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How Does Dietary Carbohydrate Influence the Formation of an Atherogenic Lipoprotein Phenotype (ALP)? (CHOT)

This study has been completed.
Sponsor:
Collaborators:
Imperial College London
University of Cambridge
Information provided by (Responsible Party):
Bruce A. Griffin, University Of Surrey
ClinicalTrials.gov Identifier:
NCT01790984
First received: February 11, 2013
Last updated: NA
Last verified: February 2013
History: No changes posted
  Purpose

The hypothesis of this study is that a diet high in sugars will increase abnormalities in blood lipids which are associated with increased cardiovascular disease risk, relative to a diet which is low in sugar. We predict that this potentially adverse effect of dietary sugars on blood lipids will be more pronounced in people with a raised level of stored fat inside their liver, as compared to people with a low level of stored fat.


Condition Intervention
Non-alcoholic Fatty Liver Disease
Other: High sugar low starch diet
Other: Low sugar high starch diet

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: How Does Dietary Carbohydrate Influence the Formation of an Atherogenic Lipoprotein Phenotype?

Resource links provided by NLM:


Further study details as provided by University of Surrey:

Primary Outcome Measures:
  • Plasma concentration of triglyceride (mmol/l) in the post-absorptive state (after 12 hour fast) [ Time Frame: Pre and post 12 week dietary intervention ] [ Designated as safety issue: No ]
    Total plasma triglyceride (TG) is a measure of the TG transported in the plasma by all the principal plasma lipoproteins, very low density (chiefly), intermediate density, low density and high density lipoproteins.

  • Very low density lipoprotein (VLDL) kinetics: Fractional catabolic and production rates of large and small VLDL glycerol (2H-5 deuterated glycerol) and apoprotein B (1-C-13 leucine). [ Time Frame: Post-(12 week) dietary interventions ] [ Designated as safety issue: No ]
    VLDL was labelled in vivo by the constant infusion of two stable isotopes (deuterated H5-glycerol and carbon 13 leucine). The labels are then isolated in large/light and small/dense fractions of VLDL, intermediate density lipoprotein (IDL) and large/light and small/dense low desnity lipoprotein (LDL) by sequential ultra-centrifugation, and detected by GC-MS as measures of lipoprotein (glycerol and apoprotein) kinetics in vivo. Lipoprotein kinetics are being described by mathematic models which are currently being developed at the University of Cambridge.

  • De novo lipogenesis (synthesis of liver fat) [ Time Frame: Post-dietary interventions -after 12 weeks x 2 ] [ Designated as safety issue: No ]
    Acetyl CoA is labelled in vivo by the consumption of deuterated (heavy) water and provides a measure of fatty acid and TG synthesis in the liver.

  • C-13 palmitate kinetics [ Time Frame: Post-dietary interventions - after 12 weeks x 2 ] [ Designated as safety issue: No ]
    Palmitate was labelled in vivo by the infusion of U-13 Carbon. This provides a measure of the rate of intra-cellular lipolysis and contribution of systemic palmitate to the synthesis of TG in the liver.


Secondary Outcome Measures:
  • Percentage of intra-hepatocellular lipid (IHCL) [ Time Frame: Pre and post-dietary intervetions x 4 measures ] [ Designated as safety issue: No ]
    Percentage of IHCL was measured by magnetic resonance spectroscopy.


Enrollment: 27
Study Start Date: April 2009
Study Completion Date: September 2012
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High sugar low starch diet
A high sugar, low starch diet was provided by the exchange of two thirds of the participants daily intake of carbohydrate. This was achieved by exchanging foods with low sugar to starch content, with foods containing a high sugar to starch content to reach a target ratio of starch to sugar of 1:1.2
Other: High sugar low starch diet Other: Low sugar high starch diet
Experimental: Low sugar high starch diet
A high sugar, low starch diet was provided by the exchange of two thirds of the participants daily intake of carbohydrate. This was achieved by exchanging foods with a high sugar to starch content, with foods containing a low sugar to starch content to reach a target ratio of starch to sugar of 5:1
Other: High sugar low starch diet Other: Low sugar high starch diet

Detailed Description:

This study aims to determine the metabolic mechanism(s) by which dietary extrinsic sugars (sucrose and fructose), promote the formation of a high risk dyslipidaemia, known as an atherogenic lipoprotein phenotype (raised plasma triglyceride, low HDL and predominance of small, dense LDL), in men with raised cardio-metabolic risk and percentage of liver fat, as determined by magnetic resonance spectroscopy (MRS). The study examined the impact of diets high and low in extrinsic sugars, on the metabolism of lipids and lipoproteins in vivo, of two groups of men with a high (>10%)and low (<2%)percentage of liver fat, by the trace-labelling of these lipid moieties with stable isotopes, and detection by gas chromatography mass spectrometry. The study had a two-way cross-over design, with two, 12 week dietary interventions separated by a six week wash-out period. The dietary intervention with high and low sugars was achieved by a dietary exchange with supermarket foods, which were consumed within the homes of the participants.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male gender,
  • Increased cardio-metabolic risk ('RISCK' criteria Jebb et al (2010) Am J Clin Nutr 92, 748-758).
  • Apo E3E3 genotype

Exclusion Criteria:

  • Any abnormal result in blood screen (renal and liver function, haematology)
  • Diabetes
  • Smoker
  • Excessive alcohol consumption (>27units/week)
  • Medication likely to affect lipid metabolism
  • >3kg weight loss in preceding 3 months
  • Any medical condition (eg. GI tract, allergies) affecting lipid metabolism or ability to comply with dietary interventions
  • Involvement in any other study
  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: NCT01790984

Locations
United Kingdom
University of Surrey
Guildford, Surrey, United Kingdom, GU2 7XH
Sponsors and Collaborators
Bruce A. Griffin
Imperial College London
University of Cambridge
Investigators
Principal Investigator: Bruce A Griffin, PhD University of Surrey
  More Information

No publications provided

Responsible Party: Bruce A. Griffin, Professor of Nutritional Metabolism, University Of Surrey
ClinicalTrials.gov Identifier: NCT01790984     History of Changes
Other Study ID Numbers: RN0172 A/B, BB/G009899/1
Study First Received: February 11, 2013
Last Updated: February 11, 2013
Health Authority: United Kingdom: Research Councils UK

Keywords provided by University of Surrey:
Dietary extrinsic sugars, atherogenic lipoprotein phenotype, lipoprotein kinetics, fatty liver

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on October 23, 2014