- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05965973
Diet Impact on Hepatic Transcriptomics and Lipidomics in Pre-diabetes (DGENE-NAFLD)
July 20, 2023 updated by: Patrick Couture, Laval University
Short-term Impact of a Low Carbohydrate/High Unsaturated Fat Diet on Hepatic Transcriptomics and Lipidomics in Individuals With Pre-diabetes - A Pilot Study
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, affecting 25% to 30% of the global population and nearly one third of the population in North America.
NAFLD is defined as an excessive accumulation of lipids within hepatocytes in the absence of significant alcohol consumption or other causes of chronic liver disease.
These patients usually present with hepatic steatosis observed on imaging studies and elevated liver enzymes with clinical features of insulin resistance (IR), including pre-diabetes, type 2 diabetes mellitus (T2DM), arterial hypertension, dyslipidemia, and visceral obesity.
The minimum criterion for a histologic diagnosis of NAFLD is >5 percent steatotic hepatocytes in a liver tissue section.
The exact mechanism for the development of NAFLD is unclear, although the current evidence indicates that it is likely a complex interplay among neurohormones, intestinal dysbiosis, nutrition, and genetics.
IR plays a crucial role in NAFLD pathophysiology mainly by increasing adipocyte lipolysis, resulting in the circulation of more free fatty acids available for hepatic uptake and increasing hepatic de novo lipogenesis.
There is yet no approved pharmacologic option for the treatment of NAFLD.
Current international guidelines on NAFLD emphasize the importance of lifestyle modifications for all patients with NAFLD and recommend 7-10% of weight loss and a "healthy diet", without suggesting any particular diet.
Recent data provide some support for the beneficial role of low carbohydrate (CHO)/high unsaturated fatty acid (both monounsaturated (MUFAs) and polyunsaturated (PUFAs)) dietary patterns for decreasing hepatic steatosis.
This proposal addresses this important research gap by leading to advances regarding the impact of a short-term low CHO/high PUFAs/MUFAs dietary intervention on improving hepatic gene expression profiles and lipid composition in individuals with pre-diabetes.
The proposed study is unique because all meals and foods will be provided to participants under carefully controlled isocaloric conditions to maintain a constant bodyweight with optimal energy and macronutrient intake control.
The primary objective of the proposed research is to investigate how replacement of dietary CHOs by unsaturated fatty acids (both PUFAs and MUFAs) affects liver fat composition and liver transcriptomics in subjects with pre-diabetes.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Estimated)
6
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 Contact
- Name: André Tremblay, PhD
- Phone Number: 411417 418-656-2131
- Email: andre.tremblay@fsaa.ulaval.ca
Study Contact Backup
- Name: Patrick Couture, MD, PhD
- Phone Number: 418-654-2106
- Email: patrick.couture@fmed.ulaval.ca
Study Locations
-
-
Quebec
-
Québec, Quebec, Canada, G1V 0A6
- Recruiting
- Institute of Nutrition and Functional Foods (INAF)
-
Contact:
- André Tremblay, PhD
- Phone Number: 411417 418-656-2131
- Email: andre.tremblay@fsaa.ulaval.ca
-
Contact:
- Patrick Couture, MD, PhD
- Phone Number: 418-654-2106
- Email: patrick.couture@fmed.ulaval.ca
-
Principal Investigator:
- Patrick Couture, MD, PhD
-
-
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
- Adult
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Males and females 18 to 60 years of age.
- Non-smoker
- Waist circumference > 102 cm for men and > 88 cm for women.
- Plasma triglyceride levels > 1,7 mmol/L at the screening visit.
- Fasting plasma glucose levels > 6,1 mmol/L at the screening visit.
- Fasting plasma insulin levels above the upper limit of normal at the screening visit.
- Subjects must be willing to give written informed consent and able to adhere to the diet schedule and visit schedule.
- Patients should be otherwise healthy, without abnormal renal function or coagulation.
Exclusion Criteria:
- Patients with extreme dyslipidemias, such as familial hypercholesterolemia will be excluded.
- Subjects will be excluded if they have cardiovascular disease (CHD, cerebrovascular disease or peripheral arterial disease) or if they are taking other medications known to affect lipoprotein metabolism (eg. steroids, beta blockers, thiazide diuretics, other lipid lowering agents, significant alcohol intake etc.).
- Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study.
- Individuals with a history of mental instability, drug or alcohol abuse within the past 2 years or individuals who have been treated or are being treated for severe psychiatric illness that, in the opinion of the investigator, may interfere with optimal participation in the study.
- Disorders of the hematologic, digestive, or central nervous systems, including cerebrovascular disease and degenerative disease, that would limit study evaluation or participation.
- Known impairment of renal function (creatinine >2.0 mg/dL), dysproteinemia, nephrotic syndrome, or other renal disease.
- Subjects with coagulopathy (prothrombin time [PT] or partial thromboplastin time [PTT] at Visit 1 higher than 1.5 times control).
- Patients who are known to have tested positive for human immunodeficiency virus (HIV).
- Patients who have used any investigational drug within 30 days of the first clinic visit.
- Diabetic patients are excluded from the study. Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins. Clinically euthyroid subjects on replacement doses of thyroid hormone are eligible for enrollment.
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: Prevention
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Low fat diet
During 3 days, subjects eat a diet low in fat (percent of total caloric intake: 15.0% from proteins; 65.0% from carbohydrates; 20.0% from fat: 4.0% from saturated fat; 10.0% from monounsaturated fat; 6.0% from polyunsaturated fat
|
During 3 days, subjects eat a diet low in fat (percent of total caloric intake: 15.0% from proteins; 65.0% from carbohydrates; 20.0% from fat: 4.0% from saturated fat; 10.0% from monounsaturated fat; 6.0% from polyunsaturated fat
During 3 days, subjects eat a diet high in fat (percent of total caloric intake: 15.0% from proteins; 45.0% from carbohydrates; 40.0% from fat: 8.0% from saturated fat; 22.0% from monounsaturated fat; 10.0% from polyunsaturated fat
|
Experimental: High fat diet
During 3 days, subjects eat a diet high in fat (percent of total caloric intake: 15.0% from proteins; 45.0% from carbohydrates; 40.0% from fat: 8.0% from saturated fat; 22.0% from monounsaturated fat; 10.0% from polyunsaturated fat
|
During 3 days, subjects eat a diet low in fat (percent of total caloric intake: 15.0% from proteins; 65.0% from carbohydrates; 20.0% from fat: 4.0% from saturated fat; 10.0% from monounsaturated fat; 6.0% from polyunsaturated fat
During 3 days, subjects eat a diet high in fat (percent of total caloric intake: 15.0% from proteins; 45.0% from carbohydrates; 40.0% from fat: 8.0% from saturated fat; 22.0% from monounsaturated fat; 10.0% from polyunsaturated fat
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in the expression of key genes in lipid metabolism including LDL-receptor, acetyl-CoA acetyltransferase 2, apolipoprotein B, proproprotein convertase subtilisin/kexin type 9, microsomal triglyceride transfer protein
Time Frame: At Day 3 and day 20 (at the end of the two 3-day diets)
|
At Day 3 and day 20 (at the end of the two 3-day diets)
|
Change in the expression of key genes in liver inflammation including C-reactive protein, Interleukin-6, Interleukin-15, cell adhesion molecules, E-selectin
Time Frame: At Day 3 and day 20 (at the end of the two 3-day diets)
|
At Day 3 and day 20 (at the end of the two 3-day diets)
|
Change in the expression of key genes in hepatic fibrogenesis including transforming growth factor beta 1, a-smooth muscle actin, type-1 collagen, connective tissue growth factor
Time Frame: At Day 3 and day 20 (at the end of the two 3-day diets)
|
At Day 3 and day 20 (at the end of the two 3-day diets)
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in liver's key lipid pathways (lipidomics) including lysophosphatidylcholine, phosphatidylcholine, diglyceride.
Time Frame: At Day 3 and day 20 (at the end of the two 3-day diets)
|
At Day 3 and day 20 (at the end of the two 3-day diets)
|
Identify bacteria strains involved in the control of blood glucose such as C elegans.
Time Frame: At Day 3 and day 20 (at the end of the two 3-day diets)
|
At Day 3 and day 20 (at the end of the two 3-day diets)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Patrick Couture, MD, PhD, Laval University
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)
June 9, 2023
Primary Completion (Estimated)
March 31, 2024
Study Completion (Estimated)
December 31, 2024
Study Registration Dates
First Submitted
June 12, 2023
First Submitted That Met QC Criteria
July 20, 2023
First Posted (Actual)
July 28, 2023
Study Record Updates
Last Update Posted (Actual)
July 28, 2023
Last Update Submitted That Met QC Criteria
July 20, 2023
Last Verified
July 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- INAF 2023-6814
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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