ObesityNEWTONNCT03903757
Network Medicine, Epigenetics and Obesity
An observational study of Obesity and Type2 Diabetes, run by University of Campania Luigi Vanvitelli.
Trial summary
The prevalence of obesity is increasing and affects more than 650 million people of all ages to become one of the foremost global health threats. Obesity is a complex syndrome that can seriously impair health through a broad range of complications such as cardiovascular disease, type 1 and 2 diabetes (T1D and T2D)… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Obesity, Type2 Diabetes
- What is being tested?
- DNA methylome and total RNA sequencing
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- Dec 2019to Jun 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Study population: Subcutaneous adipose tissues located in the surgical incision will be withdrawn without the use of surgical devices in order to avoid the degradation of the biological sample from 50 obese subjects (25 obese subjects with Type 2 Diabetes vs 25 obese subjects without Type 2 Diabetes) undergoing bariatric surgery. As controls (n=50) we will recruit subcutaneous adipose tissues from patients without a clinical history of cardiovascular or dysmetabolic diseases undergoing to surgery for stress inguinal hernia.
Who may be able to join
- Meets the current American Diabetes Association guideline for diagnosis of diabetes (Diabetic group) and obesity
- Must be willing and able to comply with study requirements
- Must indicate their understanding of the study and willingness to participate by signing an appropriate informed consent form
Who cannot join
- History of cancer
- Malignancy disorders
- Active infections
- Chronic or immune-mediated diseases
- Primary disease requiring surgical intervention
- Unable to comply with the complication screening
Show all 10Show fewer
- Less than 18 y of age
- Pregnant or are planning to become pregnant during the duration of the investigation
- Life expectancy <12 m
- Currently participating in any other clinical investigation
About this study
Official title: Network-based Epigenome-Wide associaTion Study in Obesity precisioN Medicine: NEWTON Clinical Trial
The prevalence of obesity is increasing and affects more than 650 million people of all ages to become one of the foremost global health threats. Obesity is a complex syndrome that can seriously impair health through a broad range of complications such as cardiovascular disease, type 1 and 2 diabetes (T1D and T2D), cancer, musculoskeletal disorders, psychosocial imbalances, and reduced quality of life, and impacts the treatment of other conditions. Weight reduction has been shown to have a positive effect on these co-morbidities and may increase the effectiveness of treatments specific for other co-morbidities. Lifestyle modification is an integral part of the weight management journey, but is often insufficient on its own, and can be complimented by pharmacological and surgical add-on treatments to achieve greater and more sustainable weight loss, as appropriate. It is likely that there are subgroups of patients that are more suited to certain types of treatment and results risk dilution of perceived efficacy unless these groups are identified and treatment is personalised. The aim of this project is to identify pathophysiologically and clinically meaningful subgroups of obesity by performing Next Generation Sequencing (NGS) approaches and network based algorithm that will allow the optimisation of prevention and treatment of obesity and its complications.
Read the detailed description
Population study will be recruited at the Clinical Department of Internal Medicine and Specialistics, Department of Advanced Clinical and Surgical Sciences belonging to University of Campania "Luigi Vanvitelli". This study will be performed according to the principles outlined in the Helsinki Declaration. Subcutaneous adipose tissues located in the surgical incision will be withdrawn without the use of surgical devices in order to avoid the degradation of the biological sample from 50 obese subjects (25 obese subjects with Type 2 Diabetes vs 25 obese subjects without Type 2 Diabetes) undergoing bariatric surgery. As controls (n=50) we will recruit subcutaneous adipose tissues from patients without a clinical history of cardiovascular or dysmetabolic diseases undergoing to surgery for stress inguinal hernia. Clinical and demographic characteristics of the study population will be available from datasets generated by physicians.
From tissue samples the genomic DNA and the total RNA will be extracted. Genomic DNA will be extracted by using DNeasy Blood \& Tissue kit (QIAGEN), according to manufacturer protocol. Pooled DNA samples consisting of equal quantities of DNA (2 µg) from cases and controls will be shipped to Genomix4Life Genomics and Bioinformatics Service, to perform a global DNA methylation analysis. For this aim, it will be used the Human Methylation 27K BeadChip platform by using Bisulfite conversion technology (BBRS-Seq). Total RNA will be extracted from tissues using RNeasy Mini Kit (QIAGEN) according to manufacturer protocol. The cDNA library preparation will be performed starting from 4 ug of total RNA by using Illumina TruSeq Libraries and then sequenced at high coverage on the Illumina HiSeq 2500 NGS platform. Nucleic acid concentrations and quality control from Genomix4Life will be assessed by using Nanodrop spectrophotometer (Thermo Fisher Scientific) and Qubit assay (Thermo Fisher Scientific) and TapeStation 4200 (Agilent). The weighted human DNA methylation PPI network (WMPN) will be construct to obtain a obesity interactome in both subgroups (obese and obese with T2D vs controls) based on differentially methylated genes in order to identify putative useful diagnostic biomarkers. The TargetScan algorithm , by searching the conserved seed pairing regions in the 3' untraslated regions (UTR) of genes based on whole genome alignment, will be used to robustly predict miRNA-target gene pairs from the same study population.
- Conditions
- Obesity, Type2 Diabetes
- Being tested
- DNA methylome and total RNA sequencing
- Keywords
- Epigenetics, Network medicine, Personalized therapy
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DNA methylome and total RNA sequencingOther
Epigenomics tools combined with bioinformatic analysis to correlate putative useful clinical biomarkers with clinical features
| Study group | Role | What they receive |
|---|---|---|
| Obese subjects with and without T2D | Not described Receives: Other: DNA methylome and total RNA sequencing | |
| control subjects | Not described Receives: Other: DNA methylome and total RNA sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
DNA methylation pattern in adipose tissues
Using Methylation 27K BeadChip platform based on Bisulfite conversion technology, DNA methylation profile in adipose tissues of 25 preselected obese subject and 25 obese subjects respect with controls (n=50) will be performed.
Measured: 3 months
Bioinformatics analysis to predict putative novel candidate genes underlying obesity phenotype
The network-based algorithm "Weighted Human DNA methylation PPI network (WMPN)" will be applied to methylome data in order to obtain a disease module containing the crucial differentially methylated genes both in obese patients and obese patients with T2D compared to controls.
Measured: 6 months
RNA sequencing analysisin adipose tissues
RNA sequencing analysis by using Illumina HiSeq2000 Next Generatin Sequencing (NGS) platform will be performed for identifying differentially expressed micro-RNA and mRNA target both in obese patients and obese patients with T2D compared to controls.
Measured: 3 months
Secondary outcomes (4)
ROC curves analysis to evaluate putative DNA methylation/microRNA interactions
ROC curves analysis to evaluate putative DNA methylation/microRNA interactions as diagnostic biomarkers to discriminate obesity subgroups.
Measured: 12 months
Linear regression analysis and BMI (Kg/m2).
Linear regression to correlate epigenetic biomarkers with BMI (Kg/m2) in different soubgroups.
Measured: 12 months
Linear regression to correlate epigenetic biomarkers with proinflammatory cytokines
Linear regression to correlate epigenetic biomarkers with proinflammatory cytokines (TNF-α,IL-6, PCR) levels in different soubgroups.
Measured: 12 months
Linear regression to correlate epigenetic biomarkers with HOMA index
Linear regression to correlate epigenetic biomarkers with clinical variables, such as HOMA index glycemia(mmol/L) x insulinemia (mUI/L)/ 22.5, in different soubgroups.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2019
- Study startDec 2019 (estimated)
- Primary completionJun 2020 (estimated)
- Study completionJun 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- 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
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Campania Luigi Vanvitelli
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giuditta Benincasa, University of Campania Luigi Vanvitelli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03903757
- Sponsor's protocol ID
- PRIN2017F8ZB89
- Acronym
- NEWTON
- Status last verified
- Sep 2019
- First submitted
- 31 Mar 2019
- Last updated
- 18 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Network-based Epigenome-Wide associaTion Study in Obesity precisioN Medicine: NEWTON Clinical Trial
- ClinicalTrials.gov ID
- NCT03903757
- Acronym / sponsor ID
- NEWTON / PRIN2017F8ZB89
- Conditions
- Obesity, Type2 Diabetes
- Keywords
- Epigenetics, Network medicine, Personalized therapy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of Campania Luigi VanvitelliUniversity, hospital or other
- Study start
- Dec 2019 (estimated)
- Primary completion
- Jun 2020 (estimated)
- Study completion
- Jun 2021 (estimated)
- First posted
- 4 Apr 2019 (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 prevalence of obesity is increasing and affects more than 650 million people of all ages to become one of the foremost global health threats. Obesity is a complex syndrome that can seriously impair health through a broad range of complications such as cardiovascular disease, type 1 and 2 diabetes (T1D and T2D), cancer, musculoskeletal disorders, psychosocial imbalances, and reduced quality of life, and impacts the treatment of other conditions. Weight reduction has been shown to have a positive effect on these co-morbidities and may increase the effectiveness of treatments specific for other co-morbidities. Lifestyle modification is an integral part of the weight management journey, but is often insufficient on its own, and can be complimented by pharmacological and surgical add-on treatments to achieve greater and more sustainable weight loss, as appropriate. It is likely that there are subgroups of patients that are more suited to certain types of treatment and results risk dilution of perceived efficacy unless these groups are identified and treatment is personalised. The aim of this project is to identify pathophysiologically and clinically meaningful subgroups of obesity by performing Next Generation Sequencing (NGS) approaches and network based algorithm that will allow the optimisation of prevention and treatment of obesity and its complications.
Detailed description
Population study will be recruited at the Clinical Department of Internal Medicine and Specialistics, Department of Advanced Clinical and Surgical Sciences belonging to University of Campania "Luigi Vanvitelli". This study will be performed according to the principles outlined in the Helsinki Declaration. Subcutaneous adipose tissues located in the surgical incision will be withdrawn without the use of surgical devices in order to avoid the degradation of the biological sample from 50 obese subjects (25 obese subjects with Type 2 Diabetes vs 25 obese subjects without Type 2 Diabetes) undergoing bariatric surgery. As controls (n=50) we will recruit subcutaneous adipose tissues from patients without a clinical history of cardiovascular or dysmetabolic diseases undergoing to surgery for stress inguinal hernia. Clinical and demographic characteristics of the study population will be available from datasets generated by physicians.
From tissue samples the genomic DNA and the total RNA will be extracted. Genomic DNA will be extracted by using DNeasy Blood \& Tissue kit (QIAGEN), according to manufacturer protocol. Pooled DNA samples consisting of equal quantities of DNA (2 µg) from cases and controls will be shipped to Genomix4Life Genomics and Bioinformatics Service, to perform a global DNA methylation analysis. For this aim, it will be used the Human Methylation 27K BeadChip platform by using Bisulfite conversion technology (BBRS-Seq). Total RNA will be extracted from tissues using RNeasy Mini Kit (QIAGEN) according to manufacturer protocol. The cDNA library preparation will be performed starting from 4 ug of total RNA by using Illumina TruSeq Libraries and then sequenced at high coverage on the Illumina HiSeq 2500 NGS platform. Nucleic acid concentrations and quality control from Genomix4Life will be assessed by using Nanodrop spectrophotometer (Thermo Fisher Scientific) and Qubit assay (Thermo Fisher Scientific) and TapeStation 4200 (Agilent). The weighted human DNA methylation PPI network (WMPN) will be construct to obtain a obesity interactome in both subgroups (obese and obese with T2D vs controls) based on differentially methylated genes in order to identify putative useful diagnostic biomarkers. The TargetScan algorithm , by searching the conserved seed pairing regions in the 3' untraslated regions (UTR) of genes based on whole genome alignment, will be used to robustly predict miRNA-target gene pairs from the same study population.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Obese subjects with and without T2D | – | Other: DNA methylome and total RNA sequencing |
| control subjects | – | Other: DNA methylome and total RNA sequencing |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Subcutaneous adipose tissues located in the surgical incision will be withdrawn without the use of surgical devices in order to avoid the degradation of the biological sample from 50 obese subjects (25 obese subjects with Type 2 Diabetes vs 25 obese subjects without Type 2 Diabetes) undergoing bariatric surgery. As controls (n=50) we will recruit subcutaneous adipose tissues from patients without a clinical history of cardiovascular or dysmetabolic diseases undergoing to surgery for stress inguinal hernia.
Key inclusion criteria (3 listed)
- Meets the current American Diabetes Association guideline for diagnosis of diabetes (Diabetic group) and obesity
- Must be willing and able to comply with study requirements
- Must indicate their understanding of the study and willingness to participate by signing an appropriate informed consent form
Key exclusion criteria (10 listed)
- History of cancer
- Malignancy disorders
- Active infections
- Chronic or immune-mediated diseases
- Primary disease requiring surgical intervention
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 |
|---|---|---|
| DNA methylome and total RNA sequencingEpigenomics tools combined with bioinformatic analysis to correlate putative useful clinical biomarkers with clinical features | Other | Obese subjects with and without T2D, control subjects |
Primary outcome
DNA methylation pattern in adipose tissues
Time frame: 3 months
Using Methylation 27K BeadChip platform based on Bisulfite conversion technology, DNA methylation profile in adipose tissues of 25 preselected obese subject and 25 obese subjects respect with controls (n=50) will be performed.
Bioinformatics analysis to predict putative novel candidate genes underlying obesity phenotype
Time frame: 6 months
The network-based algorithm "Weighted Human DNA methylation PPI network (WMPN)" will be applied to methylome data in order to obtain a disease module containing the crucial differentially methylated genes both in obese patients and obese patients with T2D compared to controls.
RNA sequencing analysisin adipose tissues
Time frame: 3 months
RNA sequencing analysis by using Illumina HiSeq2000 Next Generatin Sequencing (NGS) platform will be performed for identifying differentially expressed micro-RNA and mRNA target both in obese patients and obese patients with T2D compared to controls.
4 secondary outcomes
ROC curves analysis to evaluate putative DNA methylation/microRNA interactions
Time frame: 12 months
Linear regression analysis and BMI (Kg/m2).
Time frame: 12 months
Linear regression to correlate epigenetic biomarkers with proinflammatory cytokines
Time frame: 12 months
Linear regression to correlate epigenetic biomarkers with HOMA index
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2019.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Obesity and Type2 Diabetes, run by University of Campania Luigi Vanvitelli.
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 3 inclusion and 10 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 18 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DNA methylation pattern in adipose tissues (time frame: 3 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Sep 2019.