Clinical trial NCT00752960: DNA Diagnostics for Minimizing Metabolic Side-Effects of Antipsychotics
Official title: DNA Diagnostics for Minimizing Metabolic Side-Effects of Antipsychotics
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Psychoses
Keywords: single nucleotide polymorphism, SNP, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, metabolic syndrome
Lead sponsor: Genomas, Inc
Sponsor class: INDUSTRY
Collaborators: name: Hartford Hospital
name: University of Kentucky
First posted: 2008-09-16
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients treated for psychoses

Brief summary: The purpose of this study is to assess patients treated with the antipsychotics aripiprazole (Abilify®), olanzapine (Zyprexa®), quetiapine (Seroquel®), risperidone (Risperdal®), or ziprasidone (Geodon®) and to identify genetic variations more commonly found in individuals who develop diabetic metabolic signs and symptoms, which include changes in blood lipids, blood glucose, blood pressure, and body weight.

Detailed description: As many as 30% of psychiatric patients experience weight gain, central deposition of fat, dyslipidemia, increased blood glucose and hypertension--diabetic metabolic symptoms--upon treatment with atypical antipsychotic medication. As a result, cardiovascular disease risk is significantly increased.

The long-term goal of this collaborative study is to identify, for each individual atypical antipsychotic (AAP) medication, the gene variations associated with elevated risk of diabetic metabolic symptoms (DiMS). If such genes are identified, in the future genetic testing may help mental health care professionals choose treatment while minimizing the risk of undesirable side effects of antipsychotics. We propose to develop a novel product termed "Physiotype" to deliver personalized information for each patient on the drug specific risks among aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone. The Physiotype consists of a multi-gene ensemble of single nucleotide polymorphisms (SNPs) that, interpreted with a biomathematical algorithm, may explain most of the inter-individual differences in DiMS among the 5 AAPs. If this study does identify related genes, genetic tests will be developed to provide patients and health care professionals with tools to identify those patients who are at risk of developing adverse metabolic side effects to antipsychotics.

Eligibility criteria: Inclusion Criteria:

* receiving atypical antipsychotic therapy (olanzapine, aripiprazole, quetiapine, risperidone, or ziprasidone) for 3 months
* who have taken \>50% of the prescribed dose for the last month.

Exclusion Criteria:

* none

Primary outcomes:
measure: diabetic metabolic symptoms (DiMS): body weight, body mass index, waist circumference, blood pressure, triglycerides, total, LDL, and HDL cholesterol, blood glucose
timeFrame: after treatment with antipsychotic medication(s) for => 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Hartford Hospital Institute of Living
state: Connecticut
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
affiliation: Genomas, Inc
name: Gualberto Ruano, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ruano G, Blair CL, Bower B, Windemuth A, Kocherla M, Aleman Y, Pearlson G, Goethe JW, Schwartz HI. Somatic complications of psychotropic medications in a patient with multiple CYP2 drug metabolism deficiencies. Conn Med. 2007 Apr;71(4):197-200.
citation: de Leon J, Susce MT, Johnson M, Hardin M, Pointer L, Ruano G, Windemuth A, Diaz FJ. A clinical study of the association of antipsychotics with hyperlipidemia. Schizophr Res. 2007 May;92(1-3):95-102. doi: 10.1016/j.schres.2007.01.015. Epub 2007 Mar 8.
citation: Ruano G, Goethe JW, Caley C, Woolley S, Holford TR, Kocherla M, Windemuth A, de Leon J. Physiogenomic comparison of weight profiles of olanzapine- and risperidone-treated patients. Mol Psychiatry. 2007 May;12(5):474-82. doi: 10.1038/sj.mp.4001944. Epub 2007 Jan 2.
citation: Windemuth A, de Leon J, Goethe JW, Schwartz HI, Woolley S, Susce M, Kocherla M, Bogaard K, Holford TR, Seip RL, Ruano G. Validation of candidate genes associated with cardiovascular risk factors in psychiatric patients. Prog Neuropsychopharmacol Biol Psychiatry. 2012 Mar 30;36(2):213-9. doi: 10.1016/j.pnpbp.2011.08.001. Epub 2011 Aug 6.