DGENES: Impact of a Short-Term High Fat or Low Fat Diet on Intestinal Genes Expression Involved in the Cholesterol and Fatty Acid Metabolism

Sponsor

Laval University (Other)

Overall Status

Completed

CT.gov ID

NCT01806441

Collaborator

(none)

Enrollment

Location

Arms

21.9

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Dietary fat has been shown to modulate cholesterol and fatty acids homeostasis and several lines of evidence suggest that this effect is associated with changes in the regulation of different genes at the intestine level involved in the cholesterol and fatty acid metabolism pathways. The present study will examine the impact of a short-term high fat diet versus a short-term low fat diet on expression of Niemann-Pick C1-like 1 (NPC1L1), adenosine triphosphate (ATP) binding cassette transporters (ABCG5/8), microsomal triglyceride transfer protein (MTP) and fatty acid transport protein-4 (FATP4), which have been shown to play a critical role in intestinal cholesterol absorption, chylomicron synthesis and dietary lipid absorption. Gene expression studies will be performed on duodenal biopsies. The primary hypothesis is that a short-term high fat diet will significantly decrease duodenal messenger ribonucleic acid (mRNA) levels of NPC1L1, ABCG5/8, MTP and FATP4 as compared with a short-term low fat diet.

Condition or Disease	Intervention/Treatment	Phase
Gene Expression	Other: 3-days high fat diet Other: 3-days low fat diet	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Impact of a Short-Term High Fat Diet Versus A Short-Term Low Fat Diet on Expression of the Key Intestinal Genes Involved in the Cholesterol and Fatty Acid Metabolism Pathways

Study Start Date :

Feb 1, 2009

Actual Primary Completion Date :

May 1, 2009

Actual Study Completion Date :

Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 3-days high fat diet During 3 days, subjects eat a diet high in fat (percent of total caloric intake: 15.0% from proteins; 49,8% from carbohydrates; 37.0% from fat).	Other: 3-days high fat diet During 3 days, subjects eat a diet high in fat (percent of total caloric intake: 15.0% from proteins; 49,8% from carbohydrates; 37.0% from fat).
Active Comparator: 3-days low fat diet During 3 days, subjects eat a diet low in fat (percent of caloric intake: 15.0% from proteins; 61,8% from carbohydrates; 25.0% from fats).	Other: 3-days low fat diet During 3 days, subjects eat a diet low in fat (percent of caloric intake: 15.0% from proteins; 61,8% from carbohydrates; 25.0% from fats).

Arm

Intervention/Treatment

Experimental: 3-days high fat diet

During 3 days, subjects eat a diet high in fat (percent of total caloric intake: 15.0% from proteins; 49,8% from carbohydrates; 37.0% from fat).

Other: 3-days high fat diet

During 3 days, subjects eat a diet high in fat (percent of total caloric intake: 15.0% from proteins; 49,8% from carbohydrates; 37.0% from fat).

Active Comparator: 3-days low fat diet

During 3 days, subjects eat a diet low in fat (percent of caloric intake: 15.0% from proteins; 61,8% from carbohydrates; 25.0% from fats).

Other: 3-days low fat diet

During 3 days, subjects eat a diet low in fat (percent of caloric intake: 15.0% from proteins; 61,8% from carbohydrates; 25.0% from fats).

Outcome Measures

Primary Outcome Measures

Change in duodenal mRNA expression of NPC1L1, ABCG5/8, MTP and FATP4. [At the end of the two 3-days diets (day 3 and day 17).]
Six biopsies (3 X 3 mm) will be obtained from the second portion of the duodenum during gastro-duodenoscopy. Biopsy specimen will be stored at -86°C before mRNA extraction. Total RNA will be isolated and used for polymerase chain reaction (PCR) quantification.

Secondary Outcome Measures

Change in surrogate markers of cholesterol absorption and synthesis. [At the end of the two 3-days diets (day 3 and day 17).]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Males 18 to 50 years of age
Non-smoker
Body mass index between 20.0 and 30.0 kg/m2
Plasma LDL-cholesterol levels between the 25th and 75th percentile for their age at day -14
Plasma triglyceride levels < 1.7 mmol/L (150 mg/dl) at day -14
Plasma HDL-cholesterol levels between 0.9 (35 mg/dl) and 1.6 mmol/L (60 mg/dl) at day -14
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 elevations in hepatic transaminases or creatine kinase (CK) or 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.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institute of nutrition and functional food	Quebec city	Quebec	Canada	G1V 0A6

Sponsors and Collaborators

Laval University

Investigators

Principal Investigator: Patrick Couture, MD,FRCP,PhD, Laval University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Patrick Couture, MD, FRCP, PhD, Laval University

ClinicalTrials.gov Identifier:

NCT01806441

Other Study ID Numbers:

INAF-125-05-06

First Posted:

Mar 7, 2013

Last Update Posted:

Mar 7, 2013

Last Verified:

Mar 1, 2013

Study Results

No Results Posted as of Mar 7, 2013