ObesityNCT04815122
Correlation Between COMT Val158Met Polymorphism and Dopaminergic Transporter Density (DAT) in Obese Women
An observational study of Obesity, run by University of Sao Paulo at 1 site in Brazil.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 20 to 40 years, women only
- Conditions the study is for
- Obesity
- What is being tested?
- SPECT TRODAT-1
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 38 participants
- Where
- 1 siteBrazil
- Study dates
- Apr 2021to Nov 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 40 years
- Women only
- No healthy volunteers
- Adult
Study population: Young women with obesity (BMI 30-35kg/m2), with and without COMT Val158Met polymorphism who participated in a previous study registered at clinicaltrials.gov (NCT02953353).
Who may be able to join
- Women with obesity (BMI 30-35kg/m2), with and without COMT Val158Met polymorphism.
Who cannot join
- pregnancy
- any active psychiatric or neurological condition at the time of joining the study
- any other significant medical condition
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Clinical Hospital of Ribeirão Preto Medical School
Ribeirão Preto, São Paulo, 14048-900
About this study
Official title: Correlation Between the Presence of COMT Val158Met Polymorphism and Dopaminergic Transporter Density (DAT) in Obese Young Women
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.
Read the detailed description
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.
- Conditions
- Obesity
- Being tested
- SPECT TRODAT-1
- Keywords
- Obesity, Genetic polymorphism, Dopamine
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SPECT TRODAT-1Radiation
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.
| Study group | Role | What they receive |
|---|---|---|
| Carriers of the Met allele of the COMT Val158Met polymorphism | Women with obesity carriers of the Met allele of the COMT Val158Met polymorphism Receives: Radiation: SPECT TRODAT-1 | |
| Non-carriers of the Met allele of the COMT Val158Met polymorphism | Women with obesity non-carriers of the Met allele of the COMT Val158Met polymorphism Receives: Radiation: SPECT TRODAT-1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: During the procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2021
- Study startApr 2021 (estimated)
- Primary completionNov 2021 (estimated)
- Study completionNov 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by University of Sao PauloThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Responsible party
- Principal investigator, Vivian Marques Miguel Suen, University of Sao Paulo
- Investigators
- Vivian MM Suen, MD, PhD, Principal investigator, University of Sao PauloLauro Winchert-Ana, MD, PhD, Principal investigator, University of Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04815122
- Sponsor's protocol ID
- Process HCRP 3.844.428
- Status last verified
- Mar 2021
- First submitted
- 5 Mar 2021
- Last updated
- 24 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Avsar O, Kuskucu A, Sancak S, Genc E. Are dopaminergic genotypes risk factors for eating behavior and obesity in adults? Neurosci Lett. 2017 Jul 27;654:28-32. doi: 10.1016/j.neulet.2017.06.023. Epub 2017 Jun 16.
PubMed 28629779Barnett JH, Scoriels L, Munafo MR. Meta-analysis of the cognitive effects of the catechol-O-methyltransferase gene Val158/108Met polymorphism. Biol Psychiatry. 2008 Jul 15;64(2):137-44. doi: 10.1016/j.biopsych.2008.01.005. Epub 2008 Mar 14.
PubMed 18339359Chen PS, Yang YK, Yeh TL, Lee IH, Yao WJ, Chiu NT, Lu RB. Correlation between body mass index and striatal dopamine transporter availability in healthy volunteers--a SPECT study. Neuroimage. 2008 Mar 1;40(1):275-9. doi: 10.1016/j.neuroimage.2007.11.007. Epub 2007 Nov 21.
PubMed 18096411Fassini PG, Das SK, Suen VMM, Magerowski G, Marchini JS, da Silva Junior WA, Changyu S, Alonso-Alonso M. Appetite effects of prefrontal stimulation depend on COMT Val158Met polymorphism: A randomized clinical trial. Appetite. 2019 Sep 1;140:142-150. doi: 10.1016/j.appet.2019.05.015. Epub 2019 May 13.
PubMed 31095973Fassini PG, Das SK, Magerowski G, Marchini JS, da Silva Junior WA, da Silva IR, de Souza Ribeiro Salgueiro R, Machado CD, Suen VMM, Alonso-Alonso M. Noninvasive neuromodulation of the prefrontal cortex in young women with obesity: a randomized clinical trial. Int J Obes (Lond). 2020 Jun;44(6):1279-1290. doi: 10.1038/s41366-020-0545-3. Epub 2020 Feb 19.
PubMed 32076105Fonteneau C, Redoute J, Haesebaert F, Le Bars D, Costes N, Suaud-Chagny MF, Brunelin J. Frontal Transcranial Direct Current Stimulation Induces Dopamine Release in the Ventral Striatum in Human. Cereb Cortex. 2018 Jul 1;28(7):2636-2646. doi: 10.1093/cercor/bhy093.
PubMed 29688276Horstmann A, Fenske WK, Hankir MK. Argument for a non-linear relationship between severity of human obesity and dopaminergic tone. Obes Rev. 2015 Oct;16(10):821-30. doi: 10.1111/obr.12303. Epub 2015 Jun 22.
PubMed 26098597Van Laere K, De Ceuninck L, Dom R, Van den Eynden J, Vanbilloen H, Cleynhens J, Dupont P, Bormans G, Verbruggen A, Mortelmans L. Dopamine transporter SPECT using fast kinetic ligands: 123I-FP-beta-CIT versus 99mTc-TRODAT-1. Eur J Nucl Med Mol Imaging. 2004 Aug;31(8):1119-27. doi: 10.1007/s00259-004-1480-6. Epub 2004 Apr 3.
PubMed 15064872Slifstein M, Kolachana B, Simpson EH, Tabares P, Cheng B, Duvall M, Frankle WG, Weinberger DR, Laruelle M, Abi-Dargham A. COMT genotype predicts cortical-limbic D1 receptor availability measured with [11C]NNC112 and PET. Mol Psychiatry. 2008 Aug;13(8):821-7. doi: 10.1038/mp.2008.19. Epub 2008 Mar 4.
PubMed 18317466Volkow ND, Wang GJ, Telang F, Fowler JS, Thanos PK, Logan J, Alexoff D, Ding YS, Wong C, Ma Y, Pradhan K. Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors. Neuroimage. 2008 Oct 1;42(4):1537-43. doi: 10.1016/j.neuroimage.2008.06.002. Epub 2008 Jun 13.
PubMed 18598772Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W, Netusil N, Fowler JS. Brain dopamine and obesity. Lancet. 2001 Feb 3;357(9253):354-7. doi: 10.1016/s0140-6736(00)03643-6.
PubMed 11210998
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Correlation Between the Presence of COMT Val158Met Polymorphism and Dopaminergic Transporter Density (DAT) in Obese Young Women
- ClinicalTrials.gov ID
- NCT04815122
- Acronym / sponsor ID
- Process HCRP 3.844.428
- Conditions
- Obesity
- Keywords
- Obesity, Genetic polymorphism, Dopamine
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 38 participants (estimated)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Study start
- Apr 2021 (estimated)
- Primary completion
- Nov 2021 (estimated)
- Study completion
- Nov 2021 (estimated)
- First posted
- 24 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Carriers of the Met allele of the COMT Val158Met polymorphism | – | Radiation: SPECT TRODAT-1Women with obesity carriers of the Met allele of the COMT Val158Met polymorphism |
| Non-carriers of the Met allele of the COMT Val158Met polymorphism | – | Radiation: SPECT TRODAT-1Women with obesity non-carriers of the Met allele of the COMT Val158Met polymorphism |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Young women with obesity (BMI 30-35kg/m2), with and without COMT Val158Met polymorphism who participated in a previous study registered at clinicaltrials.gov (NCT02953353).
Key inclusion criteria (1 listed)
- Women with obesity (BMI 30-35kg/m2), with and without COMT Val158Met polymorphism.
Key exclusion criteria (3 listed)
- pregnancy
- any active psychiatric or neurological condition at the time of joining the study
- any other significant medical condition
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SPECT TRODAT-1The 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. | Radiation | Carriers of the Met allele of the COMT Val158Met polymorphism, Non-carriers of the Met allele of the COMT Val158Met polymorphism |
Primary outcome
Density of Dopaminergic transporters (DAT)
Time frame: During the procedure
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2021.
- Background: PubMed 28629779Avsar O, Kuskucu A, Sancak S, Genc E. Are dopaminergic genotypes risk factors for eating behavior and obesity in adults? Neurosci Lett. 2017 Jul 27;654:28-32. doi: 10.1016/j.neulet.2017.06.023. Epub 2017 Jun 16.
- Background: PubMed 18339359Barnett JH, Scoriels L, Munafo MR. Meta-analysis of the cognitive effects of the catechol-O-methyltransferase gene Val158/108Met polymorphism. Biol Psychiatry. 2008 Jul 15;64(2):137-44. doi: 10.1016/j.biopsych.2008.01.005. Epub 2008 Mar 14.
- Background: PubMed 18096411Chen PS, Yang YK, Yeh TL, Lee IH, Yao WJ, Chiu NT, Lu RB. Correlation between body mass index and striatal dopamine transporter availability in healthy volunteers--a SPECT study. Neuroimage. 2008 Mar 1;40(1):275-9. doi: 10.1016/j.neuroimage.2007.11.007. Epub 2007 Nov 21.
- Background: PubMed 31095973Fassini PG, Das SK, Suen VMM, Magerowski G, Marchini JS, da Silva Junior WA, Changyu S, Alonso-Alonso M. Appetite effects of prefrontal stimulation depend on COMT Val158Met polymorphism: A randomized clinical trial. Appetite. 2019 Sep 1;140:142-150. doi: 10.1016/j.appet.2019.05.015. Epub 2019 May 13.
- Background: PubMed 32076105Fassini PG, Das SK, Magerowski G, Marchini JS, da Silva Junior WA, da Silva IR, de Souza Ribeiro Salgueiro R, Machado CD, Suen VMM, Alonso-Alonso M. Noninvasive neuromodulation of the prefrontal cortex in young women with obesity: a randomized clinical trial. Int J Obes (Lond). 2020 Jun;44(6):1279-1290. doi: 10.1038/s41366-020-0545-3. Epub 2020 Feb 19.
- Background: PubMed 29688276Fonteneau C, Redoute J, Haesebaert F, Le Bars D, Costes N, Suaud-Chagny MF, Brunelin J. Frontal Transcranial Direct Current Stimulation Induces Dopamine Release in the Ventral Striatum in Human. Cereb Cortex. 2018 Jul 1;28(7):2636-2646. doi: 10.1093/cercor/bhy093.
- Background: PubMed 26098597Horstmann A, Fenske WK, Hankir MK. Argument for a non-linear relationship between severity of human obesity and dopaminergic tone. Obes Rev. 2015 Oct;16(10):821-30. doi: 10.1111/obr.12303. Epub 2015 Jun 22.
- Background: PubMed 15064872Van Laere K, De Ceuninck L, Dom R, Van den Eynden J, Vanbilloen H, Cleynhens J, Dupont P, Bormans G, Verbruggen A, Mortelmans L. Dopamine transporter SPECT using fast kinetic ligands: 123I-FP-beta-CIT versus 99mTc-TRODAT-1. Eur J Nucl Med Mol Imaging. 2004 Aug;31(8):1119-27. doi: 10.1007/s00259-004-1480-6. Epub 2004 Apr 3.
- Background: PubMed 18317466Slifstein M, Kolachana B, Simpson EH, Tabares P, Cheng B, Duvall M, Frankle WG, Weinberger DR, Laruelle M, Abi-Dargham A. COMT genotype predicts cortical-limbic D1 receptor availability measured with [11C]NNC112 and PET. Mol Psychiatry. 2008 Aug;13(8):821-7. doi: 10.1038/mp.2008.19. Epub 2008 Mar 4.
- Background: PubMed 18598772Volkow ND, Wang GJ, Telang F, Fowler JS, Thanos PK, Logan J, Alexoff D, Ding YS, Wong C, Ma Y, Pradhan K. Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors. Neuroimage. 2008 Oct 1;42(4):1537-43. doi: 10.1016/j.neuroimage.2008.06.002. Epub 2008 Jun 13.
- Background: PubMed 11210998Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W, Netusil N, Fowler JS. Brain dopamine and obesity. Lancet. 2001 Feb 3;357(9253):354-7. doi: 10.1016/s0140-6736(00)03643-6.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vivian MM Suen, MD, PhD principal investigator
University of Sao Paulo
Lauro Winchert-Ana, MD, PhD principal investigator
University of Sao Paulo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Obesity, run by University of Sao Paulo at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Priscila G Fassini, PhD (+55 16 36022366, priscilafassini@usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Density of Dopaminergic transporters (DAT) (time frame: During the procedure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04815122, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2021.