Hereditary Fructose IntoleranceNCT03545581
Fructose Supplementation in Carriers for Hereditary Fructose Intolerance
A study testing Experimental diet Fru rich diet and Experimental low Fru diet in people with Hereditary Fructose Intolerance, run by University of Lausanne at 1 site in Belgium.
Trial summary
This study aimed to examine metabolic response to a short-term fructose enriched diet in carriers for hereditary fructose intolerance compared to controls. Effects of fructose coffees will be assessed in 7 healthy volunteers and 7 subjects with heterozygous mutation for ALDOB gene in a randomized, controlled… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hereditary Fructose Intolerance
- What is being tested?
- Experimental diet Fru rich diet and Experimental low Fru diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteBelgium
- Study dates
- 1 May 2018to 1 Apr 2019
- 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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Case subjects: Heterozygous carriers for ALDOB mutation confirmed by molecular analysis
- Control subjects: healthy individuals matched for weight and age to subjects
Who cannot join
- Fasting glucose > 7.0 mmol/L
- Fasting triglycerides > 4.0 mmol/L
- Chronic renal insufficiency (eGFR < 50 ml/min)
- Drugs
- Women who are pregnant or breast feeding
- For women: lack of safe contraception
- Alcool consumption > 30g/d
- Inability to discern
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Metabolic Effects of Short-term Dietary Supplementation With Fructose in Carriers for Hereditary Fructose Intolerance
This study aimed to examine metabolic response to a short-term fructose enriched diet in carriers for hereditary fructose intolerance compared to controls. Effects of fructose coffees will be assessed in 7 healthy volunteers and 7 subjects with heterozygous mutation for ALDOB gene in a randomized, controlled, crossover trial.
Read the detailed description
A high fructose intake also increases blood lactate and uric acid concentrations. It has been proposed that uric acid may contribute to insulin resistance by impairing endothelium-dependent vasodilation, promoting pro-inflammatory effects and dyslipidemia by activating de novo lipogenesis.
These consequences of fructose overconsumption may be even more marked in individuals with hereditary alterations in fructose metabolism. Indeed, individuals with hereditary fructose intolerance (HFI), due to biallelic mutations in the gene coding for aldolase B (ALDOB), may develop acute, life-threatening manifestations when exposed to fructose. Heterozygous carriers of ALDOB mutation are quite common in the general population, with a predicted frequency ranging between 1:55 and 1:120. Few studies have examined the effect of fructose ingestion in heterozygotes subject for HFI. Heterozygous carriers are generally considered to have normal fructose metabolism since a ~ 50% level of aldolase B activity is presumed to be sufficient for adequate function. However, heterozygous carriers were reported to have enhanced uric acid responses to large intravenous and/or oral fructose loads.
Investigators hypothesized that heterozygous carriers may also have mild defects of fructose metabolism and/or a larger increase in cardiometabolic risk factors than the normal population after ingestion of moderate amounts of fructose.
- Conditions
- Hereditary Fructose Intolerance
- Being tested
- Experimental diet Fru rich diet, Experimental low Fru diet
- Keywords
- Fructose, Uric acid, Glucose homeostasis
- Medical subject headings
- Fructose Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experimental diet Fru rich dietOther
7 days (day 1 to day 7) with fructose enriched drinks 3x/d. Test meal at day 7 with fructose (0.7 g/body weight) and glucose (0.7 g/body weight)
Experimental low Fru dietOther
7 days (day 1 to day 7) with low-fructose diet (<10g/d). Test meal at day 7 with fructose (0.7 g/body weight) and glucose (0.7 g/body weight)
| Study group | Role | What they receive |
|---|---|---|
| Experimental diet Fru rich diet | Other | Enriched fructose diet from day 1 to day 7. Receives: Other: Experimental diet Fru rich diet |
| Experimental low Fru diet | Other | Low fructose diet from day 1 to day 7. Receives: Other: Experimental low Fru diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metabolite concentration
The primary endpoint is the change of metabolite concentration after ingestion of a test meal (oral glucose and fructose load) under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Measured: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary outcomes (20)
Plasma glucose concentration
Change in glucose concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Measured: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma insulin concentration
Change in insulin concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Measured: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma fructose concentration
Change in fructose concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Measured: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma uric acid concentration
Change in uric acid concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Measured: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma lactate concentration
Change in lactate concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Measured: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma urea concentration
Change in urea concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Measured: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma creatinine concentration
Change in creatinine concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Measured: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma phosphate concentration
Change in phosphate concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Measured: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma triglycerides concentration
Change in triglycerides concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Measured: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma metabolome concentration
Change in metabolome concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Measured: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma ammonia concentration
Change in ammonia concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Measured: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma amino acid concentration
Change in amino acid concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Measured: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma alanine transaminase (ALAT) concentration
Change in alanine transminase (ALAT) concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Measured: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma aspartate transaminase (ASAT) concentration
Change in aspartate transaminase (ASAT) concentration after ingestion of a test meal under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Measured: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Urine metabolome concentration
Change in urine metabolome profile after low fructose diet and an enriched fructose diet according to a crossover design
Measured: Time Frame: 24 hour urine collection before ingestion of a test meal and after 7 days of 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Urine creatinine concentration
Change in urine creatinine profile after low fructose diet and an enriched fructose diet according to a crossover design
Measured: Time Frame: 24 hour urine collection before ingestion of a test meal and after 7 days of 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Urine urea concentration
Change in urine urea profile after low fructose diet and an enriched fructose diet according to a crossover design
Measured: Time Frame: 24 hour urine collection before ingestion of a test meal and after 7 days of 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Urine uric acid concentration
Change in urine uric acid profile after low fructose diet and an enriched fructose diet according to a crossover design
Measured: Time Frame: 24 hour urine collection before ingestion of a test meal and after 7 days of 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Body weight
Change of body weight after low fructose diet and an enriched fructose diet according to a crossover design
Measured: Time Frame: at baseline before study intervention and at the end of each conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Blood pressure
Change of systolic and diastolic pressure after low fructose diet and an enriched fructose diet according to a crossover design
Measured: Time Frame: at baseline before study intervention and at the end of each conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2018
- Study start1 May 2018
- Primary completion1 Dec 2018
- Study completion1 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary Fructose IntoleranceStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Lausanne
- Sponsor type
- University, hospital or other
- Collaborators
- University of Liege
- Responsible party
- Principal investigator, Christel Tran, University of Lausanne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03545581
- Sponsor's protocol ID
- 2016-00289
- Other IDs
- 2016
- Status last verified
- Apr 2019
- First submitted
- 7 May 2018
- Last updated
- 22 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Debray FG, Seyssel K, Fadeur M, Tappy L, Paquot N, Tran C. Effect of a high fructose diet on metabolic parameters in carriers for hereditary fructose intolerance. Clin Nutr. 2021 Jun;40(6):4246-4254. doi: 10.1016/j.clnu.2021.01.026. Epub 2021 Jan 27.
PubMed 33551217
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Effects of Short-term Dietary Supplementation With Fructose in Carriers for Hereditary Fructose Intolerance
- ClinicalTrials.gov ID
- NCT03545581
- Acronym / sponsor ID
- 2016-00289
- Conditions
- Hereditary Fructose Intolerance
- Keywords
- Fructose, Uric acid, Glucose homeostasis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of LausanneUniversity, hospital or other
- Collaborators
- University of Liege
- Study start
- 1 May 2018 (actual)
- Primary completion
- 1 Dec 2018 (actual)
- Study completion
- 1 Apr 2019 (actual)
- First posted
- 4 Jun 2018 (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.
This study aimed to examine metabolic response to a short-term fructose enriched diet in carriers for hereditary fructose intolerance compared to controls. Effects of fructose coffees will be assessed in 7 healthy volunteers and 7 subjects with heterozygous mutation for ALDOB gene in a randomized, controlled, crossover trial.
Detailed description
A high fructose intake also increases blood lactate and uric acid concentrations. It has been proposed that uric acid may contribute to insulin resistance by impairing endothelium-dependent vasodilation, promoting pro-inflammatory effects and dyslipidemia by activating de novo lipogenesis.
These consequences of fructose overconsumption may be even more marked in individuals with hereditary alterations in fructose metabolism. Indeed, individuals with hereditary fructose intolerance (HFI), due to biallelic mutations in the gene coding for aldolase B (ALDOB), may develop acute, life-threatening manifestations when exposed to fructose. Heterozygous carriers of ALDOB mutation are quite common in the general population, with a predicted frequency ranging between 1:55 and 1:120. Few studies have examined the effect of fructose ingestion in heterozygotes subject for HFI. Heterozygous carriers are generally considered to have normal fructose metabolism since a ~ 50% level of aldolase B activity is presumed to be sufficient for adequate function. However, heterozygous carriers were reported to have enhanced uric acid responses to large intravenous and/or oral fructose loads.
Investigators hypothesized that heterozygous carriers may also have mild defects of fructose metabolism and/or a larger increase in cardiometabolic risk factors than the normal population after ingestion of moderate amounts of fructose.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental diet Fru rich diet | Other | Other: Experimental diet Fru rich dietEnriched fructose diet from day 1 to day 7. |
| Experimental low Fru diet | Other | Other: Experimental low Fru dietLow fructose diet from day 1 to day 7. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Case subjects: Heterozygous carriers for ALDOB mutation confirmed by molecular analysis
- Control subjects: healthy individuals matched for weight and age to subjects
Key exclusion criteria (8 listed)
- Fasting glucose > 7.0 mmol/L
- Fasting triglycerides > 4.0 mmol/L
- Chronic renal insufficiency (eGFR < 50 ml/min)
- Drugs
- Women who are pregnant or breast feeding
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 |
|---|---|---|
| Experimental diet Fru rich diet7 days (day 1 to day 7) with fructose enriched drinks 3x/d. Test meal at day 7 with fructose (0.7 g/body weight) and glucose (0.7 g/body weight) | Other | Experimental diet Fru rich diet |
| Experimental low Fru diet7 days (day 1 to day 7) with low-fructose diet (<10g/d). Test meal at day 7 with fructose (0.7 g/body weight) and glucose (0.7 g/body weight) | Other | Experimental low Fru diet |
Primary outcome
Metabolite concentration
Time frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
The primary endpoint is the change of metabolite concentration after ingestion of a test meal (oral glucose and fructose load) under 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
20 secondary outcomes
Plasma glucose concentration
Time frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma insulin concentration
Time frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma fructose concentration
Time frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma uric acid concentration
Time frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma lactate concentration
Time frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma urea concentration
Time frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma creatinine concentration
Time frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma phosphate concentration
Time frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma triglycerides concentration
Time frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma metabolome concentration
Time frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma ammonia concentration
Time frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma amino acid concentration
Time frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma alanine transaminase (ALAT) concentration
Time frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Plasma aspartate transaminase (ASAT) concentration
Time frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Urine metabolome concentration
Time frame: Time Frame: 24 hour urine collection before ingestion of a test meal and after 7 days of 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Urine creatinine concentration
Time frame: Time Frame: 24 hour urine collection before ingestion of a test meal and after 7 days of 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Urine urea concentration
Time frame: Time Frame: 24 hour urine collection before ingestion of a test meal and after 7 days of 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Urine uric acid concentration
Time frame: Time Frame: 24 hour urine collection before ingestion of a test meal and after 7 days of 2 conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Body weight
Time frame: Time Frame: at baseline before study intervention and at the end of each conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Blood pressure
Time frame: Time Frame: at baseline before study intervention and at the end of each conditions (enriched fructose diet vs poor fructose diet) according to a crossover design
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2019.
- Derived from this study: PubMed 33551217Debray FG, Seyssel K, Fadeur M, Tappy L, Paquot N, Tran C. Effect of a high fructose diet on metabolic parameters in carriers for hereditary fructose intolerance. Clin Nutr. 2021 Jun;40(6):4246-4254. doi: 10.1016/j.clnu.2021.01.026. Epub 2021 Jan 27.
Related trials for Hereditary Fructose Intolerance
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
Not yet recruiting
New Microbiota-endocrine Axis in Fructose Malabsorption-caused Visceral Hypersensitivity in Irritable Bowel Syndrome.
Irritable Bowel Syndrome (IBS)
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Experimental diet Fru rich diet and Experimental low Fru diet in people with Hereditary Fructose Intolerance, run by University of Lausanne at 1 site in Belgium.
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 2 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 22 Apr 2019. 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 Belgium. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Metabolite concentration (time frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03545581, which also lists 1 linked publication.
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 22 Apr 2019.