Fructose Supplementation in Carriers for Hereditary Fructose Intolerance

NCT ID: NCT03545581

Last Updated: 2019-04-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-01
• Study Completion Date: 2019-04-01

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.

Conditions

Hereditary Fructose Intolerance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Experimental diet Fru rich diet

Enriched fructose diet from day 1 to day 7.

Group Type: OTHER

Experimental diet Fru rich diet

Intervention Type: OTHER

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

Low fructose diet from day 1 to day 7.

Group Type: OTHER

Experimental low Fru diet

Intervention Type: OTHER

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)

Interventions

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)

Intervention Type: OTHER

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)

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Liege

OTHER

Sponsor Role: collaborator

University of Lausanne

OTHER

Sponsor Role: lead

Responsible Party

Christel Tran

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Guillaume Debray

Liège, , Belgium

Countries

Belgium

References

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.

Reference Type: DERIVED

PMID: 33551217 (View on PubMed)

Other Identifiers

2016-00289

Identifier Type: -

Identifier Source: org_study_id