Correlation Between COMT Val158Met Polymorphism and Dopaminergic Transporter Density (DAT) in Obese Women

Study Overview
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Brief Summary
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The present study aims to evaluate the correlation between the presence of COMT Val158Met polymorphism and the density of dopaminergic transporters (DAT) in young obese women.

Detailed Description
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The prevalence of obesity remains increasingly alarming in Brazil and worldwide. The most widely recommended therapy for obesity is lifestyle modification, however, implementing these changes that can lead to weight loss is difficult and maintaining a long-term weight loss is even more challenging. Consequently, an academic effort is required to understand the pathophysiology and treat obesity for the establishment of new approaches to reducing food intake. Recent evidence in the field of obesity and brain-based integration indicates a potential for designing new therapeutic interventions. Noninvasive neuromodulation of brain activity has been shown to be a technique that can help reduce food cravings and food intake and, more recently, body weight, offering a new way to treat obesity. However, recent studies have shown that this biomedical intervention could have a paradoxical effect related to COMT Val158Met polymorphism, which impacts dopamine levels in the prefrontal cortex. The potential mechanisms underlying this effect are unclear and future studies are needed to promote this clarification. This study aims to verify the influence of the COMT Val158Met polymorphism on the density of dopaminergic transporters in the presynaptic membrane of dopaminergic neurons, exploring the 3 dopaminergic pathways: via nigroestrital, mesolimbic and mesocortical. This investigation will be carried out through the cerebral SPECT using the radiopharmaceutical 99mTecnécio-TRODAT-1 in young obese women with and without COMT Val158Met polymorphism. In baseline conditions, the investigators will compare the SPECT 99mTc-TRODAT-1 of obese women with and without the COMT Val158Met polymorphism with a database of non-obese volunteers. Our hypothesis is that the study will facilitate understanding of the variability of the individual response of carriers and non-carriers of the Met allele of the COMT Val158Met polymorphism, affecting dopamine levels in the brain and to design, in the future, for the treatment of obesity based on the individuals' genotypic differences.

Official Title
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Correlation Between the Presence of COMT Val158Met Polymorphism and Dopaminergic Transporter Density (DAT) in Obese Young Women

Conditions
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Obesity

Intervention / Treatment
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* Radiation: SPECT TRODAT-1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with obesity (BMI 30-35kg/m2), with and without COMT Val158Met polymorphism. Exclusion Criteria: pregnancy any active psychiatric or neurological condition at the time of joining the study any other significant medical condition

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Carriers of the Met allele of the COMT Val158Met polymorphism<br>Women with obesity carriers of the Met allele of the COMT Val158Met polymorphism | Radiation: SPECT TRODAT-1<br>* The Single-photon Emission Tomography (SPECT) TRODAT-1 will be performed after the voluntary rest in a dark and silent room for 30 minutes, to eliminate possible influences from external stimuli; the radiopharmaceutical [99mTC] -TRODAT-1 will be injected through the venous access previously established, 4 hours after the injection of the radiopharmaceutical, the acquisition of cerebral SPECT will be performed in the two groups of obese women, with and without COMT Val158Met polymorphism. The images will be acquired on Philips BrightView XCT equipment, equipped with a double detector.<br>|
| Non-carriers of the Met allele of the COMT Val158Met polymorphism<br>Women with obesity non-carriers of the Met allele of the COMT Val158Met polymorphism | Radiation: SPECT TRODAT-1<br>* The Single-photon Emission Tomography (SPECT) TRODAT-1 will be performed after the voluntary rest in a dark and silent room for 30 minutes, to eliminate possible influences from external stimuli; the radiopharmaceutical [99mTC] -TRODAT-1 will be injected through the venous access previously established, 4 hours after the injection of the radiopharmaceutical, the acquisition of cerebral SPECT will be performed in the two groups of obese women, with and without COMT Val158Met polymorphism. The images will be acquired on Philips BrightView XCT equipment, equipped with a double detector.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Density of Dopaminergic transporters (DAT) | The primary outcome is to compare the density of dopaminergic transporters (DAT) in the 3 dopaminergic pathways: via nigroestrital, mesolimbic and mesocortical in obese women with and without COMT Val158Met polymorphism. | During the procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Genetic polymorphism, Dopamine