- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00894738
Biomarkers of Cardiometabolic Risk in Children Treated With Antipsychotics: A Preliminary Study of Direct Measures
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Carotid artery intima media wall thickness (IMT) is one of the most developed biomarkers of cardiometabolic risk, with established reliability and predictive validity, and has been utilized as a surrogate endpoint for cardiovascular disease progression in FDA-reviewed registration studies. This technique has also been used in children and adolescents without psychiatric disorders, indicating that changes in IMT are positively correlated with metabolic syndrome criteria. Magnetic Resonance Spectroscopy (1H MRS) to quantify hepatic triglyceride content (HTGC) is a promising new marker of cardiometabolic risk, especially given the importance of nocturnal circulating free fatty acids in the development of insulin resistance leading to type 2 diabetes. Fatty liver, related in part to obesity, is the most common liver abnormality found in children ages 2-19, with one in ten children manifesting signs of macrovascular steatohepatitis. 1H MRS is a well-established methodology used to measure HTGC that correlates well with liver biopsy results. This technique has been studied in obese children without psychiatric disorders, and is widely considered to be the optimal noninvasive means by which to measure HTGC. Unfortunately, neither of these promising methods have been applied to the study of cardiometabolic risk in children with psychiatric disorders.
It is important to now study these biomarkers in psychiatric populations, where individuals are subject to treatments that can increase risk. Our group is experienced in the application of sophisticated, gold standard techniques for measuring cardiometabolic risk in psychiatric populations, and is-to our knowledge-the only group in the US using sensitive methodologies like stable isotopomer euglycemic clamps to study the pathophysiology leading to diabetes and cardiovascular disease in the mentally ill. An important goal of studying these biomarkers is to ultimately determine which of the more commonly available conventional risk measures (e.g., lipid profiles, adiposity measures) can be used alone or in combination to accurately identify children at highest risk, to aid in the development and targeting of effective interventions.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
The inclusion criteria for the treatment group participants are: i) aged approximately 6-18 years; ii) BMI percentile between approximately 25 and 99; iii) otherwise healthy and meets DSM-IV criteria for one or more childhood onset psychiatric disorder, any type (determined by semi-structured Missouri Assessment of Genetics Interview for Children or MAGIC-described below and at the discretion of the PI), treated with an antipsychotic > approximately 12 weeks; iv) able to give assent and have a guardian that can provide informed consent; and v) no antipsychotic medication dose changes for approximately 1 month, and no other medication changes for 1 month prior to study enrollment.
The inclusion criteria for healthy controls are: i) aged 6-18 years; ii) BMI percentile between approximately 25 and 99 iii) otherwise healthy and at the PI's discretion do not meet DSM-IV criteria for any Axis I psychiatric illness; iv) not currently taking any medications; and v) able to give assent, and have a guardian that can provide informed consent.
The exclusion criteria are: i) active suicidality or a primary diagnosis of major depressive disorder; ii) any lifetime use of antipsychotics; individual subjects with a remote, brief prior antipsychotic exposure 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) subjects 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, as some 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 and SSRI's is permitted in order to maintain the generalizability of the sample); v) IQ < 70 (based on school records and/or evaluation by clinician); vi) current substance abuse; 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.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
antipsychotic treated
Children with psychiatric diagnoses who are currently treated with antipsychotic medications.
|
Magnetic Resonance Spectroscopy (MRS) of the liver to determine hepatic triglyceride content; ultrasound (US) of the carotid artery to determine intima-media thickness; dual energy X-ray absorptiometry (DEXA) to determine body composition; fasting lipids, fasting insulin, C-reactive protein, liver enzymes and fibrinogen levels.
|
healthy control
Age- and gender-matched children who do not have a psychiatric diagnosis, are not taking antipsychotic medications, and are otherwise healthy.
|
Magnetic Resonance Spectroscopy (MRS) of the liver to determine hepatic triglyceride content; ultrasound (US) of the carotid artery to determine intima-media thickness; dual energy X-ray absorptiometry (DEXA) to determine body composition; fasting lipids, fasting insulin, C-reactive protein, liver enzymes and fibrinogen levels.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Carotid Artery Intima-media Thickness Measured by Ultrasonography.
Time Frame: Week 1
|
Week 1
|
Intrahepatic Triglyceride Content (IHTG) Measure by Liver Magnetic Resonance Spectroscopy.
Time Frame: Week 1
|
Week 1
|
Collaborators and Investigators
Investigators
- Principal Investigator: Ginger E Nicol, MD, Washington University School of Medicine
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 56790
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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