psychiatry
Obesity
Antipsychotic

Additional relevant MeSH terms:
Mental Disorders
Psychotic Disorders
Obesity
Metabolic Syndrome X
Schizophrenia and Disorders with Psychotic Features
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on August 28, 2014