Type2 DiabetesNCT03458494
The TCF7L2 Gene: Dietary Prevention of T2DM
A study testing Mediterranean Diet and Low-fat diet in people with Type2 Diabetes and Glucose, High Blood, run by Tufts University at 1 site in United States.
Trial summary
Nutrients and chemicals in food are able to regulate expression of genetic elements. Gene-nutrient interaction in response specific diets can increase an individual's risk, shifting the individual from health toward the development of chronic disease. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Type2 Diabetes, Glucose, High Blood
- What is being tested?
- Mediterranean Diet and Low-fat diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2018to 30 Apr 2020
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men and women.
- 18 years or older.
- Women who are not pregnant.
- A BMI ranging between 27 and 34
Who cannot join
- Unexplained elevation in serum transaminases (i.e. >1.5 times the upper limit of normal) or with evidence of active liver disease, including primary biliary cirrhosis or pre-existing gallbladder disease.
- Severe renal dysfunction (serum creatinine >2.0mg/dL).
- Excessive alcohol consumption (>2 drinks/day).
- Preexisting CVD.
- Stable exertional angina pectoris requiring sublingual nitroglycerin within the prior 3 months.
- Uncontrolled T2D (fasting glucose >126 mg/dl) or other significant endocrine disease.
Show all 16Show fewer
- Uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg).
- History of pancreatitis within 1 yr. prior to screening.
- Subjects on lipid-lowering or diabetes medications.
- Smoking.
- Pregnancy.
- Body mass index (BMI) below 27 or greater than 34 kg/m2
- Participants will also be excluded for drug abuse, extreme dietary habits, multiple food allergies, extreme levels of physical or athletic activity, or by changes in body weight >20 lbs. during the last 6 months.
- Inability to follow any of the experimental diets or to perform the sampling required for this study.
- Thyroid diseases.
- Use of omega-3 supplements (unless it is discontinued one month prior to the beginning of the study).
Trial locations and contacts
1 site in 1 country.
United States1 site
JM-USDA Human Nutrition Research Center on Aging at Tufts University
Boston, Massachusetts, 02111
About this study
Official title: The TCF7L2 Gene: Nutrigenomics and Dietary Prevention of Type 2 Diabetes
Nutrients and chemicals in food are able to regulate expression of genetic elements. Gene-nutrient interaction in response specific diets can increase an individual's risk, shifting the individual from health toward the development of chronic disease. The Transcription Factor 7 Like 2 (TCF7L2) gene may either put individuals at risk for or protect from Type 2 diabetes mellitus in the presence of certain foods. The main purpose of this four-week study is to examine diet-induced gene-nutrient interaction, with a focus on glucose, insulin, inflammation (CRP) and the plasma metabolome in individuals who have either the CC or the TT form of the rs7903146 single nucleotide polymorphism (SNP) (C/T) within the TCF7L2 gene. The (2) one-week study diets, one Mediterranean diet (MedDiet) based and the other low-fat based will be separated by a (1) week return to a regular habitual diet.
Read the detailed description
Type 2 diabetes (T2DM) is associated with increased morbidity and mortality, and its growing prevalence represents a major public health concern. T2D results from a combination of genetics and the exposure to external factors (i.e., diet, exercise, and stress). Multiple T2D-related genes have been identified, but they explain only ~10% of the estimated T2D heritability. Therefore, it has been proposed that interactions between genetic and environmental factors contribute to the missing heritability. The identification of these gene-environment interactions could provide a breakthrough in the prevention of T2D and its complications through the implementation of novel nutrigenomics approaches.
The rs7903146 single nucleotide polymorphism (SNP) (C/T) within the TCF7L2 gene is the most replicated T2D-associated SNP. However, the mechanism associating TCF7L2 with T2D remains unknown. Moreover, there is little knowledge of how diet modulates this association. A better understanding is crucial for improving existing, or designing new interventions for T2D prevention.
The current knowledge supports the notion that subjects homozygous for the deleterious allele (TT) have a higher risk of T2D than subjects homozygous for the common allele (CC). Furthermore, there is a gene-diet interaction between this SNP and Mediterranean diet (MedDiet) on fasting glucose and lipids. Thus, a higher MedDiet adherence neutralizes the effects of the deleterious TT genotype. Moreover, after ~5 years, TT subjects consuming a low-fat diet have higher incidence of stroke than CC subjects, whereas this association is annulled in TT subjects consuming a MedDiet. the objective of this study is to validate these findings under practical conditions similar to those encountered in clinical practice and to identify biological mechanisms involved in such interactions.
For this purpose, a four-week study will be conducted to examine diet-induced gene-nutrient interaction, with a focus on glucose, insulin, and inflammation (CRP) in individuals who have either the CC or the TT form of the rs7903146 single nucleotide polymorphism (SNP) (C/T) within the TCF7L2 gene. The (2) one-week study diets, one Mediterranean diet (MedDiet) based and the other low-fat based will be separated by a (1) week return to a regular habitual diet.
The specific aims include:
- To investigate whether the TCF7L2-by-diet interaction in relation to T2D and cardiovascular disease (CVD) risk factors can be validated in the context of a more realistic scenario of personalized dietary advice based on genetic information (nutrigenomics).
- To elucidate the molecular mechanisms responsible for these gene-by-diet interactions using deep phenotyping (i.e., metabolomics).
The hypothesis is that genetics can offer precise information about which healthy diet (low-fat or Mediterranean) can deliver real benefits on an individual basis.
- Conditions
- Type2 Diabetes, Glucose, High Blood
- Being tested
- Mediterranean Diet, Low-fat diet
- Keywords
- type 2 diabetes, glucose, insulin, CRP, Metabolomics, gene-diet interaction, TCF7L2
- Medical subject headings
- Diabetes Mellitus, Type 2, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mediterranean DietOther
Participants will receive meals traditionally consumed in Mediterranean countries
Low-fat dietOther
Participants will receive meals with a low content of total fat.
| Study group | Role | What they receive |
|---|---|---|
| Mediterranean Diet | Experimental | during one week participants will receive food products common in the diet of Mediterranean populations Receives: Other: Mediterranean Diet |
| Low-fat diet | Experimental | during one week participants will receive food products low in fat content Receives: Other: Low-fat diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucose
Plasma glucose levels (mg/dl) will be measured in the fasting state during each one of the intervention phases (the Mediterranean and low-fat diets) in participants with the TT and CC genotypes at the TCF7L2 rs7903146 SNP
Measured: 1 week per intervention arm
Secondary outcomes (6)
Insulin
Fasting plasma insulin levels (pmol/l) will be measured in the fasting state during each one of the intervention phases (the Mediterranean and low-fat diets) in participants with the TT and CC genotypes at the TCF7L2 rs7903146 SNP
Measured: 1 week per intervention arm
Metabolomics
The response of plasma metabolites to the Mediterranean and low-fat diets diet) will be measured using ultra high-performance liquid chromatography/tandem accurate mass spectrometry (UHPLC/MS/MS) during each one of the intervention phases (the Mediterranean and low-fat diets) in participants with the TT and CC genotypes at the TCF7L2 rs7903146 SNP
Measured: 1 week per intervention arm
Very low density lipoproteins (VLDL)
Fasting plasma concentrations of VLDL in mg/dl, assessed by proton nuclear magnetic resonance (NMR) spectroscopy will be measured during each one of the intervention phases (the Mediterranean and low-fat diets) in participants with the TT and CC genotypes at the TCF7L2 rs7903146 SNP
Measured: 1 week per intervention arm
Low-density lipoproteins (LDL)
Fasting plasma concentrations of LDL in mg/dl, assessed by proton nuclear magnetic resonance (NMR) spectroscopy will be measured during each one of the intervention phases (the Mediterranean and low-fat diets) in participants with the TT and CC genotypes at the TCF7L2 rs7903146 SNP
Measured: 1 week per intervention arm
High-density lipoproteins (HDL)
Fasting plasma concentrations of HDL in mg/dl, assessed by proton nuclear magnetic resonance (NMR) spectroscopy will be measured during each one of the intervention phases (the Mediterranean and low-fat diets) in participants with the TT and CC genotypes at the TCF7L2 rs7903146 SNP
Measured: 1 week per intervention arm
CRP
Plasma C-reactive protein (mg/dl) will be measured in the fasting state during each one of the intervention phases (the Mediterranean and low-fat diets) in participants with the TT and CC genotypes at the TCF7L2 rs7903146 SNP
Measured: 1 week per intervention arm
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2018
- Study start15 Feb 2018
- Primary completion30 Apr 2020
- Study completion30 Apr 2020
Why it stopped: COVID-19
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type2 DiabetesStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- randomized crossover dietary intervention
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tufts University
- Sponsor type
- University, hospital or other
- Collaborators
- Allen Foundation Inc.
- Responsible party
- Principal investigator, Jose Ordovas, Tufts University
- Investigators
- Jose M Ordovas, PHD, Principal investigator, Tufts University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03458494
- Sponsor's protocol ID
- TCF7L2_2965
- Status last verified
- Aug 2024
- First submitted
- 24 Feb 2018
- Last updated
- 4 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plans are in place to share individual participant data (IPD) with other researchers others than those involved in the study. However, the study investigators are open to collaborations that do not include sharing IPD
Publications
Corella D, Carrasco P, Sorli JV, Estruch R, Rico-Sanz J, Martinez-Gonzalez MA, Salas-Salvado J, Covas MI, Coltell O, Aros F, Lapetra J, Serra-Majem L, Ruiz-Gutierrez V, Warnberg J, Fiol M, Pinto X, Ortega-Azorin C, Munoz MA, Martinez JA, Gomez-Gracia E, Gonzalez JI, Ros E, Ordovas JM. Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: a randomized controlled trial in a high-cardiovascular-risk population. Diabetes Care. 2013 Nov;36(11):3803-11. doi: 10.2337/dc13-0955. Epub 2013 Aug 13.
PubMed 23942586Lai CQ, Gervis JE, Parnell LD, Lichtenstein AH, Ordovas JM. Changes in triglyceride-rich lipoprotein particle profiles in response to one-week on a low fat or Mediterranean diet by TCF7L2 rs7903146 genotype: a randomized crossover dietary intervention trial. Genes Nutr. 2025 Mar 6;20(1):4. doi: 10.1186/s12263-025-00763-y.
PubMed 40050721
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The TCF7L2 Gene: Nutrigenomics and Dietary Prevention of Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT03458494
- Acronym / sponsor ID
- TCF7L2_2965
- Conditions
- Type2 Diabetes, Glucose, High Blood
- Keywords
- type 2 diabetes, glucose, insulin, CRP, Metabolomics, gene-diet interaction, TCF7L2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: COVID-19
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Tufts UniversityUniversity, hospital or other
- Collaborators
- Allen Foundation Inc.
- Study start
- 15 Feb 2018 (actual)
- Primary completion
- 30 Apr 2020 (actual)
- Study completion
- 30 Apr 2020 (actual)
- First posted
- 8 Mar 2018 (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.
Nutrients and chemicals in food are able to regulate expression of genetic elements. Gene-nutrient interaction in response specific diets can increase an individual's risk, shifting the individual from health toward the development of chronic disease. The Transcription Factor 7 Like 2 (TCF7L2) gene may either put individuals at risk for or protect from Type 2 diabetes mellitus in the presence of certain foods. The main purpose of this four-week study is to examine diet-induced gene-nutrient interaction, with a focus on glucose, insulin, inflammation (CRP) and the plasma metabolome in individuals who have either the CC or the TT form of the rs7903146 single nucleotide polymorphism (SNP) (C/T) within the TCF7L2 gene. The (2) one-week study diets, one Mediterranean diet (MedDiet) based and the other low-fat based will be separated by a (1) week return to a regular habitual diet.
Detailed description
Type 2 diabetes (T2DM) is associated with increased morbidity and mortality, and its growing prevalence represents a major public health concern. T2D results from a combination of genetics and the exposure to external factors (i.e., diet, exercise, and stress). Multiple T2D-related genes have been identified, but they explain only ~10% of the estimated T2D heritability. Therefore, it has been proposed that interactions between genetic and environmental factors contribute to the missing heritability. The identification of these gene-environment interactions could provide a breakthrough in the prevention of T2D and its complications through the implementation of novel nutrigenomics approaches.
The rs7903146 single nucleotide polymorphism (SNP) (C/T) within the TCF7L2 gene is the most replicated T2D-associated SNP. However, the mechanism associating TCF7L2 with T2D remains unknown. Moreover, there is little knowledge of how diet modulates this association. A better understanding is crucial for improving existing, or designing new interventions for T2D prevention.
The current knowledge supports the notion that subjects homozygous for the deleterious allele (TT) have a higher risk of T2D than subjects homozygous for the common allele (CC). Furthermore, there is a gene-diet interaction between this SNP and Mediterranean diet (MedDiet) on fasting glucose and lipids. Thus, a higher MedDiet adherence neutralizes the effects of the deleterious TT genotype. Moreover, after ~5 years, TT subjects consuming a low-fat diet have higher incidence of stroke than CC subjects, whereas this association is annulled in TT subjects consuming a MedDiet. the objective of this study is to validate these findings under practical conditions similar to those encountered in clinical practice and to identify biological mechanisms involved in such interactions.
For this purpose, a four-week study will be conducted to examine diet-induced gene-nutrient interaction, with a focus on glucose, insulin, and inflammation (CRP) in individuals who have either the CC or the TT form of the rs7903146 single nucleotide polymorphism (SNP) (C/T) within the TCF7L2 gene. The (2) one-week study diets, one Mediterranean diet (MedDiet) based and the other low-fat based will be separated by a (1) week return to a regular habitual diet.
The specific aims include:
- To investigate whether the TCF7L2-by-diet interaction in relation to T2D and cardiovascular disease (CVD) risk factors can be validated in the context of a more realistic scenario of personalized dietary advice based on genetic information (nutrigenomics).
- To elucidate the molecular mechanisms responsible for these gene-by-diet interactions using deep phenotyping (i.e., metabolomics).
The hypothesis is that genetics can offer precise information about which healthy diet (low-fat or Mediterranean) can deliver real benefits on an individual basis.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (investigator)
- Number of arms
- 2
- Model description
- randomized crossover dietary intervention
| Arm | Type | Receives |
|---|---|---|
| Mediterranean Diet | Experimental | Other: Mediterranean Dietduring one week participants will receive food products common in the diet of Mediterranean populations |
| Low-fat diet | Experimental | Other: Low-fat dietduring one week participants will receive food products low in fat content |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Men and women.
- 18 years or older.
- Women who are not pregnant.
- A BMI ranging between 27 and 34
Key exclusion criteria (16 listed)
- Unexplained elevation in serum transaminases (i.e. >1.5 times the upper limit of normal) or with evidence of active liver disease, including primary biliary cirrhosis or pre-existing gallbladder disease.
- Severe renal dysfunction (serum creatinine >2.0mg/dL).
- Excessive alcohol consumption (>2 drinks/day).
- Preexisting CVD.
- Stable exertional angina pectoris requiring sublingual nitroglycerin within the prior 3 months.
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 |
|---|---|---|
| Mediterranean DietParticipants will receive meals traditionally consumed in Mediterranean countries | Other | Mediterranean Diet |
| Low-fat dietParticipants will receive meals with a low content of total fat. | Other | Low-fat diet |
Primary outcome
Glucose
Time frame: 1 week per intervention arm
Plasma glucose levels (mg/dl) will be measured in the fasting state during each one of the intervention phases (the Mediterranean and low-fat diets) in participants with the TT and CC genotypes at the TCF7L2 rs7903146 SNP
6 secondary outcomes
Insulin
Time frame: 1 week per intervention arm
Metabolomics
Time frame: 1 week per intervention arm
Very low density lipoproteins (VLDL)
Time frame: 1 week per intervention arm
Low-density lipoproteins (LDL)
Time frame: 1 week per intervention arm
High-density lipoproteins (HDL)
Time frame: 1 week per intervention arm
CRP
Time frame: 1 week per intervention arm
Results and safety
The study was stopped early (reason given: COVID-19). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2024.
- Background: PubMed 23942586Corella D, Carrasco P, Sorli JV, Estruch R, Rico-Sanz J, Martinez-Gonzalez MA, Salas-Salvado J, Covas MI, Coltell O, Aros F, Lapetra J, Serra-Majem L, Ruiz-Gutierrez V, Warnberg J, Fiol M, Pinto X, Ortega-Azorin C, Munoz MA, Martinez JA, Gomez-Gracia E, Gonzalez JI, Ros E, Ordovas JM. Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: a randomized controlled trial in a high-cardiovascular-risk population. Diabetes Care. 2013 Nov;36(11):3803-11. doi: 10.2337/dc13-0955. Epub 2013 Aug 13.
- Derived from this study: PubMed 40050721Lai CQ, Gervis JE, Parnell LD, Lichtenstein AH, Ordovas JM. Changes in triglyceride-rich lipoprotein particle profiles in response to one-week on a low fat or Mediterranean diet by TCF7L2 rs7903146 genotype: a randomized crossover dietary intervention trial. Genes Nutr. 2025 Mar 6;20(1):4. doi: 10.1186/s12263-025-00763-y.
- Individual participant dataSharing planned: No. No plans are in place to share individual participant data (IPD) with other researchers others than those involved in the study. However, the study investigators are open to collaborations that do not include sharing IPD
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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.
Jose M Ordovas, PHD principal investigator
Tufts University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mediterranean Diet and Low-fat diet in people with Type2 Diabetes and Glucose, High Blood, run by Tufts University at 1 site in United States.
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 4 inclusion and 16 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: stopped early, as of the sponsor's last update on 4 Sep 2024. 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 United States. 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?
The study was stopped early (reason given: COVID-19). 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?
Glucose (time frame: 1 week per intervention arm). 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 NCT03458494, which also lists 2 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 4 Sep 2024.