Metabolic Syndrome, Protection AgainstPolyGrapeNCT04053569
Grape Polyphenols and Metabolic Syndrome
A study testing Table Grape supplement in people with Metabolic Syndrome, Protection Against, run by Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis at 1 site in Italy.
Trial summary
Fruits and vegetables are beneficial for patients with metabolic syndrome, a condition characterized by the coexistence of various risk factors (obesity, hypertension, hypercholesterolemia, insulin resistance) that predispose to cardiovascular disease and diabetes. Read more about this study
- Who is it for?
- Ages 30 to 65 years
- Conditions the study is for
- Metabolic Syndrome, Protection Against
- What is being tested?
- Table Grape supplement
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteItaly
- Study dates
- 1 Oct 2019to 1 Nov 2022
- Phase
- Interventional
- 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 30 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age > 30 years and <65 years
- overweight.
Who cannot join
- cardiovascular disease.
- stroke
- treatment with insulin or oral hypoglycemic drugs
- fasting glucose > 126 mg / dl, or casual glycemia > 200 mg / dl
- more than 20 g/day of alcohol intake
- serious medical conditions that may compromise participation in the trial
- subjects following a special diet or involved in a weight-loss program or unable to follow a diet for religious or other reasons.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Polyphenols From a Table Grape on the Lipidomic Profile and Serum LDL Fractions: Possible Implications in the Metabolic Syndrome
Fruits and vegetables are beneficial for patients with metabolic syndrome, a condition characterized by the coexistence of various risk factors (obesity, hypertension, hypercholesterolemia, insulin resistance) that predispose to cardiovascular disease and diabetes. Diets such as the Mediterranean diet, rich in flavonoids and polyphenolic compounds can exert a high anti-inflammatory, antithrombotic and antiproliferative action. Several studies have shown that grape polyphenols exert a crucial protective action against the onset of cardiovascular, neurodegenerative, and cancer diseases. On the other hand, little information is available on the health effects deriving from the consumption of table grapes on cell membranes lipidomic profile. On this basis, the aim of this study is the evaluation of possible changes in lipidomic profile and plasma antioxidant activity induced by a diet enriched with table grape polyphenols.
Read the detailed description
Purified polyphenols extracted by table grape can decrease cell proliferation in vitro and exert anti-atherosclerotic and antithrombotic activities, regulating endothelial function. Literature studies have already evaluated the cytostatic and apoptotic effects produced by table grape extracts from different cultivars, demonstrating a different behavior based on extract composition. The beneficial effects of polyphenols have been attributed exclusively to their direct antioxidant action; however, in recent years it has emerged that polyphenols can interact with intracellular signaling mechanisms, modulating the activity of transcription factors involved in cell lipid metabolism. Lipidomic analysis studies the lipids in a "dynamic" way, monitoring the changes in membrane phospholipids content, caused by inflammation, stress, or malnutrition. These changes can also affect the cellular and plasmatic prothrombotic potential, which results altered in metabolic diseases. Recently, alterations in erythrocytes lipidomic profile have been detected in subjects with steatosis. Moreover, in patients with colorectal cancer patients, the presence of metastases at the time of surgery was associated with an altered profile of fatty acids in the membrane of colonic tissue cells.
Moreover, data in literature show how diet and functional foods can modify serum lipid content, in particular, an important role in the onset of dysmetabolic diseases is undoubtedly played by the different fractions of Low-Density Lipoproteins (LDL). The presence of smaller LDL fractions in the serum, such as fraction 3 and fraction 4, has been associated with the onset of cardiovascular disease and myocardial infarctions. Therefore, understanding the molecular mechanisms underlying the effects of nutraceuticals is essential to develop prevention and intervention strategies on subjects at risk for metabolic syndrome.
On this basis, the aim of this study is the evaluation of possible changes happening in lipidomic profile, plasma antioxidant activity and plasma prothrombotic potential induced by a diet enriched with table grape polyphenols in subjects with metabolic syndrome.
- Conditions
- Metabolic Syndrome, Protection Against
- Being tested
- Table Grape supplement
- Keywords
- polyphenols, diet, lipidomics, metabolic syndrome
- Medical subject headings
- Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Table Grape supplementDietary supplement
5g/Kg of table grape for four weeks with dietary recommendations along with a strict restriction of fruits and limitation of other foods containing polyphenols.
| Study group | Role | What they receive |
|---|---|---|
| Diet with table grape | Experimental | Table grape (5g/Kg) administered for four weeks with dietary recommendations. A strict restriction of fruits and the limitation of other foods containing polyphenols will be necessary. Receives: Dietary Supplement: Table Grape supplement |
| Specific dietary advice | No intervention | Dietary recommendations (such as limitation of alcohol, caffeine), and low consumption of fruits. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in serum concentrations (mg/dL) of cholesterol, triglycerides, glucose
Blood samples will be taken after at least 12 hours of fasting and the concentrations of cholesterol. triglycerides, and glucose will be assessed according to the standard laboratory methods (commercially available kits).
Measured: Before the start of the study (time 0), after four weeks (time 1) and after eight weeks (time 2)
Changes in blood concentration of fatty acids (stearic acid, oleic acid, arachidonic acid, eicosaepentanoic acid) expressed as percentage (%)
All human blood samples are treated with chloroform: methanol (2:1, v/v), and the samples are centrifuged. The lower layer, containing fatty acids, are removed with care, replaced in a new tube and dried by a centrifugal evaporator. The fatty acid methyl ester (FAME) is obtained by adding toluene and BF3. Samples are collected and transferred into a vial and analyzed by gas chromatography.
Measured: Before the start of the study (time 0) and after eight weeks (time 2)
Changes in serum concentration of single subfractions of LDL (expressed as mg/dL)
Small dense LDL analysis: Small dense Lipoproteins (sdLDL) are assayed using Lipoprint LDL System (Quantimetrix, USA). Each serum sample is applied on high resolution polyacrylamide gel tube in order to separate LDL fractions and subfractions by electrophoresis. The resolved lipoproteins bands are scanned and analyzed.
Measured: Before the start of the study (time 0) and after eight weeks (time 2)
Secondary outcomes (3)
Changes in the concentrations of radical monocation of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) expressed as µM Trolox equivalents/g of dry weight
The ABTS assay will be performed using the commercially available ZENBIO-AOX-1 kit.
Measured: Before the start of the study (time 0), after four weeks (time 1) and after eight weeks (time 2)
Changes in plasma prothrombotic potential
The plasma prothrombotic potential will be evaluated using a functional test able to monitor the entire kinetics of thrombin generation, including its inactivation by plasma physiological inhibitors. In these tests, the coagulation will be activated by purified tissue factor.
Measured: Before the start of the study (time 0), after four weeks (time 1) and after eight weeks (time 2)
Changes in plasma grape miRNA content
Total serum RNA, including Small RNAs, will be extracted from plasma (200µL) of the subjects involved in the study using the miRNeasy Mini Kit (QIAGEN). After checking the concentration and quality, the effective presence of miRNAs will be verified by retro-transcription with a specific miRNA kit (TaqMan miRNA Reverse Transcription kit - Life Technologies) using Real Time-polymerase chain reaction (PCR) method.
Measured: Before the start of the study (time 0) (time 1) and after eight weeks (time 2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2019
- Study start1 Oct 2019
- Primary completion1 Nov 2020
- Study completion1 Nov 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Metabolic Syndrome, Protection AgainstStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, single-blind clinical trial
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francesco Russo, Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
- Investigators
- Maria Notarnicola, ScD, Principal investigator, IRCCS "Saverio de Bellis" Castellana Grotte
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04053569
- Sponsor's protocol ID
- RC2019019
- Acronym
- PolyGrape
- Status last verified
- Mar 2022
- First submitted
- 6 Aug 2019
- Last updated
- 22 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Li B, Zhang C, Zhan YT. Nonalcoholic Fatty Liver Disease Cirrhosis: A Review of Its Epidemiology, Risk Factors, Clinical Presentation, Diagnosis, Management, and Prognosis. Can J Gastroenterol Hepatol. 2018 Jul 2;2018:2784537. doi: 10.1155/2018/2784537. eCollection 2018.
PubMed 30065915Liu YC, Chen WL, Kung WH, Huang HD. Plant miRNAs found in human circulating system provide evidences of cross kingdom RNAi. BMC Genomics. 2017 Mar 14;18(Suppl 2):112. doi: 10.1186/s12864-017-3502-3.
PubMed 28361700Mlotshwa S, Pruss GJ, MacArthur JL, Endres MW, Davis C, Hofseth LJ, Pena MM, Vance V. A novel chemopreventive strategy based on therapeutic microRNAs produced in plants. Cell Res. 2015 Apr;25(4):521-4. doi: 10.1038/cr.2015.25. Epub 2015 Feb 27. No abstract available.
PubMed 25721325Notarnicola M, Caruso MG, Tutino V, Bonfiglio C, Cozzolongo R, Giannuzzi V, De Nunzio V, De Leonardis G, Abbrescia DI, Franco I, Intini V, Mirizzi A, Osella AR. Significant decrease of saturation index in erythrocytes membrane from subjects with non-alcoholic fatty liver disease (NAFLD). Lipids Health Dis. 2017 Aug 23;16(1):160. doi: 10.1186/s12944-017-0552-0.
PubMed 28830448Ammollo CT, Semeraro F, Milella RA, Antonacci D, Semeraro N, Colucci M. Grape intake reduces thrombin generation and enhances plasma fibrinolysis. Potential role of circulating procoagulant microparticles. J Nutr Biochem. 2017 Dec;50:66-73. doi: 10.1016/j.jnutbio.2017.08.012. Epub 2017 Sep 1.
PubMed 29040837
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Polyphenols From a Table Grape on the Lipidomic Profile and Serum LDL Fractions: Possible Implications in the Metabolic Syndrome
- ClinicalTrials.gov ID
- NCT04053569
- Acronym / sponsor ID
- PolyGrape / RC2019019
- Conditions
- Metabolic Syndrome, Protection Against
- Keywords
- polyphenols, diet, lipidomics, metabolic syndrome
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de BellisUniversity, hospital or other
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 1 Nov 2020 (actual)
- Study completion
- 1 Nov 2022 (estimated)
- First posted
- 12 Aug 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.
Fruits and vegetables are beneficial for patients with metabolic syndrome, a condition characterized by the coexistence of various risk factors (obesity, hypertension, hypercholesterolemia, insulin resistance) that predispose to cardiovascular disease and diabetes. Diets such as the Mediterranean diet, rich in flavonoids and polyphenolic compounds can exert a high anti-inflammatory, antithrombotic and antiproliferative action. Several studies have shown that grape polyphenols exert a crucial protective action against the onset of cardiovascular, neurodegenerative, and cancer diseases. On the other hand, little information is available on the health effects deriving from the consumption of table grapes on cell membranes lipidomic profile. On this basis, the aim of this study is the evaluation of possible changes in lipidomic profile and plasma antioxidant activity induced by a diet enriched with table grape polyphenols.
Detailed description
Purified polyphenols extracted by table grape can decrease cell proliferation in vitro and exert anti-atherosclerotic and antithrombotic activities, regulating endothelial function. Literature studies have already evaluated the cytostatic and apoptotic effects produced by table grape extracts from different cultivars, demonstrating a different behavior based on extract composition. The beneficial effects of polyphenols have been attributed exclusively to their direct antioxidant action; however, in recent years it has emerged that polyphenols can interact with intracellular signaling mechanisms, modulating the activity of transcription factors involved in cell lipid metabolism. Lipidomic analysis studies the lipids in a "dynamic" way, monitoring the changes in membrane phospholipids content, caused by inflammation, stress, or malnutrition. These changes can also affect the cellular and plasmatic prothrombotic potential, which results altered in metabolic diseases. Recently, alterations in erythrocytes lipidomic profile have been detected in subjects with steatosis. Moreover, in patients with colorectal cancer patients, the presence of metastases at the time of surgery was associated with an altered profile of fatty acids in the membrane of colonic tissue cells.
Moreover, data in literature show how diet and functional foods can modify serum lipid content, in particular, an important role in the onset of dysmetabolic diseases is undoubtedly played by the different fractions of Low-Density Lipoproteins (LDL). The presence of smaller LDL fractions in the serum, such as fraction 3 and fraction 4, has been associated with the onset of cardiovascular disease and myocardial infarctions. Therefore, understanding the molecular mechanisms underlying the effects of nutraceuticals is essential to develop prevention and intervention strategies on subjects at risk for metabolic syndrome.
On this basis, the aim of this study is the evaluation of possible changes happening in lipidomic profile, plasma antioxidant activity and plasma prothrombotic potential induced by a diet enriched with table grape polyphenols in subjects with metabolic syndrome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Randomized, single-blind clinical trial
| Arm | Type | Receives |
|---|---|---|
| Diet with table grape | Experimental | Dietary Supplement: Table Grape supplementTable grape (5g/Kg) administered for four weeks with dietary recommendations. A strict restriction of fruits and the limitation of other foods containing polyphenols will be necessary. |
| Specific dietary advice | No intervention | –Dietary recommendations (such as limitation of alcohol, caffeine), and low consumption of fruits. |
Who may qualify
- Ages
- 30 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- age > 30 years and <65 years
- overweight.
Key exclusion criteria (7 listed)
- cardiovascular disease.
- stroke
- treatment with insulin or oral hypoglycemic drugs
- fasting glucose > 126 mg / dl, or casual glycemia > 200 mg / dl
- more than 20 g/day of alcohol intake
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 |
|---|---|---|
| Table Grape supplement5g/Kg of table grape for four weeks with dietary recommendations along with a strict restriction of fruits and limitation of other foods containing polyphenols. | Dietary supplement | Diet with table grape |
Primary outcome
Changes in serum concentrations (mg/dL) of cholesterol, triglycerides, glucose
Time frame: Before the start of the study (time 0), after four weeks (time 1) and after eight weeks (time 2)
Blood samples will be taken after at least 12 hours of fasting and the concentrations of cholesterol. triglycerides, and glucose will be assessed according to the standard laboratory methods (commercially available kits).
Changes in blood concentration of fatty acids (stearic acid, oleic acid, arachidonic acid, eicosaepentanoic acid) expressed as percentage (%)
Time frame: Before the start of the study (time 0) and after eight weeks (time 2)
All human blood samples are treated with chloroform: methanol (2:1, v/v), and the samples are centrifuged. The lower layer, containing fatty acids, are removed with care, replaced in a new tube and dried by a centrifugal evaporator. The fatty acid methyl ester (FAME) is obtained by adding toluene and BF3. Samples are collected and transferred into a vial and analyzed by gas chromatography.
Changes in serum concentration of single subfractions of LDL (expressed as mg/dL)
Time frame: Before the start of the study (time 0) and after eight weeks (time 2)
Small dense LDL analysis: Small dense Lipoproteins (sdLDL) are assayed using Lipoprint LDL System (Quantimetrix, USA). Each serum sample is applied on high resolution polyacrylamide gel tube in order to separate LDL fractions and subfractions by electrophoresis. The resolved lipoproteins bands are scanned and analyzed.
3 secondary outcomes
Changes in the concentrations of radical monocation of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) expressed as µM Trolox equivalents/g of dry weight
Time frame: Before the start of the study (time 0), after four weeks (time 1) and after eight weeks (time 2)
Changes in plasma prothrombotic potential
Time frame: Before the start of the study (time 0), after four weeks (time 1) and after eight weeks (time 2)
Changes in plasma grape miRNA content
Time frame: Before the start of the study (time 0) (time 1) and after eight weeks (time 2)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2022.
- Background: PubMed 30065915Li B, Zhang C, Zhan YT. Nonalcoholic Fatty Liver Disease Cirrhosis: A Review of Its Epidemiology, Risk Factors, Clinical Presentation, Diagnosis, Management, and Prognosis. Can J Gastroenterol Hepatol. 2018 Jul 2;2018:2784537. doi: 10.1155/2018/2784537. eCollection 2018.
- Background: PubMed 28361700Liu YC, Chen WL, Kung WH, Huang HD. Plant miRNAs found in human circulating system provide evidences of cross kingdom RNAi. BMC Genomics. 2017 Mar 14;18(Suppl 2):112. doi: 10.1186/s12864-017-3502-3.
- Background: PubMed 25721325Mlotshwa S, Pruss GJ, MacArthur JL, Endres MW, Davis C, Hofseth LJ, Pena MM, Vance V. A novel chemopreventive strategy based on therapeutic microRNAs produced in plants. Cell Res. 2015 Apr;25(4):521-4. doi: 10.1038/cr.2015.25. Epub 2015 Feb 27. No abstract available.
- Background: PubMed 28830448Notarnicola M, Caruso MG, Tutino V, Bonfiglio C, Cozzolongo R, Giannuzzi V, De Nunzio V, De Leonardis G, Abbrescia DI, Franco I, Intini V, Mirizzi A, Osella AR. Significant decrease of saturation index in erythrocytes membrane from subjects with non-alcoholic fatty liver disease (NAFLD). Lipids Health Dis. 2017 Aug 23;16(1):160. doi: 10.1186/s12944-017-0552-0.
- Background: PubMed 29040837Ammollo CT, Semeraro F, Milella RA, Antonacci D, Semeraro N, Colucci M. Grape intake reduces thrombin generation and enhances plasma fibrinolysis. Potential role of circulating procoagulant microparticles. J Nutr Biochem. 2017 Dec;50:66-73. doi: 10.1016/j.jnutbio.2017.08.012. Epub 2017 Sep 1.
- 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.
Maria Notarnicola, ScD principal investigator
IRCCS "Saverio de Bellis" Castellana Grotte
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Table Grape supplement in people with Metabolic Syndrome, Protection Against, run by Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis at 1 site in Italy.
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 2 inclusion and 7 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 22 Mar 2022. 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 Italy. 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?
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?
Changes in serum concentrations (mg/dL) of cholesterol, triglycerides, glucose (time frame: Before the start of the study (time 0), after four weeks (time 1) and after eight weeks (time 2)). 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?
On the ClinicalTrials.gov record for NCT04053569, which also lists 5 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 22 Mar 2022.