| Conditions: |
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Pediatric Mental Disorders - Obesity - Metabolic Syndrome |
| Purpose: |
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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.
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| Study Summary: |
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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).
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| Criteria: |
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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.
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| NCT ID: |
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NCT01222494 |
| Primary Contact: |
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Principal Investigator
Ginger E Nicol, MD
Washington University School of Medicine
Julie A Schweiger, CCRC
Phone: (314) 362-3153
Email: schweigj@psychiatry.wustl.edu
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| Backup Contact: |
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Email: hesslerma@psychiatry.wustl.edu
Martha J Hessler
Phone: (314) 362-2423
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| Location Contact: |
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St. Louis, Missouri 63110
United States
Martha J Hessler, BS
Phone: 314-362-2423
Email: hesslerma@psychiatry.wustl.edu
Site Status: Recruiting |