Non-alcoholic Fatty Liver Disease (NAFLD)CHOTNCT01790984
How Does Dietary Carbohydrate Influence the Formation of an Atherogenic Lipoprotein Phenotype (ALP)?
A study testing High sugar low starch diet and Low sugar high starch diet in people with Non-alcoholic Fatty Liver Disease (NAFLD), run by Bruce A. Griffin at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease (NAFLD)
- What is being tested?
- High sugar low starch diet and Low sugar high starch diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2009to Sep 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male gender,
- Increased cardio-metabolic risk ('RISCK' criteria Jebb et al (2010) Am J Clin Nutr 92, 748-758).
- Apo E3E3 genotype
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: How Does Dietary Carbohydrate Influence the Formation of an Atherogenic Lipoprotein Phenotype?
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.
Read the 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.
- Being tested
- High sugar low starch diet, Low sugar high starch diet
- Keywords
- Sugars, Fatty liver, Lipoprotein kinetics, Triglycerides
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High sugar low starch dietOther
Low sugar high starch dietOther
| Study group | Role | What they receive |
|---|---|---|
| High sugar low starch diet | Experimental | 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 Receives: Other: High sugar low starch diet; Other: Low sugar high starch diet |
| Low sugar high starch diet | Experimental | 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 Receives: Other: High sugar low starch diet; Other: Low sugar high starch diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Production Rate of VLDL-1 Triacylglycerol (TAG)
The in vivo production rate of VLDL-1 TAG, trace-labelled with [1,1,2,3,3-H5] glycerol, measured in units of grams/day.
Measured: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
Production Rate VLDL-1 Apoprotein B
The in vivo production rate of VLDL-1 apoprotein B, trace-labelled with [I-13C] leucine (leucine with carbon-13), measured in units of milligrams/day.
Measured: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
Secondary outcomes (4)
Kinetics of Systemic Non-esterified Fatty Acids by [C-13]-Trace-labelled Palmitate
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 triacylglycerol in the liver in units of micro mols/L (umol/L).
Measured: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
De Novo Lipogenesis (Rate of Triacylglycerol (TAG) Synthesis in the Liver) as Measured by Contribution to VLDL-1 TAG Production Rate
Acetyl CoA (Co-enzyme-A) is labelled in vivo by the consumption of [2H20] (2H20=deuterated 'heavy'-labelled water). Recovery and detection of this label in VLDL-1 by GC-MS (Gas Chromatography-Mass Spectrometry), provides a measure of fatty acid and TAG synthesis in the liver in terms of its contribution to the production rate of VLDL-1 TAG in units of grams/day.
Measured: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
Intra-hepatocellular Lipid (IHCL) or % Liver Fat
Percentage of intra-hepatocellular lipid (IHCL or % liver fat) was measured by magnetic resonance spectroscopy (MRS).
Measured: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
Plasma Concentration of Triacylglycerol
Plasma concentration of triacylglycerol (TAG) was measured in the post-absorptive state (after 12h fast) and expressed in units of mmol/L (shown as log transformed geometric means)
Measured: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2013 (estimated)
- Study startApr 2009
- Primary completionAug 2011
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-alcoholic Fatty Liver Disease (NAFLD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bruce A. Griffin
- Sponsor type
- University, hospital or other
- Collaborators
- Imperial College London, University of Cambridge
- Responsible party
- Sponsor-investigator, Bruce A. Griffin, University of Surrey
- Investigators
- Bruce A Griffin, PhD, Principal investigator, University of Surrey
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01790984
- Sponsor's protocol ID
- RN0172 A/B
- Other IDs
- BB/G009899/1
- Acronym
- CHOT
- Status last verified
- May 2021
- First submitted
- 11 Feb 2013
- Last updated
- 27 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- How Does Dietary Carbohydrate Influence the Formation of an Atherogenic Lipoprotein Phenotype?
- ClinicalTrials.gov ID
- NCT01790984
- Acronym / sponsor ID
- CHOT / RN0172 A/B
- Keywords
- Sugars, Fatty liver, Lipoprotein kinetics, Triglycerides
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Bruce A. GriffinUniversity, hospital or other
- Collaborators
- Imperial College London, University of Cambridge
- Study start
- Apr 2009
- Primary completion
- Aug 2011 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 13 Feb 2013 (estimated)
- Results
- Posted 27 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High sugar low starch diet | Experimental | Other: High sugar low starch diet, Other: Low sugar high starch dietA 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 |
| Low sugar high starch diet | Experimental | Other: High sugar low starch diet, Other: Low sugar high starch dietA 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male gender,
- Increased cardio-metabolic risk ('RISCK' criteria Jebb et al (2010) Am J Clin Nutr 92, 748-758).
- Apo E3E3 genotype
Key exclusion criteria (8 listed)
- Any abnormal result in blood screen (renal and liver function, haematology)
- Diabetes
- Smoker
- Excessive alcohol consumption (>27units/week)
- Medication likely to affect lipid metabolism
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High sugar low starch diet | Other | High sugar low starch diet, Low sugar high starch diet |
| Low sugar high starch diet | Other | High sugar low starch diet, Low sugar high starch diet |
Primary outcome
Production Rate of VLDL-1 Triacylglycerol (TAG)
Time frame: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
The in vivo production rate of VLDL-1 TAG, trace-labelled with [1,1,2,3,3-H5] glycerol, measured in units of grams/day.
Production Rate VLDL-1 Apoprotein B
Time frame: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
The in vivo production rate of VLDL-1 apoprotein B, trace-labelled with [I-13C] leucine (leucine with carbon-13), measured in units of milligrams/day.
4 secondary outcomes
Kinetics of Systemic Non-esterified Fatty Acids by [C-13]-Trace-labelled Palmitate
Time frame: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
De Novo Lipogenesis (Rate of Triacylglycerol (TAG) Synthesis in the Liver) as Measured by Contribution to VLDL-1 TAG Production Rate
Time frame: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
Intra-hepatocellular Lipid (IHCL) or % Liver Fat
Time frame: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
Plasma Concentration of Triacylglycerol
Time frame: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruce A Griffin, PhD principal investigator
University of Surrey
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High sugar low starch diet and Low sugar high starch diet in people with Non-alcoholic Fatty Liver Disease (NAFLD), run by Bruce A. Griffin at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Production Rate of VLDL-1 Triacylglycerol (TAG) (time frame: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2021.