Diabetes Mellitus, Type 2NCT05165706
Longitudinal Multi-Omic Profiles to Reveal Mechanisms of Obesity-Mediated Insulin Resistance
A study testing Dietary Intervention Mediterranean Low Carbohydrate Diet, Dietary Intervention Standard Low Carbohydrate Diet and Dietary Intervention Standard Low Fat Diet in people with Diabetes Mellitus, Type 2 and PreDiabetes, run by Stanford University at 1 site in United States.
Trial summary
This 12-week controlled diet and weight intervention study seeks to define the molecular pathways that link excess body weight to the development of insulin resistance (IR). Blood, adipose and stool are sampled at three timepoints; baseline, peak weight (4 weeks) and post weight loss to monitor changes in cellular… Read more about this study
- Who is it for?
- Ages 35 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 2, PreDiabetes, Insulin Resistance
- What is being tested?
- Dietary Intervention Mediterranean Low Carbohydrate Diet, Dietary Intervention Standard Low Carbohydrate Diet and Dietary Intervention Standard Low Fat Diet
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jan 2019to 30 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 35 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 35-65
- BMI 25-35 kg/m2
- Stable body weight
- Nondiabetic
Who cannot join
- Patients with;
- diabetes
- major organ disease
- history of liposuction or bariatric surgery
- active eating or psychiatric disorder
- pregnancy or lactation, heavy alcohol use
Show all 12Show fewer
- recent change in weight (over the past 12 weeks)
- use of weight loss medication, statins, or oral steroids
- Clinical screening exclusions;
- hematocrit < 33%
- fasting glucose >/= 126 mg/dL
- blood pressure >160/100 mmHg
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Dalia Perelman, MS, RD contact
United States1 site, 1 recruiting
- Recruiting
Stanford University
Stanford, California, 94305
Ekrem M Ayhan, BS, 908-619-5381, ayhane@stanford.edu
Dalia Perelman, MS, RD, daliap@stanford.edu
About this study
This 12-week controlled diet and weight intervention study seeks to define the molecular pathways that link excess body weight to the development of insulin resistance (IR). Blood, adipose and stool are sampled at three timepoints; baseline, peak weight (4 weeks) and post weight loss to monitor changes in cellular processes. Additionally, direct insulin sensitivity testing, and radiological measurement of visceral fat and intrahepatic fat content is measured at three timepoints to correlate clinical indices with cellular changes.
Read the detailed description
Obesity has become an epidemic worldwide. Metabolic/cardiovascular complications of obesity are likely related to the fact that obese individuals tend to be insulin resistant (IR). While insulin- mediated glucose uptake (IMGU) correlates with adipose tissue mass, not all obese individuals are IR, and metabolic and cardiovascular profiles of those who are IR vs insulin sensitive (IS) differ significantly. Why one individual who reaches a BMI of 30 kg/m2 will develop IR and another with similar BMI and activity level remains IS is unclear. Furthermore, while insulin sensitivity improves with weight loss, this response varies as well. Given that fat mass per se does not fully explain the obesity contribution to IMGU, itis likely that differential adipocyte function plays a role. With this study, our purpose is to employ an integrated omics strategy to identify analyte/pathway signatures in blood and adipose tissue that characterize IR versus IS states and expand our biological knowledge of the mechanisms underlying IR.
- Conditions
- Diabetes Mellitus, Type 2, PreDiabetes, Insulin Resistance, Obesity, Nonalcoholic Steatohepatitis, Nonalcoholic Fatty Liver
- Being tested
- Dietary Intervention Mediterranean Low Carbohydrate Diet, Dietary Intervention Standard Low Carbohydrate Diet, Dietary Intervention Standard Low Fat Diet
- Keywords
- Metabolomics, Low Fat Diet, Low Carbohydrate Diet, Microbiome
- Medical subject headings
- Diabetes Mellitus, Type 2, Prediabetic State, Insulin Resistance, Obesity, Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dietary Intervention Mediterranean Low Carbohydrate DietBehavioural
Assigned participants will receive instruction by a registered dietitian on a diet that is high in unsaturated fats and low in carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.
Dietary Intervention Standard Low Carbohydrate DietBehavioural
Assigned participants will receive instruction by a registered dietitian on a low carbohydrate diet that is high in fats found in the typical American diet. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.
Dietary Intervention Standard Low Fat DietBehavioural
Assigned participants will receive instruction by a registered dietitian on a low fat diet that is high in complex carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Mediterranean Low Carbohydrate Diet | Experimental | Assigned participants will receive instruction by a registered dietitian on a diet that is high in unsaturated fats and low in carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks. Receives: Behavioral: Dietary Intervention Mediterranean Low Carbohydrate Diet |
| Standard Low Carbohydrate Diet | Experimental | Assigned participants will receive instruction by a registered dietitian on a low carbohydrate diet that is high in fats found in the typical American diet. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks. Receives: Behavioral: Dietary Intervention Standard Low Carbohydrate Diet |
| Low Fat, Healthy Carbohydrate Diet | Experimental | Assigned participants will receive instruction by a registered dietitian on a low fat diet that is high in complex carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks. Receives: Behavioral: Dietary Intervention Standard Low Fat Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline on the 2-stage Steady State Plasma Glucose test
Compare direct measurement of insulin sensitivity after 4 week diet and weight intervention
Measured: Peak weight (4 weeks)
Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio
Compare measurement of abdominal V:S fat volume via computed tomography (CT) after 4 week diet and weight intervention
Measured: Peak weight (4 weeks)
Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition
Compare measurement of liver fat content via magnetic resonance spectroscopy (MRS) after 4 week diet and weight intervention
Measured: Peak weight (4 weeks)
Change from peak weight on the 2-stage Steady State Plasma Glucose test
Compare direct measurement of insulin sensitivity after 8 week diet and weight intervention
Measured: Post-weight loss (8 weeks)
Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio
Compare measurement of abdominal V:S fat volume via computed tomography (CT) after 8 week diet and weight intervention
Measured: Post-weight loss (8 weeks)
Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition
Compare measurement of liver fat content via magnetic resonance spectroscopy (MRS) after 8 week diet and weight intervention
Measured: Post-weight loss (8 weeks)
Measurement of markers of lipid and carbohydrate metabolism and inflammation from adipose mRNA
Compare adipose tissue transcripts such as known MODY transcription factors, defensin chemokine receptors, and platelet activation factors measured by PCR between participants identified as Insulin sensitive (IS) and Insulin resistant (IR) using the 2-stage Steady State Plasma Glucose test.
Measured: Baseline
Quantification of plasma inflammatory cytokine levels in serum samples by Luminex immunoassay
Compare plasma inflammatory cytokine levels in serum samples as measured by Luminex immunoassay between participants identified as Insulin Sensitive (IS) and Insulin Resistant (IR) using the 2-stage Steady State Plasma Glucose test.
Measured: Baseline
Change from baseline in plasma inflammatory cytokine levels in serum samples as measured by Luminex immunoassay
Compare intra-personal levels of plasma inflammatory cytokines as measured by Luminex immunoassay after 4 week diet and weight intervention
Measured: Peak Weight (4 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2021
- Study start31 Jan 2019
- Primary completion30 Nov 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by Stanford UniversityThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tracey McLaughlin, Stanford University
- Investigators
- Tracey McLaughlin, MD, Principal investigator, Stanford University, Department of Medicine, Division of Endocrinology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05165706
- Sponsor's protocol ID
- 40195
- Other IDs
- 5R01DK110186-02
- Status last verified
- Dec 2024
- First submitted
- 3 Jul 2018
- Last updated
- 4 Dec 2024
- 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 4 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Longitudinal Multi-Omic Profiles to Reveal Mechanisms of Obesity-Mediated Insulin Resistance
- ClinicalTrials.gov ID
- NCT05165706
- Acronym / sponsor ID
- 40195
- Conditions
- Diabetes Mellitus, Type 2, PreDiabetes, Insulin Resistance, Obesity, Nonalcoholic Steatohepatitis, Nonalcoholic Fatty Liver
- Keywords
- Metabolomics, Low Fat Diet, Low Carbohydrate Diet, Microbiome
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 31 Jan 2019 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 21 Dec 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.
This 12-week controlled diet and weight intervention study seeks to define the molecular pathways that link excess body weight to the development of insulin resistance (IR). Blood, adipose and stool are sampled at three timepoints; baseline, peak weight (4 weeks) and post weight loss to monitor changes in cellular processes. Additionally, direct insulin sensitivity testing, and radiological measurement of visceral fat and intrahepatic fat content is measured at three timepoints to correlate clinical indices with cellular changes.
Detailed description
Obesity has become an epidemic worldwide. Metabolic/cardiovascular complications of obesity are likely related to the fact that obese individuals tend to be insulin resistant (IR). While insulin- mediated glucose uptake (IMGU) correlates with adipose tissue mass, not all obese individuals are IR, and metabolic and cardiovascular profiles of those who are IR vs insulin sensitive (IS) differ significantly. Why one individual who reaches a BMI of 30 kg/m2 will develop IR and another with similar BMI and activity level remains IS is unclear. Furthermore, while insulin sensitivity improves with weight loss, this response varies as well. Given that fat mass per se does not fully explain the obesity contribution to IMGU, itis likely that differential adipocyte function plays a role. With this study, our purpose is to employ an integrated omics strategy to identify analyte/pathway signatures in blood and adipose tissue that characterize IR versus IS states and expand our biological knowledge of the mechanisms underlying IR.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Mediterranean Low Carbohydrate Diet | Experimental | Behavioral: Dietary Intervention Mediterranean Low Carbohydrate DietAssigned participants will receive instruction by a registered dietitian on a diet that is high in unsaturated fats and low in carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks. |
| Standard Low Carbohydrate Diet | Experimental | Behavioral: Dietary Intervention Standard Low Carbohydrate DietAssigned participants will receive instruction by a registered dietitian on a low carbohydrate diet that is high in fats found in the typical American diet. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks. |
| Low Fat, Healthy Carbohydrate Diet | Experimental | Behavioral: Dietary Intervention Standard Low Fat DietAssigned participants will receive instruction by a registered dietitian on a low fat diet that is high in complex carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks. |
Who may qualify
- Ages
- 35 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 35-65
- BMI 25-35 kg/m2
- Stable body weight
- Nondiabetic
Key exclusion criteria (12 listed)
- Patients with;
- diabetes
- major organ disease
- history of liposuction or bariatric surgery
- active eating or psychiatric disorder
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 |
|---|---|---|
| Dietary Intervention Mediterranean Low Carbohydrate DietAssigned participants will receive instruction by a registered dietitian on a diet that is high in unsaturated fats and low in carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks. | Behavioural | Mediterranean Low Carbohydrate Diet |
| Dietary Intervention Standard Low Carbohydrate DietAssigned participants will receive instruction by a registered dietitian on a low carbohydrate diet that is high in fats found in the typical American diet. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks. | Behavioural | Standard Low Carbohydrate Diet |
| Dietary Intervention Standard Low Fat DietAssigned participants will receive instruction by a registered dietitian on a low fat diet that is high in complex carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks. | Behavioural | Low Fat, Healthy Carbohydrate Diet |
Primary outcome
Change from baseline on the 2-stage Steady State Plasma Glucose test
Time frame: Peak weight (4 weeks)
Compare direct measurement of insulin sensitivity after 4 week diet and weight intervention
Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio
Time frame: Peak weight (4 weeks)
Compare measurement of abdominal V:S fat volume via computed tomography (CT) after 4 week diet and weight intervention
Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition
Time frame: Peak weight (4 weeks)
Compare measurement of liver fat content via magnetic resonance spectroscopy (MRS) after 4 week diet and weight intervention
Change from peak weight on the 2-stage Steady State Plasma Glucose test
Time frame: Post-weight loss (8 weeks)
Compare direct measurement of insulin sensitivity after 8 week diet and weight intervention
Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio
Time frame: Post-weight loss (8 weeks)
Compare measurement of abdominal V:S fat volume via computed tomography (CT) after 8 week diet and weight intervention
Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition
Time frame: Post-weight loss (8 weeks)
Compare measurement of liver fat content via magnetic resonance spectroscopy (MRS) after 8 week diet and weight intervention
Measurement of markers of lipid and carbohydrate metabolism and inflammation from adipose mRNA
Time frame: Baseline
Compare adipose tissue transcripts such as known MODY transcription factors, defensin chemokine receptors, and platelet activation factors measured by PCR between participants identified as Insulin sensitive (IS) and Insulin resistant (IR) using the 2-stage Steady State Plasma Glucose test.
Quantification of plasma inflammatory cytokine levels in serum samples by Luminex immunoassay
Time frame: Baseline
Compare plasma inflammatory cytokine levels in serum samples as measured by Luminex immunoassay between participants identified as Insulin Sensitive (IS) and Insulin Resistant (IR) using the 2-stage Steady State Plasma Glucose test.
Change from baseline in plasma inflammatory cytokine levels in serum samples as measured by Luminex immunoassay
Time frame: Peak Weight (4 weeks)
Compare intra-personal levels of plasma inflammatory cytokines as measured by Luminex immunoassay after 4 week diet and weight intervention
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2024.
- 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.
Dalia Perelman, MS, RD contact
Tracey McLaughlin, MD principal investigator
Stanford University, Department of Medicine, Division of Endocrinology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dietary Intervention Mediterranean Low Carbohydrate Diet, Dietary Intervention Standard Low Carbohydrate Diet and Dietary Intervention Standard Low Fat Diet in people with Diabetes Mellitus, Type 2 and PreDiabetes, run by Stanford 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 12 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: looking for participants now, as of the sponsor's last update on 4 Dec 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ekrem M Ayhan, BS (908-619-5381, ayhane@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline on the 2-stage Steady State Plasma Glucose test (time frame: Peak weight (4 weeks)). The study lists 9 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 4 Dec 2024.