We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 6 for:    NANS
Previous Study | Return to List | Next Study

Sialic Acid Supplementation in N-Acetylneuraminic Acid Synthase (NANS) Deficiency

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: NCT03545568
Recruitment Status : Completed
First Posted : June 4, 2018
Last Update Posted : November 14, 2018
Sponsor:
Collaborator:
University of Modena and Reggio Emilia
Information provided by (Responsible Party):
Christel Tran, University of Lausanne

Tracking Information
First Submitted Date  ICMJE May 8, 2018
First Posted Date  ICMJE June 4, 2018
Last Update Posted Date November 14, 2018
Actual Study Start Date  ICMJE May 1, 2018
Actual Primary Completion Date October 15, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 22, 2018)
Metabolite concentration [ Time Frame: -30 min before ingestion of Neu5Ac at day 2. 120 min, 240 min and 360 min after Neu5Ac ingestion at day 2. 120 min after neu5Ac ingestion at day 3-4. With no Neu5Ac supplementation at day 5 ]
The primary endpoint is the change of metabolite concentration after N-Acetyl-D neuraminic acid (Neu5Ac) supplementation from day 2 to day 4 and follow-up visit at day 5
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2018)
  • Urine and plasma concentrations of N-acetyl mannosamine (ManNAc) [ Time Frame: 30 min before ingestion of Neu5Ac at day 2. 120 min, 240 min and 360 min after Neu5Ac ingestion at day 2. 120 min after neu5Ac ingestion at day 3-4. With no Neu5Ac supplementation at day 5 ]
    Change in ManNAc concentration from baseline and after exogenous sialic acid supplementation
  • Urine and plasma concentrations of free sialic acid [ Time Frame: 30 min before ingestion of Neu5Ac at day 2. 120 min, 240 min and 360 min after Neu5Ac ingestion at day 2. 120 min after neu5Ac ingestion at day 3-4. With no Neu5Ac supplementation at day 5 ]
    Change in free sialic acid concentration from baseline and after exogenous sialic acid supplementation
  • Urine and plasma concentrations of total sialic acid [ Time Frame: 30 min before ingestion of Neu5Ac at day 2. 120 min, 240 min and 360 min after Neu5Ac ingestion at day 2. 120 min after neu5Ac ingestion at day 3-4. With no Neu5Ac supplementation at day 5 ]
    Change in total sialic acid concentration from baseline and after exogenous sialic acid supplementation
  • Urine and plasma concentrations of N-Acetyl-D neuraminic acid (Neu5Ac) [ Time Frame: 30 min before ingestion of Neu5Ac at day 2. 120 min, 240 min and 360 min after Neu5Ac ingestion at day 2. 120 min after neu5Ac ingestion at day 3-4. With no Neu5Ac supplementation at day 5 ]
    Change in Neu5Ac concentration from baseline and after exogenous sialic acid supplementation
  • Urine and plasma metabolomic profile [ Time Frame: 30 min before ingestion of Neu5Ac at day 2. 120 min, 240 min and 360 min after Neu5Ac ingestion at day 2. 120 min after neu5Ac ingestion at day 3-4. With no Neu5Ac supplementation at day 5 ]
    Change in metabolomic profile from baseline and after exogenous sialic acid supplementation
  • Blood pressure in mmHg [ Time Frame: -30 min before Neu5Ac ingestion at day 2 to 4. With no Neu5Ac supplementation at day 5 ]
    Measure of blood pressure (mmHg) supplementation
  • Heart beat per minute (BPM) [ Time Frame: -30 min before Neu5Ac ingestion at day 2 to 4. With no Neu5Ac supplementation at day 5 ]
    Measure of heart BPM at baseline and after exogenous sialic acid supplementation
  • Body weight (kg) [ Time Frame: -30 min before Neu5Ac ingestion at day 2 to 4. With no Neu5Ac supplementation at day 5 ]
    Measure of body weight at baseline and after exogenous sialic acid supplementation
  • Dietary parameters [ Time Frame: 1x/day from day 1 to day 5 (end of the study) ]
    A self-reporting daily dietetic diary will be recorded for each participant.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sialic Acid Supplementation in N-Acetylneuraminic Acid Synthase (NANS) Deficiency
Official Title  ICMJE Sialic Acid Supplementation in NANS Deficiency: An Open-label, Proof of Concept, Two-centers Study
Brief Summary This study is aimed at assessing the impact of short-term (3 days) exogenous sialic acid supplementation on endogenous biomarkers of sialic acid metabolism in NANS deficient patients.
Detailed Description

NANS deficiency is a genetic disorder presenting clinically with intellectual development disorder, skeletal dysplasia and dysmorphic features. It has recently been described in 9 patients (4 children and 5 adults). Biallelic mutations in the NANS (N-Acetylneuraminic acid synthase) gene cause a block in the endogenous synthesis of sialic acid and accumulation of the precursor, N-acetyl mannosamine (ManNAc). In a cell culture model, this block results in hyposialylation of glycoproteins and glycolipids. It seems likely that in human, this enzyme deficiency impairs the sialylation of glycolipids and glycoproteins, known to be essential for brain development. Exogenously added sialic acid partially rescued the phenotype of NANS-deficient zebra fish. Currently there is no approved treatment for patients with NANS deficiency. The investigators concluded that exogenous sialic acid supplementation might be useful for NANS patients. Given that sialic acid is found as both, a free sugar and in a bound form in standard nutrition as well as in high quantities in breast milk, it can be considered as a safe nutritional ingredient; this notion is fully supported by animal toxicity studies.

The use of sialic acid in NANS deficiency is in line with oral supplementation of specific sugars for treatment of other glycosylation and sialylation defects such as congenital disorders of glycosylation (CDG) and myopathy with mutation in the gene GNE. This novel monosaccharide therapy represents an opportunity to address fundamental biochemical questions about the relative contribution of endogenous and dietary sources on sialic acid metabolism and its potential role as a future therapy for NANS patients.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Open label individual patient clinical trial study of small sample size
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE N-Acetylneuraminic Acid Storage Disease
Intervention  ICMJE Other: Neu5Ac supplementation
Sialic acid as N-Acetyl-neuraminic acid dehydrate (Neu5Ac) 150 mg/kg/d (max 12g/d) in three doses orally in subjects with NANS deficiency compared to controls
Study Arms  ICMJE Experimental: sialic acid
Intervention: Other: Neu5Ac supplementation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 22, 2018)
10
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 15, 2018
Actual Primary Completion Date October 15, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria for controls:

  • 4 healthy adults aged 18 to 60 years (inclusion in Switzerland)

Inclusion Criteria for subjects with NANS deficiency:

  • 4 adults aged 18 to 60 years with genetically proven NANS deficiency (inclusion in Italy)
  • 2 children aged 1 to 18 years with genetically proven NANS deficiency (inclusion in Switzerland)

Exclusion Criteria for controls:

  • Medication, Restrictive diet (e.g. lactose free diet), obesity or other co-morbidities (e.g. neurological disease, developmental delay)

No exclusion Criteria for subjects

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 60 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03545568
Other Study ID Numbers  ICMJE 2018-00284
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Christel Tran, University of Lausanne
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Lausanne
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE University of Modena and Reggio Emilia
Investigators  ICMJE Not Provided
PRS Account University of Lausanne
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP