- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03545568
Sialic Acid Supplementation in N-Acetylneuraminic Acid Synthase (NANS) Deficiency
Sialic Acid Supplementation in NANS Deficiency: An Open-label, Proof of Concept, Two-centers Study
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Reggio Emilia, Italy, 42123
- Struttura Semplice Dipartimentale di Genetica Clinica
-
-
-
-
Vaud
-
Lausanne, Vaud, Switzerland, 1011
- Lausanne University Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Experimental: sialic acid
|
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
-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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
-30 min before Neu5Ac ingestion at day 2 to 4. With no Neu5Ac supplementation at day 5
|
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
|
-30 min before Neu5Ac ingestion at day 2 to 4. With no Neu5Ac supplementation at day 5
|
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
|
-30 min before Neu5Ac ingestion at day 2 to 4. With no Neu5Ac supplementation at day 5
|
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.
|
1x/day from day 1 to day 5 (end of the study)
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2018-00284
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on N-Acetylneuraminic Acid Storage Disease
-
AlexionRecruitingWolman Disease | Cholesterol Ester Storage Disease | Lysosomal Acid Lipase Deficiency | Acid Cholesteryl Ester Hydrolase Deficiency, Type 2 | Acid Lipase Deficiency | LIPA Deficiency | LAL-DeficiencyFrance, Belgium, United States, Spain, Germany, Greece, Israel, Italy, Slovenia, United Kingdom, Brazil, Canada, Denmark, Australia, Croatia, Czechia, Ireland, Mexico, Netherlands, Poland, Portugal, Saudi Arabia
-
AlexionCompletedWolman Disease | Lysosomal Acid Lipase DeficiencyUnited States, Canada, United Kingdom, Italy, France
-
Alexion PharmaceuticalsCompletedLysosomal Acid Lipase Deficiency | Cholesterol Ester Storage Disease(CESD)United States, United Kingdom, France, Canada, Czech Republic, Italy, Poland, Switzerland
-
Spark TherapeuticsActive, not recruitingLysosomal Storage Diseases | Glycogen Storage Disease Type II | Glycogen Storage Disease Type 2 | Pompe Disease (Late-onset) | Pompe Disease | LOPD | Acid Maltase DeficiencyUnited States, Canada, Netherlands, France, Denmark, Germany, Italy, United Kingdom
-
Spark TherapeuticsCompletedLysosomal Storage Diseases | Glycogen Storage Disease Type 2 | Pompe Disease (Late-onset) | Pompe Disease | LOPD | Acid Maltase DeficiencyUnited States, Italy, United Kingdom, Netherlands, France, Germany
-
CENTOGENE GmbH RostockWithdrawnCholesterol Ester Storage Disease | Acid Lipase Deficiency | Acid Cholesteryl Ester Hydrolase Deficiency, Wolman TypeGermany, India, Sri Lanka
-
Enzyvant Therapeutics GmBHCompletedFarber Disease | Farber's Disease | Farber Lipogranulomatosis | Acid Ceramidase Deficiency | Ceramidase Deficiency | N-Laurylsphingosine Deacylase Deficiency | ASAH1 MutationUnited States, Egypt, Canada, Italy, Turkey, Argentina, Germany, India, Sweden
-
Genzyme, a Sanofi CompanyCompletedPompe Disease | Glycogen Storage Disease Type II (GSD II) | Acid Maltase DeficiencyUnited States, Belgium, Denmark, France, Germany, Netherlands, United Kingdom
-
Hospices Civils de LyonUnknownLiver Post-transplant PatientsFrance
-
Genzyme, a Sanofi CompanyCompletedGlycogen Storage Disease Type II | Acid Maltase Deficiency Disease | Glycogenosis 2 | Pompe DiseaseUnited States
Clinical Trials on Neu5Ac supplementation
-
Université de SherbrookeUnknownSystolic Heart Failure | Sub-clinical HypothyroidismCanada
-
Maastricht University Medical CenterBioActor B.V.Recruiting
-
University of Missouri-ColumbiaAlmond Board of CaliforniaRecruiting
-
Charite University, Berlin, GermanyFreie Universität Berlin, Institute of Biology/Genetic, Berlin,Germany; Karl-Franzens-Universität...CompletedSubjective Cognitive DeclineGermany
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI)CompletedEsophagitis | Mucositis | Malignant NeoplasmUnited States
-
University of Alabama at BirminghamChildren's Health System, AlabamaActive, not recruitingPremature InfantUnited States
-
Seoul St. Mary's HospitalCompletedProtein-Energy MalnutritionKorea, Republic of
-
University of LeipzigCompleted
-
Assistance Publique - Hôpitaux de ParisCompleted
-
University of TaipeiCompletedAnthropometry | Cardiorespiratory Fitness | MetabolismTaiwan