Fructose Supplementation in Carriers for Hereditary Fructose Intolerance

April 19, 2019 updated by: Christel Tran, University of Lausanne

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.

Study Overview

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 Type

Interventional

Enrollment (Actual)

12

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Liège, Belgium
        • Guillaume Debray

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Experimental diet Fru rich diet
Enriched fructose diet from day 1 to day 7.
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)
Other: Experimental low Fru diet
Low fructose diet from day 1 to day 7.
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma glucose concentration
Time Frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
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
Plasma insulin concentration
Time Frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
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
Plasma fructose concentration
Time Frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
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
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
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
Plasma lactate concentration
Time Frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
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
Plasma urea concentration
Time Frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
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
Plasma creatinine concentration
Time Frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
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
Plasma phosphate concentration
Time Frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
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
Plasma triglycerides concentration
Time Frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
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
Plasma metabolome concentration
Time Frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
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
Plasma ammonia concentration
Time Frame: Time Frame: -30 min before ingestion of a test meal to 120 min after ingestion of a test meal
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2018

Primary Completion (Actual)

December 1, 2018

Study Completion (Actual)

April 1, 2019

Study Registration Dates

First Submitted

May 7, 2018

First Submitted That Met QC Criteria

May 22, 2018

First Posted (Actual)

June 4, 2018

Study Record Updates

Last Update Posted (Actual)

April 22, 2019

Last Update Submitted That Met QC Criteria

April 19, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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