Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Fructose Supplementation in Carriers for Hereditary Fructose Intolerance

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03545581
Recruitment Status : Completed
First Posted : June 4, 2018
Last Update Posted : April 22, 2019
Sponsor:
Collaborator:
University of Liege
Information provided by (Responsible Party):
Christel Tran, University of Lausanne

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.

Condition or disease Intervention/treatment Phase
Hereditary Fructose Intolerance Other: Experimental diet Fru rich diet Other: Experimental low Fru diet Not Applicable

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Metabolic Effects of Short-term Dietary Supplementation With Fructose in Carriers for Hereditary Fructose Intolerance
Actual Study Start Date : May 1, 2018
Actual Primary Completion Date : December 1, 2018
Actual Study Completion Date : April 1, 2019


Arm Intervention/treatment
Experimental diet Fru rich diet
Enriched fructose diet from day 1 to day 7.
Other: 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)

Experimental low Fru diet
Low fructose diet from day 1 to day 7.
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)




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03545581


Locations
Layout table for location information
Belgium
Guillaume Debray
Liège, Belgium
Sponsors and Collaborators
University of Lausanne
University of Liege

Layout table for additonal information
Responsible Party: Christel Tran, Principal Investigator, University of Lausanne
ClinicalTrials.gov Identifier: NCT03545581     History of Changes
Other Study ID Numbers: 2016-00289
First Posted: June 4, 2018    Key Record Dates
Last Update Posted: April 22, 2019
Last Verified: April 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Christel Tran, University of Lausanne:
Fructose
Uric acid
Glucose homeostasis
Additional relevant MeSH terms:
Layout table for MeSH terms
Fructose Intolerance
Fructose Metabolism, Inborn Errors
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases