Clinical trial NCT03545581: Fructose Supplementation in Carriers for Hereditary Fructose Intolerance
Official title: Metabolic Effects of Short-term Dietary Supplementation With Fructose in Carriers for Hereditary Fructose Intolerance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hereditary Fructose Intolerance
Keywords: Fructose
Uric acid
Glucose homeostasis
Lead sponsor: University of Lausanne
Sponsor class: OTHER
Collaborators: name: University of Liege
First posted: 2018-06-04
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief 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, 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.

Eligibility criteria: Inclusion Criteria:

* Case subjects: Heterozygous carriers for ALDOB mutation confirmed by molecular analysis
* Control subjects: healthy individuals matched for weight and age to subjects

Exclusion Criteria:

* 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

Primary outcomes:
measure: Metabolite concentration
timeFrame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary outcomes:
measure: Plasma glucose concentration
timeFrame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
measure: Plasma insulin concentration
timeFrame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
measure: Plasma fructose concentration
timeFrame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
measure: Plasma uric acid concentration
timeFrame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
measure: Plasma lactate concentration
timeFrame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
measure: Plasma urea concentration
timeFrame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
measure: Plasma creatinine concentration
timeFrame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
measure: Plasma phosphate concentration
timeFrame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
measure: Plasma triglycerides concentration
timeFrame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
measure: Plasma metabolome concentration
timeFrame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
measure: Plasma ammonia concentration
timeFrame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
measure: Plasma amino acid concentration
timeFrame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
measure: Plasma alanine transaminase (ALAT) concentration
timeFrame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
measure: Plasma aspartate transaminase (ASAT) concentration
timeFrame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
measure: Urine metabolome concentration
timeFrame: 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
measure: Urine creatinine concentration
timeFrame: 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
measure: Urine urea concentration
timeFrame: 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
measure: Urine uric acid concentration
timeFrame: 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
measure: Body weight
timeFrame: 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
measure: Blood pressure
timeFrame: 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
Other outcomes:
Locations:
city: Liège
country: Belgium
facility: Guillaume Debray
Study officials:
References:
citation: 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.