Back to results

Metabolic Consequences of Heterozygous Hereditary Fructose Intolerance

Primary Purpose

Hereditary Fructose Intolerance, Fructose Metabolism, Inborn Errors, Glucose Metabolism Disorders

Status

Completed

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

Test meal

About this trial

This is an interventional basic science trial for Hereditary Fructose Intolerance

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

oral fructose load

Arm Description

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).

Outcomes

Primary Outcome Measures

Plasma glucose kinetics

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

Energy expenditure rate

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

Glucose oxidation rate

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

Plasma glucose concentration

plasma glucose concentration measured by glucose oxidase

plasma insulin concentration

Plasma insulin concentration measured by ELISA

Fructose oxidation

Fructose oxidation is measured from 13CO2 production

Full Information

NCT ID

NCT02979106

First Posted

November 14, 2016

Last Updated

July 15, 2019

Sponsor

University of Lausanne

1. Study Identification

Unique Protocol Identification Number

NCT02979106

Brief Title

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

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Completed

Study Start Date

January 2015 (undefined)

Primary Completion Date

January 2016 (Actual)

Study Completion Date

November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Lausanne

4. Oversight

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hereditary Fructose Intolerance, Fructose Metabolism, Inborn Errors, Glucose Metabolism Disorders

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

oral fructose load

Arm Type

Experimental

Arm Description

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).

Intervention Type

Other

Intervention Name(s)

Test meal

Intervention Description

Assessment of postprandial responses to a mixed meal containing fructose in carriers of one mutated ALDOB allele.

Primary Outcome Measure Information:

Title

Plasma glucose kinetics

Description

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

Time Frame

-120 min before ingestion of a test meal to 360 min after ingestion of a test meal

Secondary Outcome Measure Information:

Title

Energy expenditure rate

Description

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

Time Frame

120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal

Title

Glucose oxidation rate

Description

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

Time Frame

120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal

Title

Plasma glucose concentration

Description

plasma glucose concentration measured by glucose oxidase

Time Frame

-120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal

Title

plasma insulin concentration

Description

Plasma insulin concentration measured by ELISA

Time Frame

-120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal

Title

Fructose oxidation

Description

Fructose oxidation is measured from 13CO2 production

Time Frame

Every 30 min until 360 min after ingestion of a test meal

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tappy Luc, MD

Organizational Affiliation

University of Lausanne

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

29955837

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.

Results Reference

derived

Learn more about this trial

Metabolic Consequences of Heterozygous Hereditary Fructose Intolerance

We'll reach out to this number within 24 hrs