Fructose Consumption and Metabolic Dysregulation

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2011 by Helsinki University Central Hospital
Sponsor:
Collaborators:
Sahlgrenska University Hospital, Sweden
Lund University
University of Naples
Laval University
Information provided by (Responsible Party):
Marja-Riitta Taskinen, Helsinki University Central Hospital
ClinicalTrials.gov Identifier:
NCT01445730
First received: September 28, 2011
Last updated: October 4, 2011
Last verified: October 2011
  Purpose

High fructose intake is increasingly recognized as causative in development of prediabetes, metabolic syndrome and cardiovascular disease (CVD). The mechanisms underlying fructose-induced metabolic disturbances are unclear but are beginning to be unraveled. In contrast to metabolism of glucose, the breakdown of fructose leads to the generation of metabolites that stimulate hepatic de novo lipogenesis (DNL) and increased levels of both fasting and postprandial triglycerides. The key lipogenic transcription factor seems to be activated by fructose independently of insulin. However, it is still controversial whether fructose consumption increases DNL in man to the extent that it induces metabolic disturbances. Animal studies have shown that also the adipose tissue is responsive to fructose feeding fructose, and that high fructose-feeding induces insulin resistance and inflammation in the adipose tissue. The role of intestinal insulin resistance in fructose-induced dysmetabolism has not been studied in detail. The critical question is whether the metabolic disturbances are induced by calorie excess or by fructose per se.


Condition Intervention
Central Obesity
Hypertriglyceridemia
Dietary Supplement: Fructose

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Fructose Consumption Aggravates Dysregulation of Postprandial Lipid Metabolism in Obese Hypertriglyceridemic Men With High Cardiometabolic Risk Profile and Associates With Liver Fat Deposition

Resource links provided by NLM:


Further study details as provided by Helsinki University Central Hospital:

Primary Outcome Measures:
  • Plasma Triglyceride (TG) area under curve (AUC) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Before vs. after fructose challenge: Postprandial plasma TG summary measure expressed as AUC (baseline to 8hours) after oral fat.

  • Very low density lipoprotein 1 (VLDL1) apolipoprotein B-100 (ApoB-100) kinetics [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Before vs. after fructose challenge: VLDL1 ApoB-100 secretion rate.

  • VLDL1 ApoB-100 kinetics [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    VLDL1 ApoB-100 catabolic rate


Secondary Outcome Measures:
  • Metabolic parameters [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Before vs. after fructose challenge: Postprandial lipids and apolipoproteins (8hours) after oral fat and/or non-steady state kinetic parameters

  • Metabolic parameters [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Before vs. after fructose challenge: Hepatic DNL

  • Metabolic parameters [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Before vs. after fructose challenge: Plasma inflammatory markers

  • Metabolic parameters [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Before vs. after fructose challenge: Incretin response

  • Metabolic parameters [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Before vs. after fructose challenge: Plasma and adipose tissue lipidomics /genetics.

  • Metabolic parameters [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Before vs. after fructose challenge: Gut microbiota profiling.


Estimated Enrollment: 128
Study Start Date: August 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hypercaloric fructose diet
1. TG ≤1.7 mmo/l 2. TG > 1.7 mmol/l
Dietary Supplement: Fructose
fructose drink 75 g/day per day while consuming a self-selected ad libitum diet
Active Comparator: Isocaloric fructose diet
3. TG ≤1.7 mmo/l 4. TG > 1.7 mmol/l
Dietary Supplement: Fructose
3 month fructose diet 75 g/day while consuming isocaloric diet

Detailed Description:

Detailed description: Study subjects will participate to studies 1-4 before and 3 m after fructose diet:

  1. An oral fat load or a kinetic study with stable isotopes combined with an oral fat load.
  2. Determination of liver, subcutaneous and intra-abdominal fat. (Proton magnetic resonance spectroscopy )
  3. Lipolytic enzymes, advanced lipid analysis, fat biopsies and genetic studies and gut microbiota profiling
  4. Oral glucose tolerance test and analysis of incretins and inflammatory biomarkers.
  Eligibility

Ages Eligible for Study:   20 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Body mass index 27-40
  • Waist > 96 cm
  • Age 20-60 years
  • Male

Exclusion Criteria:

  • Smoking
  • Active health problems
  • Contraindications to MRI scanning
  • Bleeding tendency
  • Abnormal liver or renal function tests
  • Type 2 diabetes
  • Evidence of metabolic or viral liver disease
  • Alcohol intake > 21 units per week
  • Chronic medication except ones needed for stable hypertension
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01445730

Contacts
Contact: Niina Matikainen, MD, PhD +358-94711

Locations
Canada
Université Laval Recruiting
Québec, Canada
Contact: Jean-Pierre Despres, Professor         
Finland
Helsinki University Central Hospital, Biomedicum Recruiting
Helsinki, Finland, 00290
Italy
University of Naples, Federico II, and Faculty of Medicine Not yet recruiting
Naples, Italy
Contact: Angela A Rivellese, Professor         
Sweden
Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital Recruiting
Gothenburg, Sweden
Contact: Björn Eliasson, Adjunct prof         
Sponsors and Collaborators
Marja-Riitta Taskinen
Sahlgrenska University Hospital, Sweden
Lund University
University of Naples
Laval University
Investigators
Principal Investigator: Marja-Riitta Taskinen, Professor Helsinki University Central Hospital, Biomedicum
  More Information

No publications provided

Responsible Party: Marja-Riitta Taskinen, Professor, Helsinki University Central Hospital
ClinicalTrials.gov Identifier: NCT01445730     History of Changes
Other Study ID Numbers: T1010K0029
Study First Received: September 28, 2011
Last Updated: October 4, 2011
Health Authority: Finland: Ethics Committee

Keywords provided by Helsinki University Central Hospital:
fructose
hypertriglyceridemia
postprandial lipids
de novo lipogenesis
stable isotopes

Additional relevant MeSH terms:
Hypertriglyceridemia
Obesity, Abdominal
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Nutrition Disorders
Obesity
Overnutrition

ClinicalTrials.gov processed this record on October 20, 2014