Clozapine Induced Weight Gain

Study Overview
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Brief Summary
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Clozapine is prescribed to patients with psychosis in whom other treatments have not worked. Research has shown, however, that clozapine may be associated with weight gain and abnormal blood sugar levels in some patients. There is strong evidence to suggest that genetic variation between individuals plays an important role in the development of these side effects in response to the medication. Our research aims to evaluate the effects of two genes and the blood level of clozapine on side-effects such as weight changes and blood sugar levels in patients receiving clozapine treatment. From out-patient clinics in Cwm Taf UHB, the investigators aim to recruit 160 patients who are taking clozapine; collect information/ measurements from recruits relating to size/ weight/ BMI, risk of diabetes and blood samples to measure markers of blood sugar, fat/lipids, clozapine and its breakdown products, blood cells and variants of two specific genes. From this information the investigators will be particularly interested to understand if there is any association between the variation in these two genes with weight gain or changes in blood sugar, in patients taking clozapine.

Official Title
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Clozapine Induced Weight Gain: A Pharmacogenetic Study

Conditions
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Weight Gain, Antipsychotic Agents, Pharmacogenetics

Intervention / Treatment
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* Other: No study intervention - observational study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or over Taking/compliant with clozapine antipsychotic medications. Patients meeting the ICD-10 criteria for a diagnosis of schizophrenia, schizoaffective or borderline personality disorders. Exclusion Criteria: History of current alcohol/illicit substance dependency. Unable/ unsuitable to complete the study protocol e.g. acutely ill, suicidal or aggressive patients. Unable to consent to the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: No study intervention - observational study|This is an observational study where the comparative groups will be determined by the genetic variants (SNPs) of subjects and not an intervention, per se.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body-mass index (BMI) | BMI will be calculated by weight (kg)/ height^2 (m^2). | 12 months | 
| Leptin gene promoter region single nucleotide polymorphisms (SNPs) (rs7799039) | SNPs will be determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis to determine (c.-2548G or c.-2548A) . | 12 months | 
| Serotonin 5-HT 2C receptor gene single nucleotide polymorphisms (SNPs) (rs3813929) | SNPs will be determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis to determine (c.-759C or c.-759T) . | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood haemoglobin A1c concentration | Haemoglobin A1c concentrations will be determined by ion-exchange HPLC (G8, Tosoh, Amsterdam, Netherlands) | 6 months | 
| Waist:hip ratio | Waist:hip ratio will be calculated by waist circumference (cm)/hips circumference (cm) | 12 months | 
| Lipid profile | Serum lipid profiles will include total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride. These will be measured by enzymatic colorimetric methods on cobas-Roche analysers (Roche, Burges Hill, UK) except LDL cholesterol, which will be calculated using the Friedewald equation ([LDL cholesterol] = [Total cholesterol] - ([Triglyceride] / 2.2) - [HDL cholesterol] | 12 months | 
| Clozapine side effects assessment by Clinical Global Impression (CGI) scale | Clinical Global Impression (CGI) scale is a validated tool to assess clozapine side effects (Ref: Guy W, editor. ECDEU Assessment Manual for Psychopharmacology. 1976. Rockville,MD, U.S. Department of Health, Education, and Welfare) | 12 months | 
| Clozapine:nor clozapine ratio | Clozapine:nor clozapine ratio is calculated by clozapine (ug/L)/ nor clozapine (ug/L) both measured by high-performance liquid chromatography with diode-array detection. | 12 months |