- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04260542
De Novo Lipogenesis and Insulin Sensitivity in Obese (DELISA)
February 14, 2023 updated by: Michaela Siklova, Charles University, Czech Republic
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
66
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Prague, Czechia
- Faculty Hospital Kralovske Vinohrady
-
Prague, Czechia, 100 00
- Charles University
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
25 years to 45 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
Female
Description
Inclusion Criteria:
- 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)
Exclusion Criteria:
- diagnosed cancer
- diabetes (T1DM and T2DM)
- liver and renal diseases
- major cardiovascular event
- bariatric surgery
- allergy to lidocaine
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: FAST Lean
Short-term fasting (FAST), comparator group of lean subjects
|
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).
Other Names:
|
Experimental: FAST Obese
Short-term fasting (FAST), experimental group of obese subjects
|
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).
Other Names:
|
Experimental: KETO Obese
Medium-term ketogenic diet intervention (KETO), experimental group of obese subjects
|
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).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Insulin sensitivity
Time Frame: through study completion, an average of 1 year
|
Change in insulin sensitivity index (ΔiAUC insulin/ΔiAUC glucose from OGTT)
|
through study completion, an average of 1 year
|
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)
|
through study completion, an average of 1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
gene expression profiling of adipose tissue
Time Frame: through study completion, an average of 1 year
|
Change in long non-coding RNA analysis by microarrays (ΔCT)
|
through study completion, an average of 1 year
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Exploratory outcome into adipose tissue lipolysis
Time Frame: through study completion, an average of 1 year
|
Change in glycerol, FFA concentration in AT explants
|
through study completion, an average of 1 year
|
Exploratory outcome into liver lipogenesis
Time Frame: through study completion, an average of 1 year
|
Change in amount of liver fat and VLDL-TG composition
|
through study completion, an average of 1 year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 1, 2019
Primary Completion (Actual)
March 11, 2022
Study Completion (Actual)
March 11, 2022
Study Registration Dates
First Submitted
January 23, 2020
First Submitted That Met QC Criteria
February 6, 2020
First Posted (Actual)
February 7, 2020
Study Record Updates
Last Update Posted (Actual)
February 15, 2023
Last Update Submitted That Met QC Criteria
February 14, 2023
Last Verified
February 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NV19-01-00263
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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