Insulin ResistanceDELISANCT04260542
De Novo Lipogenesis and Insulin Sensitivity in Obese
A study testing Fasting/refeeding and Ketogenic diet/ fasting in people with Insulin Resistance and Obesity, run by Charles University, Czech Republic at 2 sites in Czechia.
Trial summary
Disturbances of de novo lipogenesis (DNL) are one of the features of dysfunction of adipose tissue (AT). Disturbances of DNL play a role in development of metabolic complications of obesity. The goal of this project is to investigate novel pathways of DNL regulation. Read more about this study
- Who is it for?
- Ages 25 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance, Obesity
- What is being tested?
- Fasting/refeeding and Ketogenic diet/ fasting
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 2 sitesCzechia
- Study dates
- 1 May 2019to 11 Mar 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 25 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- sedentary premenopausal women
- lean (n=20-25, age 25-40 years, BMI 20-25 kg/m2)
- obese (n=20-25, age 25-40 years, BMI 30-40 kg/m)
Who cannot join
- diagnosed cancer
- diabetes (T1DM and T2DM)
- liver and renal diseases
- major cardiovascular event
- bariatric surgery
- allergy to lidocaine
Show all 14Show fewer
- positive serology for hepatitis (B and C) and HIV
- smoking above 10 cigarettes/day, alcohol consumption above 66g/day
- sleep apnea
- poor venous status
- weight-change more than 3kg in last 3 months
- untreated hyper- or hypo-thyroidism
- long term use of medication and/or steroids
- shift workers and individuals with abnormal sleep/wake pattern
Trial locations and contacts
2 sites in 1 country.
Czechia2 sites
Charles University
Prague, 100 00
Faculty Hospital Kralovske Vinohrady
Prague
About this study
Official title: The Role of De Novo Lipogenesis in Regulation of Insulin Sensitivity in Adipose Tissue in Obese
Disturbances of de novo lipogenesis (DNL) are one of the features of dysfunction of adipose tissue (AT). Disturbances of DNL play a role in development of metabolic complications of obesity. The goal of this project is to investigate novel pathways of DNL regulation. DNL will be studied during nutritional interventions in healthy and obese subjects in exposure to 2-days high carbohydrate diet preceded by a) 2-days fasting b) several weeks´ ketogenic diet. This nutritional protocol creates conditions for the study of prominent changes in DNL: suppression of DNL during fasting or ketogenic diet followed by stimulation during high-carbohydrate diet. Systemic phenotypic features and molecular indices of DNL regulation in AT will be followed during the protocols. Specific attention will be paid to newly reported pathway- hormone sensitive lipase and transcription factor ChREBP. The results will contribute to development of pharmacological approaches in the treatment of metabolic complications of obesity, targeted selectively to AT, without side effects in other tissues.
Read the detailed description
The main goal of the proposed project is to characterize the regulation of de novo lipogenesis in AT, a pathway strongly associated with insulin sensitivity in humans. The project should provide information that will bring proof-of-concept for the development of AT DNL-targeting therapeutic strategies to decrease the metabolic risk in obese individuals. Two protocols in lean and obese women to modulate (inhibit/induce) DNL will be implemented: 1) two days of fasting followed by two days of high-carbohydrate diet refeeding (FAST/RF) in lean and obese women; 2) "fasting-mimicking" intervention in obese women with high fat low carbohydrate ketogenic diet followed by two days of high-carbohydrate diet refeeding (KETO/RF). KETO diet should provide long lasting AT DNL inhibition, and as such it should further highlight the processes necessary for DNL activation in the refeeding phase. The unique protocols proposed in the application will allow to investigate in humans the relationship between AT DNL and whole body insulin sensitivity and glucose tolerance. Moreover, the state of the art experimental methodologies applied for the analyses of AT samples should uncover the possible mechanisms of regulation of DNL by ChREBP, HSL and other factors as well as the related AT secretory capacity in humans. The findings obtained in lean subjects will be compared to obese subjects, as the deregulated response of these pathways might be expected. The project will provide a proof-of-principle for the role of AT DNL in the regulation of insulin sensitivity in lean and obese individuals. The results will indicate novel pathways for future development of drugs targeting the relevant sites in AT in the context of treatment of obesity-induced insulin resistance and associated disorders.
- Conditions
- Insulin Resistance, Obesity
- Being tested
- Fasting/refeeding, Ketogenic diet/ fasting
- Keywords
- adipose tissue, insulin resistance, obesity, ketogenic diet, de novo lipogenesis
- Medical subject headings
- Insulin Resistance, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fasting/refeedingBehavioural
Also called FAST lean
2-days fasting followed by 2-days of refeeding. During the fasting period the subjects will be hospitalized to control their state of health and ensure fasting compliance. During refeeding the standardized meals will be provided to cover individual daily requirements (60% carbohydrates, 15% protein, 25 % fat).
Fasting/refeedingBehavioural
Also called FAST obese
2-days fasting followed by 2-days of refeeding. During the fasting period the subjects will be hospitalized to control their state of health and ensure fasting compliance. During refeeding the standardized meals will be provided to cover individual daily requirements (60% carbohydrates, 15% protein, 25 % fat).
Ketogenic diet/ fastingBehavioural
Also called KETO obese
1 month of fasting-mimicking ketogenic diet and subsequent 2-days of refeeding. The subjects will be instructed by nutritional specialist to follow isocaloric ketogenic diet consisting of 6% carbohydrates, 17 % of proteins and 77% fat to cover individual energy demand. During refeeding the standardized meals will be provided to cover individual daily requirements (60% carbohydrates, 15% protein, 25 % fat).
| Study group | Role | What they receive |
|---|---|---|
| FAST Lean | Active comparator | Short-term fasting (FAST), comparator group of lean subjects Receives: Behavioral: Fasting/refeeding |
| FAST Obese | Experimental | Short-term fasting (FAST), experimental group of obese subjects Receives: Behavioral: Fasting/refeeding |
| KETO Obese | Experimental | Medium-term ketogenic diet intervention (KETO), experimental group of obese subjects Receives: Behavioral: Ketogenic diet/ fasting |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin sensitivity
Change in insulin sensitivity index (ΔiAUC insulin/ΔiAUC glucose from OGTT)
Measured: through study completion, an average of 1 year
De Novo Lipogenesis in adipose tissue
Change in mRNA expression of lipogenic genes and by targeted and non-targeted lipid analysis (ΔCT)
Measured: through study completion, an average of 1 year
Secondary outcomes (1)
gene expression profiling of adipose tissue
Change in long non-coding RNA analysis by microarrays (ΔCT)
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2020
- Study start1 May 2019
- Primary completion11 Mar 2022
- Study completion11 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- More trials run by Charles University, Czech RepublicThe 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Charles University, Czech Republic
- Sponsor type
- University, hospital or other
- Collaborators
- Faculty Hospital Kralovske Vinohrady, Institut National de la Santé Et de la Recherche Médicale, France
- Responsible party
- Principal investigator, Michaela Siklova, Charles University, Czech Republic
- Investigators
- Michaela Siklova, PhD, Principal investigator, Charles University, Czech Republic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04260542
- Sponsor's protocol ID
- NV19-01-00263
- Acronym
- DELISA
- Status last verified
- Feb 2023
- First submitted
- 23 Jan 2020
- Last updated
- 15 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of De Novo Lipogenesis in Regulation of Insulin Sensitivity in Adipose Tissue in Obese
- ClinicalTrials.gov ID
- NCT04260542
- Acronym / sponsor ID
- DELISA / NV19-01-00263
- Conditions
- Insulin Resistance, Obesity
- Keywords
- adipose tissue, insulin resistance, obesity, ketogenic diet, de novo lipogenesis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Charles University, Czech RepublicUniversity, hospital or other
- Collaborators
- Faculty Hospital Kralovske Vinohrady, Institut National de la Santé Et de la Recherche Médicale, France
- Study start
- 1 May 2019 (actual)
- Primary completion
- 11 Mar 2022 (actual)
- Study completion
- 11 Mar 2022 (actual)
- First posted
- 7 Feb 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.
Disturbances of de novo lipogenesis (DNL) are one of the features of dysfunction of adipose tissue (AT). Disturbances of DNL play a role in development of metabolic complications of obesity. The goal of this project is to investigate novel pathways of DNL regulation. DNL will be studied during nutritional interventions in healthy and obese subjects in exposure to 2-days high carbohydrate diet preceded by a) 2-days fasting b) several weeks´ ketogenic diet. This nutritional protocol creates conditions for the study of prominent changes in DNL: suppression of DNL during fasting or ketogenic diet followed by stimulation during high-carbohydrate diet. Systemic phenotypic features and molecular indices of DNL regulation in AT will be followed during the protocols. Specific attention will be paid to newly reported pathway- hormone sensitive lipase and transcription factor ChREBP. The results will contribute to development of pharmacological approaches in the treatment of metabolic complications of obesity, targeted selectively to AT, without side effects in other tissues.
Detailed description
The main goal of the proposed project is to characterize the regulation of de novo lipogenesis in AT, a pathway strongly associated with insulin sensitivity in humans. The project should provide information that will bring proof-of-concept for the development of AT DNL-targeting therapeutic strategies to decrease the metabolic risk in obese individuals. Two protocols in lean and obese women to modulate (inhibit/induce) DNL will be implemented: 1) two days of fasting followed by two days of high-carbohydrate diet refeeding (FAST/RF) in lean and obese women; 2) "fasting-mimicking" intervention in obese women with high fat low carbohydrate ketogenic diet followed by two days of high-carbohydrate diet refeeding (KETO/RF). KETO diet should provide long lasting AT DNL inhibition, and as such it should further highlight the processes necessary for DNL activation in the refeeding phase. The unique protocols proposed in the application will allow to investigate in humans the relationship between AT DNL and whole body insulin sensitivity and glucose tolerance. Moreover, the state of the art experimental methodologies applied for the analyses of AT samples should uncover the possible mechanisms of regulation of DNL by ChREBP, HSL and other factors as well as the related AT secretory capacity in humans. The findings obtained in lean subjects will be compared to obese subjects, as the deregulated response of these pathways might be expected. The project will provide a proof-of-principle for the role of AT DNL in the regulation of insulin sensitivity in lean and obese individuals. The results will indicate novel pathways for future development of drugs targeting the relevant sites in AT in the context of treatment of obesity-induced insulin resistance and associated disorders.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| FAST Lean | Active comparator | Behavioral: Fasting/refeedingShort-term fasting (FAST), comparator group of lean subjects |
| FAST Obese | Experimental | Behavioral: Fasting/refeedingShort-term fasting (FAST), experimental group of obese subjects |
| KETO Obese | Experimental | Behavioral: Ketogenic diet/ fastingMedium-term ketogenic diet intervention (KETO), experimental group of obese subjects |
Who may qualify
- Ages
- 25 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- sedentary premenopausal women
- lean (n=20-25, age 25-40 years, BMI 20-25 kg/m2)
- obese (n=20-25, age 25-40 years, BMI 30-40 kg/m)
Key exclusion criteria (14 listed)
- diagnosed cancer
- diabetes (T1DM and T2DM)
- liver and renal diseases
- major cardiovascular event
- bariatric surgery
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 |
|---|---|---|
| Fasting/refeedingAlso: FAST lean2-days fasting followed by 2-days of refeeding. During the fasting period the subjects will be hospitalized to control their state of health and ensure fasting compliance. During refeeding the standardized meals will be provided to cover individual daily requirements (60% carbohydrates, 15% protein, 25 % fat). | Behavioural | FAST Lean |
| Fasting/refeedingAlso: FAST obese2-days fasting followed by 2-days of refeeding. During the fasting period the subjects will be hospitalized to control their state of health and ensure fasting compliance. During refeeding the standardized meals will be provided to cover individual daily requirements (60% carbohydrates, 15% protein, 25 % fat). | Behavioural | FAST Obese |
| Ketogenic diet/ fastingAlso: KETO obese1 month of fasting-mimicking ketogenic diet and subsequent 2-days of refeeding. The subjects will be instructed by nutritional specialist to follow isocaloric ketogenic diet consisting of 6% carbohydrates, 17 % of proteins and 77% fat to cover individual energy demand. During refeeding the standardized meals will be provided to cover individual daily requirements (60% carbohydrates, 15% protein, 25 % fat). | Behavioural | KETO Obese |
Primary outcome
Insulin sensitivity
Time frame: through study completion, an average of 1 year
Change in insulin sensitivity index (ΔiAUC insulin/ΔiAUC glucose from OGTT)
De Novo Lipogenesis in adipose tissue
Time frame: through study completion, an average of 1 year
Change in mRNA expression of lipogenic genes and by targeted and non-targeted lipid analysis (ΔCT)
1 secondary outcome
gene expression profiling of adipose tissue
Time frame: through study completion, an average of 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2023.
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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.
Michaela Siklova, PhD principal investigator
Charles University, Czech Republic
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fasting/refeeding and Ketogenic diet/ fasting in people with Insulin Resistance and Obesity, run by Charles University, Czech Republic at 2 sites in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 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: finished, as of the sponsor's last update on 15 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Czechia. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Insulin sensitivity (time frame: through study completion, an average of 1 year). The study lists 2 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 15 Feb 2023.