Type 2 DiabetesLiver-CGNCT04405895
Effect of Meal Timing in T2D on Hepatocytes SRIT1 and Clock Genes
A study testing Breakfast Diet and Allday Diet in people with Type 2 Diabetes and Obesity, run by Tel Aviv University at 1 site in Israel.
Trial summary
This study is undertaken to explore in T2D, the effect of meal timing on serum induced SIRT1 and Clock Genes mRNA expression in cultured hepatocytes. Fasting serum samples were collected from T2D participants, following two different meal timing schedules, either a diet with large breakfast and lunch with small dinner… Read more about this study
- Who is it for?
- Ages 30 to 70 years
- Conditions the study is for
- Type 2 Diabetes, Obesity
- What is being tested?
- Breakfast Diet and Allday Diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteIsrael
- Study dates
- 31 May 2020to 20 Oct 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 30 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- T2D patients with stable treatment for at least 3 month preceding the study.
- HgA1c >7.5 %.
- Age > 30 years.
- BMI: 27-34 kg/m2.
- Treatment with antidiabetic drugs (i.e. metformin, DPP4 inhibitors, glinides) and GLP-1 analogs, will be allowed
- Anti-hypertensive treatment will be allowed.
- Lipid-lowering medication also allowed
Who cannot join
- Type 1 diabetes.
- Major illnesses (liver, heart, kidney, infectious, neurological, psychiatric, immunological, active malignancy).
- Change in weight of > 4.5 kg within 3 month prior the diet onset.
- Night or rotating shift workers.
- Those who crossed more than 2 time zones during 2-week period prior to study onset.
Trial locations and contacts
1 site in 1 country.
Israel1 site
Wolfson Medical Center
Holon, Please Select, 58100
Daniela Jakubowicz, MD, 0508105552, daniela.jak@gmail.com
Zohar Landau, MD, 972544822792, landau.zohar@gmail.com
About this study
Official title: Effect Meal Timing in Type 2 Diabetes on Serum Induced SIRT1 and Clock Gene Expression in Hepatocytes
This study is undertaken to explore in T2D, the effect of meal timing on serum induced SIRT1 and Clock Genes mRNA expression in cultured hepatocytes. Fasting serum samples were collected from T2D participants, following two different meal timing schedules, either a diet with large breakfast and lunch with small dinner Breakfast Diet (3Mdiet) or an isocaloric diet with 6 small meals evenly distributed along the day Allday Diet (6Mdiet). The researchers will use an ex-vivo/in-vitro approach in which cultured medium will be conditioned with the fasted human serum collected from the two groups of T2D participants at baseline, after 2 weeks and after 12 week of the diet intervention.
Read the detailed description
The timing of many physiological processes, including glucose metabolism, is coordinated by the circadian clock gene system. The circadian clock regulation, optimize glucose metabolism for the consumption of high energy and carbohydrate (CH) meals in the early hours of the day and for fasting at evening and night. Circadian disruption which occurs when the meal timing is not aligned with the circadian clock rhythms like skipping breakfast, overeating CH at night or eating CH all day, lead to desynchronized clock genes and can result in adverse health outcomes like insulin resistance, obesity hyperglycemia and T2D. Although the clock genes are disseminated in almost all peripheral tissues, those localized in the liver, are particularly important for the regulation of glucose metabolism, influencing the enzymatic determinants of the hepatic glucose output, by enhancing glycogen storage and suppressing nocturnal hepatic glucose production (glycogenolysis and gluconeogenesis sequentially).Therefore, the disruption of the hepatic clock genes lead to fasting, nocturnal, and to postprandial hyperglycemia in T2D. The researchers had previously shown in T2D, that compared to 6Mdiet, the 3Meal diet timing schedule, was most effective in reducing body weight, HbA1c, overall hyperglycemia, and led to up-regulation of SIRT1 and Clock Genes mRNA expression in leukocytes. However, this effect of meal timing had never been explored in liver cells. The investigators hypothesized that compared to Allday Diet (6Mdiet), the serum collected from T2D participants following Breakfast Diet (3Mdiet) will up-regulate SIRT1 and Clock Genes oscillatory mRNA expression in cultured hepatocytes.
- Conditions
- Type 2 Diabetes, Obesity
- Being tested
- Breakfast Diet, Allday Diet
- Keywords
- Diabetes, Meal Timing, Clock Genes, Hepatocytes
- Medical subject headings
- Diabetes Mellitus, Type 2, Obesity, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Breakfast DietOther
Also called 3Mdiet
Breakfast Diet (3Mdiet) consist on high-energy breakfast and reduced in energy and carbohydrate (CH) dinner. Participants fasting serum to provide serum to for the in ex-vivo cell studies, will be collected at fasting (8:00), at start (day 0), after 2 weeks and at the end of 3Mdiet intervention (12 weeks). The participants serum is added to culture medium (as serum conditioned medium) to treat during 48 hours the cultured hepatocytes. After 48 hours of serum treatment, the mRNA extraction for the assessment of SIRT1 and Clock Gene expression will be performed at 00:00, 06:00, 12:00 and at 18:00 to assess SIRT1 and the Clock Genes circadian oscillation in hepatocytes. The 3Mdiet efficacy on reducing the overall glycemic excursions is assessed with continuous monitoring system at baseline after 2 weeks month of diet intervention.
Allday DietOther
Also called 6Mdiet
Allday Diet (6Mdiet) consist in 6 small meals: breakfast, lunch and dinner and 3 snacks, with calories and carbohydrates (CH) evenly distributed throughout the day. Participants fasting serum to provide serum to for the in ex-vivo cell studies, will be collected at fasting (8:00), at start (day 0), after 2 weeks and at the end of 6Mdiet intervention (12 weeks). The participants serum is added to culture medium (as serum conditioned medium) to treat during 48 hours the cultured hepatocytes. After 48 hours of serum treatment, the mRNA extraction for the assessment of SIRT1 and Clock Gene expression will be performed at 00:00, 06:00, 12:00 and at 18:00 to assess SIRT1 and the Clock Genes circadian oscillation in hepatocytes. The 6Mdiet efficacy on reducing the overall glycemic excursions is assessed with continuous monitoring system at baseline after 2 weeks month of diet intervention.
| Study group | Role | What they receive |
|---|---|---|
| Breakfast Diet (3Mdiet) | Experimental | The Breakfast Diet (3Mdiet) will consist in 3 meals with distribution of calories: breakfast 50%, lunch 33% and dinner 17%. Receives: Other: Breakfast Diet |
| Allday Diet (6Mdiet) | Active comparator | The Allday Diet (6Mdiet) will consist on 6 meals (breakfast, lunch and dinner and 3 snacks) with distribution of calories: breakfast 15%, lunch 25%, dinner 30% and 10% in each of the three snacks. Receives: Other: Allday Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Clock Genes mRNA
Change from baseline serum-induced hepatocyte Clock Gene mRNA expression, will be assessed at 2 weeks post diet intervention in the two groups:Breakfast Diet (3Mdiet) and Allday Diet (6Mdiet)
Measured: Baseline and at 2 weeks post diet intervention
Secondary outcomes (3)
Change in Clock Genes expression
Change from baseline serum-induced hepatocyte Clock Gene expression, will be assessed at 12 weeks post diet intervention in the two groups: Breakfast Diet (3Mdiet) and Allday Diet (6Mdiet)
Measured: Baseline and at 12 weeks post diet intervention
Change in SIRT1 mRNA expression
Change from baseline serum-induced hepatocyte SIRT1 mRNA expression, will be assessed at 2 weeks post diet intervention in the two groups: Breakfast Diet (3Mdiet) and Allday Diet (6Mdiet)
Measured: Baseline and at 2 weeks post diet intervention
Change in Overall Glycemia
Change from baseline in overall glycemia will be assessed at 12 weeks post diet intervention in the two groups: Breakfast Diet (3Mdiet) and Allday Diet (6Mdiet) Overall glycemia will be test by using continuous blood monitoring system
Measured: Baseline and at 12 weeks post diet intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2020
- Study start31 May 2020 (estimated)
- Primary completion20 Sep 2020 (estimated)
- Study completion20 Oct 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The researcher will explore the effect of serum samples collected from T2D participants following either Breakfast Diet (3Mdiet) or Allday Diet (6Mdiet) schedule, on SIRT1 and Clock Gene circadian expression of cultured hepatocytes using the ex-vivo/in-vitro approach
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tel Aviv University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniela Jakubowicz, Tel Aviv University
- Investigators
- Daniela Jakubowicz, MD, Principal investigator, Wolfson Medical CenterShani Tsameret, RD, Principal investigator, E. Wolfson Medical Center.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04405895
- Sponsor's protocol ID
- 0118-20-WOMC
- Acronym
- Liver-CG
- Status last verified
- May 2020
- First submitted
- 19 May 2020
- Last updated
- 28 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect Meal Timing in Type 2 Diabetes on Serum Induced SIRT1 and Clock Gene Expression in Hepatocytes
- ClinicalTrials.gov ID
- NCT04405895
- Acronym / sponsor ID
- Liver-CG / 0118-20-WOMC
- Conditions
- Type 2 Diabetes, Obesity
- Keywords
- Diabetes, Meal Timing, Clock Genes, Hepatocytes
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Tel Aviv UniversityUniversity, hospital or other
- Study start
- 31 May 2020 (estimated)
- Primary completion
- 20 Sep 2020 (estimated)
- Study completion
- 20 Oct 2020 (estimated)
- First posted
- 28 May 2020 (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 study is undertaken to explore in T2D, the effect of meal timing on serum induced SIRT1 and Clock Genes mRNA expression in cultured hepatocytes. Fasting serum samples were collected from T2D participants, following two different meal timing schedules, either a diet with large breakfast and lunch with small dinner Breakfast Diet (3Mdiet) or an isocaloric diet with 6 small meals evenly distributed along the day Allday Diet (6Mdiet). The researchers will use an ex-vivo/in-vitro approach in which cultured medium will be conditioned with the fasted human serum collected from the two groups of T2D participants at baseline, after 2 weeks and after 12 week of the diet intervention.
Detailed description
The timing of many physiological processes, including glucose metabolism, is coordinated by the circadian clock gene system. The circadian clock regulation, optimize glucose metabolism for the consumption of high energy and carbohydrate (CH) meals in the early hours of the day and for fasting at evening and night. Circadian disruption which occurs when the meal timing is not aligned with the circadian clock rhythms like skipping breakfast, overeating CH at night or eating CH all day, lead to desynchronized clock genes and can result in adverse health outcomes like insulin resistance, obesity hyperglycemia and T2D. Although the clock genes are disseminated in almost all peripheral tissues, those localized in the liver, are particularly important for the regulation of glucose metabolism, influencing the enzymatic determinants of the hepatic glucose output, by enhancing glycogen storage and suppressing nocturnal hepatic glucose production (glycogenolysis and gluconeogenesis sequentially).Therefore, the disruption of the hepatic clock genes lead to fasting, nocturnal, and to postprandial hyperglycemia in T2D. The researchers had previously shown in T2D, that compared to 6Mdiet, the 3Meal diet timing schedule, was most effective in reducing body weight, HbA1c, overall hyperglycemia, and led to up-regulation of SIRT1 and Clock Genes mRNA expression in leukocytes. However, this effect of meal timing had never been explored in liver cells. The investigators hypothesized that compared to Allday Diet (6Mdiet), the serum collected from T2D participants following Breakfast Diet (3Mdiet) will up-regulate SIRT1 and Clock Genes oscillatory mRNA expression in cultured hepatocytes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The researcher will explore the effect of serum samples collected from T2D participants following either Breakfast Diet (3Mdiet) or Allday Diet (6Mdiet) schedule, on SIRT1 and Clock Gene circadian expression of cultured hepatocytes using the ex-vivo/in-vitro approach
| Arm | Type | Receives |
|---|---|---|
| Breakfast Diet (3Mdiet) | Experimental | Other: Breakfast DietThe Breakfast Diet (3Mdiet) will consist in 3 meals with distribution of calories: breakfast 50%, lunch 33% and dinner 17%. |
| Allday Diet (6Mdiet) | Active comparator | Other: Allday DietThe Allday Diet (6Mdiet) will consist on 6 meals (breakfast, lunch and dinner and 3 snacks) with distribution of calories: breakfast 15%, lunch 25%, dinner 30% and 10% in each of the three snacks. |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- T2D patients with stable treatment for at least 3 month preceding the study.
- HgA1c >7.5 %.
- Age > 30 years.
- BMI: 27-34 kg/m2.
- Treatment with antidiabetic drugs (i.e. metformin, DPP4 inhibitors, glinides) and GLP-1 analogs, will be allowed
Key exclusion criteria (5 listed)
- Type 1 diabetes.
- Major illnesses (liver, heart, kidney, infectious, neurological, psychiatric, immunological, active malignancy).
- Change in weight of > 4.5 kg within 3 month prior the diet onset.
- Night or rotating shift workers.
- Those who crossed more than 2 time zones during 2-week period prior to study onset.
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 |
|---|---|---|
| Breakfast DietAlso: 3MdietBreakfast Diet (3Mdiet) consist on high-energy breakfast and reduced in energy and carbohydrate (CH) dinner. Participants fasting serum to provide serum to for the in ex-vivo cell studies, will be collected at fasting (8:00), at start (day 0), after 2 weeks and at the end of 3Mdiet intervention (12 weeks). The participants serum is added to culture medium (as serum conditioned medium) to treat during 48 hours the cultured hepatocytes. After 48 hours of serum treatment, the mRNA extraction for the assessment of SIRT1 and Clock Gene expression will be performed at 00:00, 06:00, 12:00 and at 18:00 to assess SIRT1 and the Clock Genes circadian oscillation in hepatocytes. The 3Mdiet efficacy on reducing the overall glycemic excursions is assessed with continuous monitoring system at baseline after 2 weeks month of diet intervention. | Other | Breakfast Diet (3Mdiet) |
| Allday DietAlso: 6MdietAllday Diet (6Mdiet) consist in 6 small meals: breakfast, lunch and dinner and 3 snacks, with calories and carbohydrates (CH) evenly distributed throughout the day. Participants fasting serum to provide serum to for the in ex-vivo cell studies, will be collected at fasting (8:00), at start (day 0), after 2 weeks and at the end of 6Mdiet intervention (12 weeks). The participants serum is added to culture medium (as serum conditioned medium) to treat during 48 hours the cultured hepatocytes. After 48 hours of serum treatment, the mRNA extraction for the assessment of SIRT1 and Clock Gene expression will be performed at 00:00, 06:00, 12:00 and at 18:00 to assess SIRT1 and the Clock Genes circadian oscillation in hepatocytes. The 6Mdiet efficacy on reducing the overall glycemic excursions is assessed with continuous monitoring system at baseline after 2 weeks month of diet intervention. | Other | Allday Diet (6Mdiet) |
Primary outcome
Change in Clock Genes mRNA
Time frame: Baseline and at 2 weeks post diet intervention
Change from baseline serum-induced hepatocyte Clock Gene mRNA expression, will be assessed at 2 weeks post diet intervention in the two groups:Breakfast Diet (3Mdiet) and Allday Diet (6Mdiet)
3 secondary outcomes
Change in Clock Genes expression
Time frame: Baseline and at 12 weeks post diet intervention
Change in SIRT1 mRNA expression
Time frame: Baseline and at 2 weeks post diet intervention
Change in Overall Glycemia
Time frame: Baseline and at 12 weeks post diet intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2020.
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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.
Daniela Jakubowicz, MD principal investigator
Wolfson Medical Center
Shani Tsameret, RD principal investigator
E. Wolfson Medical Center.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Breakfast Diet and Allday Diet in people with Type 2 Diabetes and Obesity, run by Tel Aviv University at 1 site in Israel.
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 7 inclusion and 5 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 28 May 2020. 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 Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Daniela Jakubowicz, MD (+972508105552, daniela.jak@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Clock Genes mRNA (time frame: Baseline and at 2 weeks post diet intervention). 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 28 May 2020.