Fructose Supplementation in Carriers for Hereditary Fructose Intolerance

Hereditary Fructose Intolerance Clinical Trial

Official title:

Metabolic Effects of Short-term Dietary Supplementation With Fructose in Carriers for Hereditary Fructose Intolerance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03545581
• Other study ID #: 2016-00289
• Status: Completed
• Phase: N/A
• Start date: May 1, 2018
• Est. completion date: April 1, 2019

Study information

• Verified date: April 2019
• Source: University of Lausanne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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, crossover trial.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: April 1, 2019
• Est. primary completion date: December 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Fructose Intolerance
• Hereditary Fructose Intolerance

Intervention

Other:
• Experimental diet Fru rich diet
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 diet
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)

Locations

Country	Name	City	State
Belgium	Guillaume Debray	Liège

Sponsors (2)

Lead Sponsor	Collaborator
University of Lausanne	University Hospital of Liege

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary	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	Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary	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	Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary	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	Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary	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	Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary	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	Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary	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	Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary	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	Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary	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	Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary	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	Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary	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	Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary	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	Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary	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	Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary	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	Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary	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	Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
Secondary	Urine metabolome concentration	Change in urine metabolome profile after low fructose diet and an enriched fructose diet according to a crossover design	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
Secondary	Urine creatinine concentration	Change in urine creatinine profile after low fructose diet and an enriched fructose diet according to a crossover design	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
Secondary	Urine urea concentration	Change in urine urea profile after low fructose diet and an enriched fructose diet according to a crossover design	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
Secondary	Urine uric acid concentration	Change in urine uric acid profile after low fructose diet and an enriched fructose diet according to a crossover design	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
Secondary	Body weight	Change of body weight after low fructose diet and an enriched fructose diet according to a crossover design	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
Secondary	Blood pressure	Change of systolic and diastolic pressure after low fructose diet and an enriched fructose diet according to a crossover design	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