Non-alcoholic Fatty Liver DiseaseFLYNCT05528471
Fructose and Liver Diseases in Youth: Help Them FLY
A study testing Dietary intervention in people with Non-alcoholic Fatty Liver Disease, run by University of Alberta at 1 site in Canada.
Trial summary
Obesity has been increasing all over the world. This has lead to a significant increase of a liver disease in children called non-alcoholic fatty liver disease (NAFLD). NAFLD is a liver disease that ranges from excess fat being stored in the liver to an inflamed and fatty liver with fibrosis to cirrhosis. Read more about this study
- Who is it for?
- Ages 12 to 18 years
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease
- What is being tested?
- Dietary intervention
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteCanada
- Study dates
- 30 Apr 2015to 30 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 12 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- obese boys and girls aged 12-18 years (Tanner Stage: III-V) with clinically diagnosed NAFLD
Who cannot join
- all patients with a history of a known primary liver disease associated with steatohepatitis (Wilson disease, various metabolic disorders, viral hepatitis) (7);
- All patients with a known primary diagnosis of Type 2 Diabetes or those on insulin;
- Patients on medications known to cause hepatic steatosis (e.g., methotrexate, corticosteroids, valproic acid, statins);
- Patients with evidence of bridging fibrosis (8); and
- Patients with a known significant history of smoking or alcohol consumption (6, 9) and
- Any patient undergoing an active weight loss program and/or who has received bariatric surgery for the treatment of obesity
Show all 9Show fewer
- Any participant with a cardiac pacemaker or with metal pins as this is a contraindication for MRS/MRI testing
- Any participant of child bearing potential who is known to be pregnant (as this is a contraindication to MRS/MRI) testing. All females of child bearing potential will be asked to undergo a routine pregnancy test (urine) prior to MRS/MRI testing. This will be conducted in the baseline study visit
- Any child with significant developmental delay or a significant co-morbidity that precluded the ability to participate in study procedures
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Clinical Research Unit, University of Alberta
Edmonton, Alberta, T6G 0K2
Diana R Mager, PhD RD
About this study
Official title: Dietary Fructose as a Mediator to Altered Liver Energy Metabolism and Oxidative Stress in Youth With Non-alcoholic Fatty Liver Disease: HELP THEM FLY.
Obesity has been increasing all over the world. This has lead to a significant increase of a liver disease in children called non-alcoholic fatty liver disease (NAFLD). NAFLD is a liver disease that ranges from excess fat being stored in the liver to an inflamed and fatty liver with fibrosis to cirrhosis. NAFLD is thought to be caused by changes in energy, fat and carbohydrate metabolism induced by diets high in in processed foods. Sugary (especially high fructose corn syrup or HFCS) and fatty foods in processed foods have been shown to produce more insulin resistance, a factor that is thought to cause a fatty liver. Currently the main treatment for NAFLD is weight loss. However, it unknown the best way to achieve this. The investigator has shown previously that adolescents with NAFLD eat a lot of fatty and sugary foods, and that when they decrease the amount of foods they eat that contain HFCS, experience some improvements in insulin resistance and liver dysfunction even when they don't lose weight. The plan is to compare and contrast how two different diets (high vs low HFCS containing diets) may affect how much fat gets deposited in the liver and whether or not a lower diet in HFCS can help decrease liver damage in adolescents with NAFLD.
Read the detailed description
Study Rationale: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease estimated to occur in 10-20% of obese children and adults. High fructose and saturated fat intakes are thought to be major dietary factors contributing to over nutrition, insulin resistance, cardio-metabolic risk (e.g dysplipidemia, hypertension) and disease pathogenesis in adults and children with NAFLD . Although weight loss is the goal of treatment, there are currently no evidence based clinical guidelines regarding the specific dietary treatment needed for NAFLD. The investigator has shown previously that children and adolescents with NAFLD have diets rich in both total fructose (>10% of total energy intake) and high fructose corn syrup (20-50% of total fructose intake. These levels of intake were associated with increasing indices of liver dysfunction, insulin resistance and inflammation. In a recent pilot study, the investigator has showed that children with NAFLD experienced significant reductions in systolic blood pressure, percentage body fat, plasma markers of liver dysfunction (ALT, AST), cardio-metabolic risk (HOMA-IR, AI-IR, TG, Apo-B100) and alterations in body fat distribution in response to six months of an iso-caloric/low fructose diet (~5% of total kcal). High levels of fructose in the diet have been independently associated with insulin resistance, visceral adiposity, hepatic and skeletal muscle intramyocellular fat (IMF) deposition, altered hepatic mitochondrial function and energy utilization (ATP depletion), increased rates of de novo lipogenesis, inflammation, and hepatic fibrosis in both animal models and adults with NAFLD. While adult studies in NAFLD have related the impact of high intakes of HFCS to altered liver energetics (ATP production) and increasing insulin resistance and IMF , this has not be studied in obese children and adolescents with NAFLD. In addition, no information is available regarding the impact of dietary fructose reductions on these processes in either obese children, adolescents or adults with NAFLD. The plan is to use validated, non-invasive and safe methodologies such as Magnetic Resonance Imaging (MRI) and Magnetic Resonance Stimulation (MRS) to compare and contrast the effects of varying fructose intakes (low vs high) in iso-caloric diets on liver mitochondrial energetic (ATP production), hepatic and skeletal muscle fat content and markers of cardio-metabolic risk, liver dysfunction, insulin resistance, inflammation and oxidative stress in adolescents with NAFLD.
Hypotheses
- Obese adolescents with NAFLD treated with a low fructose /low HFCS diet over 12 weeks, in the absence of weight loss, will result in significant improvements in indices of hepatic ATP production and reduced liver/ skeletal muscle fat deposition when compared to the effects of a higher fructose/higher HFCS diet.
- Obese adolescents with NAFLD treated with a low fructose /low HFCS diet over 12 weeks, in the absence of weight loss, will result in significant improvements in indices of visceral and subcutaneous adiposity, insulin resistance and markers of liver and cardio-metabolic dysfunction, inflammation and oxidative stress when compared to the effects of a higher fructose/higher HFCS diet.
- Conditions
- Non-alcoholic Fatty Liver Disease
- Being tested
- Dietary intervention
- Keywords
- Non-alcoholic fatty liver disease, Fructose, Hepatic energetics, Hepatic fat fraction, Adolescents
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dietary interventionOther
Also called Fructose intervention
To compare an iso-caloric, low fructose diet (~5% of total energy intake (TEI); HFCS max: 10-15% of total fructose intake) to an iso-caloric, higher fructose diet (~10% of TEI; HFCS max 20-30% of total fructose intake) in adolescents with NAFLD. The 10% higher fructose diet is part of standard of care and is NOT the intervention.
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | Iso-caloric and low fructose /low HFCS diet (~5% of total energy intake (TEI); HFCS max: 10-15% of total fructose intake) (n=35) Receives: Other: Dietary intervention |
| Control group | No intervention | Iso-caloric with higher fructose diet (~10% of TEI; HFCS max 20-30% of total fructose intake) (n=35) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in 31P spectra from abdominal MRI scans in response to dietary intervention.
Changes in area under the curve (AUC) for 31P spectra obtained from abdominal Magnetic Resonance Scan between baseline and 3 months between individuals and between study arms. We will calculate the difference (baseline value-3 months value) for each individual to determine the change from baseline. This will be done in both groups.
Measured: Change from baseline to 3 months
Secondary outcomes (5)
Change in hepatic intramyocellular surface area in response to dietary intervention.
Hepatic intramyocellular surface area (cm3/ht2) as measured by abdominal 1H1-Spectra obtained from Magnetic Resonance scans between baseline and 3 months between individuals and between study arms.The calculation for each value will (baseline value - 3 month value) for each individual. Unit have been provided in the description.
Measured: Change from baseline to 3 months
Change in visceral adipose tissue (VAT cm3/ht2) and subcutaneous adipose tissue (SAT cm3/ht2) surface area in response to the dietary intervention
Changes in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) as measured from abdominal 1H1-abdominal MRI scans content/distribution between baseline and 3 months between individuals and between study arms.The calculation for each value will (baseline value - 3 month value) for SAT (cm3/height 2) and VAT (cm3/height2). . Unit have been provided in the description.
Measured: Change from baseline to 3 months
Change in markers of liver dysfunction in response to the dietary intervention
Serum AST (U/L), ALT (U/L), GGT (U/L) between baseline and 3 months between individuals and between study arms. The calculation for each value will (baseline value - 3 month value) for each individual blood work. Unit have been provided in the description.
Measured: Change from baseline to 3 months
Change in cardio-metabolic risk factors in response to the dietary intervention
Serum triglycerides (mmol/L) total cholesterol, HDL-and LDL cholesterol (mmol/L)) between baseline and 3 months between individuals and between study arms. The calculation for each value will (baseline value - 3 month value) for each individual blood work. Unit have been provided in the description.
Measured: Change from baseline to 3 months
Change in measures of insulin resistance in response to the dietary intervention
Changes in markers of insulin resistance (serum insulin mU/L, HOMA-IR) between baseline and 3 months between individuals and between study arms. HOMA-IR is calculated by the following equation. HOMA-IR=fasting glucose in mmol/l*fasting insulin in μU/ml/22.5. The calculation for each value will (baseline value - 3 month value) for each individual blood work. Unit have been provided in the description.
Measured: Change from baseline to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2022
- Study start30 Apr 2015
- Primary completion30 Dec 2024 (estimated)
- Study completion30 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- Alberta Health services, Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Diana R Mager, PhD RD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05528471
- Sponsor's protocol ID
- Pro00049795
- Acronym
- FLY
- Status last verified
- Oct 2024
- First submitted
- 15 Sep 2020
- Last updated
- 9 Oct 2024
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dietary Fructose as a Mediator to Altered Liver Energy Metabolism and Oxidative Stress in Youth With Non-alcoholic Fatty Liver Disease: HELP THEM FLY.
- ClinicalTrials.gov ID
- NCT05528471
- Acronym / sponsor ID
- FLY / Pro00049795
- Conditions
- Non-alcoholic Fatty Liver Disease
- Keywords
- Non-alcoholic fatty liver disease, Fructose, Hepatic energetics, Hepatic fat fraction, Adolescents
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Collaborators
- Alberta Health services, Canadian Institutes of Health Research (CIHR)
- Study start
- 30 Apr 2015 (actual)
- Primary completion
- 30 Dec 2024 (estimated)
- Study completion
- 30 Dec 2024 (estimated)
- First posted
- 6 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Obesity has been increasing all over the world. This has lead to a significant increase of a liver disease in children called non-alcoholic fatty liver disease (NAFLD). NAFLD is a liver disease that ranges from excess fat being stored in the liver to an inflamed and fatty liver with fibrosis to cirrhosis. NAFLD is thought to be caused by changes in energy, fat and carbohydrate metabolism induced by diets high in in processed foods. Sugary (especially high fructose corn syrup or HFCS) and fatty foods in processed foods have been shown to produce more insulin resistance, a factor that is thought to cause a fatty liver. Currently the main treatment for NAFLD is weight loss. However, it unknown the best way to achieve this. The investigator has shown previously that adolescents with NAFLD eat a lot of fatty and sugary foods, and that when they decrease the amount of foods they eat that contain HFCS, experience some improvements in insulin resistance and liver dysfunction even when they don't lose weight. The plan is to compare and contrast how two different diets (high vs low HFCS containing diets) may affect how much fat gets deposited in the liver and whether or not a lower diet in HFCS can help decrease liver damage in adolescents with NAFLD.
Detailed description
Study Rationale: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease estimated to occur in 10-20% of obese children and adults. High fructose and saturated fat intakes are thought to be major dietary factors contributing to over nutrition, insulin resistance, cardio-metabolic risk (e.g dysplipidemia, hypertension) and disease pathogenesis in adults and children with NAFLD . Although weight loss is the goal of treatment, there are currently no evidence based clinical guidelines regarding the specific dietary treatment needed for NAFLD. The investigator has shown previously that children and adolescents with NAFLD have diets rich in both total fructose (>10% of total energy intake) and high fructose corn syrup (20-50% of total fructose intake. These levels of intake were associated with increasing indices of liver dysfunction, insulin resistance and inflammation. In a recent pilot study, the investigator has showed that children with NAFLD experienced significant reductions in systolic blood pressure, percentage body fat, plasma markers of liver dysfunction (ALT, AST), cardio-metabolic risk (HOMA-IR, AI-IR, TG, Apo-B100) and alterations in body fat distribution in response to six months of an iso-caloric/low fructose diet (~5% of total kcal). High levels of fructose in the diet have been independently associated with insulin resistance, visceral adiposity, hepatic and skeletal muscle intramyocellular fat (IMF) deposition, altered hepatic mitochondrial function and energy utilization (ATP depletion), increased rates of de novo lipogenesis, inflammation, and hepatic fibrosis in both animal models and adults with NAFLD. While adult studies in NAFLD have related the impact of high intakes of HFCS to altered liver energetics (ATP production) and increasing insulin resistance and IMF , this has not be studied in obese children and adolescents with NAFLD. In addition, no information is available regarding the impact of dietary fructose reductions on these processes in either obese children, adolescents or adults with NAFLD. The plan is to use validated, non-invasive and safe methodologies such as Magnetic Resonance Imaging (MRI) and Magnetic Resonance Stimulation (MRS) to compare and contrast the effects of varying fructose intakes (low vs high) in iso-caloric diets on liver mitochondrial energetic (ATP production), hepatic and skeletal muscle fat content and markers of cardio-metabolic risk, liver dysfunction, insulin resistance, inflammation and oxidative stress in adolescents with NAFLD.
Hypotheses
- Obese adolescents with NAFLD treated with a low fructose /low HFCS diet over 12 weeks, in the absence of weight loss, will result in significant improvements in indices of hepatic ATP production and reduced liver/ skeletal muscle fat deposition when compared to the effects of a higher fructose/higher HFCS diet.
- Obese adolescents with NAFLD treated with a low fructose /low HFCS diet over 12 weeks, in the absence of weight loss, will result in significant improvements in indices of visceral and subcutaneous adiposity, insulin resistance and markers of liver and cardio-metabolic dysfunction, inflammation and oxidative stress when compared to the effects of a higher fructose/higher HFCS diet.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Experimental | Other: Dietary interventionIso-caloric and low fructose /low HFCS diet (~5% of total energy intake (TEI); HFCS max: 10-15% of total fructose intake) (n=35) |
| Control group | No intervention | –Iso-caloric with higher fructose diet (~10% of TEI; HFCS max 20-30% of total fructose intake) (n=35) |
Who may qualify
- Ages
- 12 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- obese boys and girls aged 12-18 years (Tanner Stage: III-V) with clinically diagnosed NAFLD
Key exclusion criteria (9 listed)
- all patients with a history of a known primary liver disease associated with steatohepatitis (Wilson disease, various metabolic disorders, viral hepatitis) (7);
- All patients with a known primary diagnosis of Type 2 Diabetes or those on insulin;
- Patients on medications known to cause hepatic steatosis (e.g., methotrexate, corticosteroids, valproic acid, statins);
- Patients with evidence of bridging fibrosis (8); and
- Patients with a known significant history of smoking or alcohol consumption (6, 9) and
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 |
|---|---|---|
| Dietary interventionAlso: Fructose interventionTo compare an iso-caloric, low fructose diet (~5% of total energy intake (TEI); HFCS max: 10-15% of total fructose intake) to an iso-caloric, higher fructose diet (~10% of TEI; HFCS max 20-30% of total fructose intake) in adolescents with NAFLD. The 10% higher fructose diet is part of standard of care and is NOT the intervention. | Other | Intervention group |
Primary outcome
Change in 31P spectra from abdominal MRI scans in response to dietary intervention.
Time frame: Change from baseline to 3 months
Changes in area under the curve (AUC) for 31P spectra obtained from abdominal Magnetic Resonance Scan between baseline and 3 months between individuals and between study arms. We will calculate the difference (baseline value-3 months value) for each individual to determine the change from baseline. This will be done in both groups.
5 secondary outcomes
Change in hepatic intramyocellular surface area in response to dietary intervention.
Time frame: Change from baseline to 3 months
Change in visceral adipose tissue (VAT cm3/ht2) and subcutaneous adipose tissue (SAT cm3/ht2) surface area in response to the dietary intervention
Time frame: Change from baseline to 3 months
Change in markers of liver dysfunction in response to the dietary intervention
Time frame: Change from baseline to 3 months
Change in cardio-metabolic risk factors in response to the dietary intervention
Time frame: Change from baseline to 3 months
Change in measures of insulin resistance in response to the dietary intervention
Time frame: Change from baseline to 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2024.
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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.
Diana R Mager, PhD RD principal investigator
University of Alberta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dietary intervention in people with Non-alcoholic Fatty Liver Disease, run by University of Alberta at 1 site in Canada.
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 1 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 9 Oct 2024. 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 Canada. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Diana R Mager, PhD RD (780-492-7687, mager@ualberta.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in 31P spectra from abdominal MRI scans in response to dietary intervention. (time frame: Change from baseline to 3 months). 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 9 Oct 2024.