Clinical trial NCT02979106: Metabolic Consequences of Heterozygous Hereditary Fructose Intolerance
Official title: Are Heterozygous Carriers for Hereditary Fructose Intolerance Predisposed to Metabolic Disturbances When Exposed to Fructose?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hereditary Fructose Intolerance
Fructose Metabolism, Inborn Errors
Glucose Metabolism Disorders
Lead sponsor: University of Lausanne
Sponsor class: OTHER
First posted: 2016-12-01
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Background: High fructose intake increases blood lactate, triglyceride and uric acid concentrations. Uric acid may contribute to insulin resistance and dyslipidemia in the general population. In patients with hereditary fructose intolerance fructose consumption is associated with acute hypoglycemia, renal tubular acidosis, and hyperuricemia.

Objective: We investigated whether asymptomatic carriers for hereditary fructose intolerance (HFI) would have a higher sensitivity to adverse effects of fructose than the general population.

Design: Eight subjects heterozygous for HFI (hHFI; 4 males, 4 females) and eight controls received for 7 days a low fructose diet and on the eighth day ingested a test meal calculated to provide 25% of basal energy requirement containing labeled fructose (13C fructose 0.35 g/kg), protein (0.21 g/kg) and lipid (0.22 g/kg). Total fructose oxidation, total endogenous glucose production (by 6,6-2H2-glucose dilution), carbohydrate and lipid oxidation, lipids, uric acid, lactate, creatinine, urea and amino acids were monitored for 6 hours.


Eligibility criteria: Inclusion Criteria:

* 8 healthy Volunteers (4 male, 4 female) parents of a child with hereditary fructose intolerance with ALDOB with heterozygous mutation of ALDOB gene
* 8 healthy Volunteers (4 male, 4 female), healthy with no mutation of ALDOB gene

Exclusion Criteria:

* Fasting glycemia \> 7.0 mmol/L
* Fasting total triglycerides \> 4.0 mmol/L
* Chronic renal insufficiency (eGFR ≤ 50 ml/min)
* Anemia (ferritin \< 20 ug/L, hemoglobin \< 13.5 ou 12.5 g/dl)
* Drugs
* Pregnancy

Primary outcomes:
measure: Plasma glucose kinetics
timeFrame: -120 min before ingestion of a test meal to 360 min after ingestion of a test meal
Secondary outcomes:
measure: Energy expenditure rate
timeFrame: 120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal
measure: Glucose oxidation rate
timeFrame: 120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal
measure: Plasma glucose concentration
timeFrame: -120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal
measure: plasma insulin concentration
timeFrame: -120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal
measure: Fructose oxidation
timeFrame: Every 30 min until 360 min after ingestion of a test meal
Other outcomes:
Locations:
Study officials:
affiliation: University of Lausanne
name: Tappy Luc, MD
role: STUDY_DIRECTOR
References:
citation: Debray FG, Damjanovic K, Rosset R, Mittaz-Crettol L, Roux C, Braissant O, Barbey F, Bonafe L, De Bandt JP, Tappy L, Paquot N, Tran C. Are heterozygous carriers for hereditary fructose intolerance predisposed to metabolic disturbances when exposed to fructose? Am J Clin Nutr. 2018 Aug 1;108(2):292-299. doi: 10.1093/ajcn/nqy092.