Metabolic Consequences of Heterozygous Hereditary Fructose Intolerance

• Sponsor: University of Lausanne (Other)
• Overall Status: Completed
• CT.gov ID: NCT02979106
• Collaborator: (none)
• Enrollment: 18
• Arm: 1
• Duration (Months): 22

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hereditary Fructose Intolerance; Fructose Metabolism, Inborn Errors; Glucose Metabolism Disorders	Other: Test meal	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Are Heterozygous Carriers for Hereditary Fructose Intolerance Predisposed to Metabolic Disturbances When Exposed to Fructose?
• Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Jan 1, 2016
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: oral fructose load test meal calculated to provide 25% of basal energy requirement containing 13C-labeled fructose (0.35 g/kg), protein (0.21 g/kg) and lipid (0.22 g/kg).	Other: Test meal; Assessment of postprandial responses to a mixed meal containing fructose in carriers of one mutated ALDOB allele.

Outcome Measures

Primary Outcome Measures

1. Plasma glucose kinetics [-120 min before ingestion of a test meal to 360 min after ingestion of a test meal]

   Modelling of rate of glucose appearance after administration of a bolus of 6,6-2H2 glucose (bolus, 2 mg/kg and continuous infusion, 0.02 mg/kg/min) will be measured in fasted and fed conditions

Secondary Outcome Measures

1. Energy expenditure rate [120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal]

   Energy expenditure is measured by indirect calorimetry in fasted and fed conditions

2. Glucose oxidation rate [120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal]

   glucose oxidation is measured by indirect calorimetry in fasted and fed conditions

3. Plasma glucose concentration [-120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal]

   plasma glucose concentration measured by glucose oxidase

4. plasma insulin concentration [-120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal]

   Plasma insulin concentration measured by ELISA

5. Fructose oxidation [Every 30 min until 360 min after ingestion of a test meal]

   Fructose oxidation is measured from 13CO2 production

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• University of Lausanne

Investigators

• Study Director: Tappy Luc, MD, University of Lausanne

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Luc Tappy, MD, Professor, University of Lausanne
• ClinicalTrials.gov Identifier: NCT02979106
• Other Study ID Numbers: PB_2016-00289 (302/14)
• First Posted: Dec 1, 2016
• Last Update Posted: Jul 17, 2019
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Metabolism, Inborn Errors; Fructose Intolerance; Fructose Metabolism, Inborn Errors; Metabolic Diseases; Glucose Metabolism Disorders

Study Results

No Results Posted as of Jul 17, 2019