Healthy Bodies, Healthy Kids

Obesity Clinical Trial

Official title:

Measurement of Cardiometabolic Risk in Antipsychotic-Treated Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01222494
• Other study ID #: 10-0425
• Secondary ID: K23MH092435
• Status: Completed
• Phase: N/A
• Start date: July 2011
• Est. completion date: March 2017

Study information

• Verified date: October 2018
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 (adiposity) and related risk conditions. A variety of noninvasive techniques to assess cardiometabolic risk have begun to be applied in children, including body composition measured with dual energy x-ray absorptiometry (DEXA), carotid intima media thickness (CIMT) measured by ultrasound, and hepatic triglyceride content measured using magnetic resonance (MR) imaging-estimated proton density fat fraction (PDFF). These measures allow for the early, noninvasive study of adiposity-related metabolic risk. 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.

Description:

This project will utilize sensitive, early biomarkers of disease risk, including whole body adiposity with DEXA, PDDF and CIMT, directly relevant to diabetes and cardiovascular disease risk. The primary goals of this study are to deliver an evidence-based weight loss intervention to the population of youth who are overweight or obese as a result of antipsychotic treatment, to characterize metabolic risk associated with weight using sensitive biomarkers, and to evaluate the magnitude of change observed in these biomarkers in children receiving an established behavioral weight-loss intervention.

Aim 1: To evaluate the main effect of time of 16 weeks of a Behavioral Weight Loss (BWL) intervention on DEXA-measured whole body adiposity in overweight/obese antipsychotic (AP)-treated children compared to nonpsychiatric (NP) overweight or obese healthy controls, and in AP-treated youth randomized to monthly Usual Care (UC).

Aim 2: To evaluate the main effect of time of 16 weeks of a BWL intervention on PDFF in overweight/obese AP-treated children compared to NP overweight or obese healthy controls, and in AP-treated youth randomized monthly UC.

Aim 3: To evaluate the main effect of time of 16 weeks of a weekly behavioral weight loss intervention on CIMT in overweight/obese AP-treated children compared to NP overweight or obese healthy controls, and in AP-treated youth randomized monthly UC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: March 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 18 Years

Eligibility

INCLUSION CRITERIA

• 6-18 years old (at any point during study participation)

• BMI percentile > 85

• 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 diagnostic interview (EXCEPT for the Obese or Overweight Control Group, none of whom can meet criteria for any DSM-IV Axis I psychiatric illness)

• Currently treated with an atypical antipsychotic medication (EXCEPT for the Obese or Overweight Healthy Control Group, none of whom can be treated with any psychotropic medications 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 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

• Do not meet DSM-IV criteria for any Axis I psychiatric illness per PI discretion (EXCEPT for Overweight or Obese Healthy reference group)

• Any lifetime use of antipsychotics (EXCEPT for Antipsychotic-Treated Participants, 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)

• 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 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)

• IQ < 70 (based on school records and/or evaluation by clinician and at the discretion of the PI)

• Current DSM IV diagnosed substance abuse or dependence

• Past history of, or current dyskinesia

• 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, none of whom can be taking stimulant medications)

• Unable to provide assent or informed consent

• Active suicidality or a primary diagnosis of depression

• Unwilling to allow study staff to contact subject's primary care physician to alert to any significant, abnormal clinical findings or test results obtained as part of study participation

Related Conditions & MeSH terms

• Child Mental Disorders
• Mental Disorders
• Metabolic Syndrome
• Metabolic Syndrome X
• Neurodevelopmental Disorders
• Obesity
• Psychotic Disorders

Intervention

Behavioral:
• Behavioral Weight Loss
This intervention 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, the program has been modified to fit the needs of disruptive and behaviorally disturbed youth and their families. The modified program includes 16 weeks of weekly visits with a study interventionist, and supplemental phone contacts as needed. Phone contacts will only replace in-person visits if absolutely necessary to achieve the visit.
• Diet and Exercise Education
Participants assigned to this arm will receive monthly medically validated, individualized diet and exercise education by a trained research professional.

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Aberrant Behavior Checklist (ABC)	Change From Baseline in Aberrant Behavior Checklist - Irritability Subscale at 16 Weeks	Baseline and 16 weeks
Primary	DEXA-measured Adiposity	Dual-Energy X-Ray Absorptiometry (DEXA) will be used to assess body fat at baseline and following 16 weeks of participation in a behavioral weight loss intervention.	Baseline and 16 weeks
Primary	Proton Density Fat Fraction (PDFF)	1H Magnetic Resonance Spectroscopy (MRS) of liver will be used to assess intracellular triglyceride content at baseline and following 16 weeks of participation in a behavioral weight loss intervention.	Baseline and 16 weeks
Primary	Carotid Artery Intima Media Thickness (CIMT)	9-13-MHZ B-mode Carotid Ultrasound will be used to assess intima media thickness at baseline and following 16 weeks of participation in a behavioral weight loss intervention.	Baseline and 16 weeks