Ignite Creation Date:
2025-12-24 @ 5:37 PM
Ignite Modification Date:
2026-02-28 @ 10:37 AM
Study NCT ID:
NCT03545568
Status:
COMPLETED
Last Update Posted:
2018-11-14
First Post:
2018-05-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Sialic Acid Supplementation in N-Acetylneuraminic Acid Synthase (NANS) Deficiency
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'C535525', 'term': 'N-Acetylneuraminic acid storage disease'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Open label individual patient clinical trial study of small sample size'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 10}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-05-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-05', 'completionDateStruct': {'date': '2018-10-15', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-11-13', 'studyFirstSubmitDate': '2018-05-08', 'studyFirstSubmitQcDate': '2018-05-22', 'lastUpdatePostDateStruct': {'date': '2018-11-14', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-06-04', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2018-10-15', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Metabolite concentration', 'timeFrame': '-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', 'description': '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'}], 'secondaryOutcomes': [{'measure': 'Urine and plasma concentrations of N-acetyl mannosamine (ManNAc)', 'timeFrame': '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', 'description': 'Change in ManNAc concentration from baseline and after exogenous sialic acid supplementation'}, {'measure': 'Urine and plasma concentrations of free sialic acid', 'timeFrame': '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', 'description': 'Change in free sialic acid concentration from baseline and after exogenous sialic acid supplementation'}, {'measure': 'Urine and plasma concentrations of total sialic acid', 'timeFrame': '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', 'description': 'Change in total sialic acid concentration from baseline and after exogenous sialic acid supplementation'}, {'measure': 'Urine and plasma concentrations of N-Acetyl-D neuraminic acid (Neu5Ac)', 'timeFrame': '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', 'description': 'Change in Neu5Ac concentration from baseline and after exogenous sialic acid supplementation'}, {'measure': 'Urine and plasma metabolomic profile', 'timeFrame': '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', 'description': 'Change in metabolomic profile from baseline and after exogenous sialic acid supplementation'}, {'measure': 'Blood pressure in mmHg', 'timeFrame': '-30 min before Neu5Ac ingestion at day 2 to 4. With no Neu5Ac supplementation at day 5', 'description': 'Measure of blood pressure (mmHg) supplementation'}, {'measure': 'Heart beat per minute (BPM)', 'timeFrame': '-30 min before Neu5Ac ingestion at day 2 to 4. With no Neu5Ac supplementation at day 5', 'description': 'Measure of heart BPM at baseline and after exogenous sialic acid supplementation'}, {'measure': 'Body weight (kg)', 'timeFrame': '-30 min before Neu5Ac ingestion at day 2 to 4. With no Neu5Ac supplementation at day 5', 'description': 'Measure of body weight at baseline and after exogenous sialic acid supplementation'}, {'measure': 'Dietary parameters', 'timeFrame': '1x/day from day 1 to day 5 (end of the study)', 'description': 'A self-reporting daily dietetic diary will be recorded for each participant.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Sialic acid', 'Monosaccharide'], 'conditions': ['N-Acetylneuraminic Acid Storage Disease']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nThe 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '60 Years', 'minimumAge': '1 Year', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria for controls:\n\n* 4 healthy adults aged 18 to 60 years (inclusion in Switzerland)\n\nInclusion Criteria for subjects with NANS deficiency:\n\n* 4 adults aged 18 to 60 years with genetically proven NANS deficiency (inclusion in Italy)\n* 2 children aged 1 to 18 years with genetically proven NANS deficiency (inclusion in Switzerland)\n\nExclusion Criteria for controls:\n\n* Medication, Restrictive diet (e.g. lactose free diet), obesity or other co-morbidities (e.g. neurological disease, developmental delay)\n\nNo exclusion Criteria for subjects'}, 'identificationModule': {'nctId': 'NCT03545568', 'briefTitle': 'Sialic Acid Supplementation in N-Acetylneuraminic Acid Synthase (NANS) Deficiency', 'organization': {'class': 'OTHER', 'fullName': 'University of Lausanne'}, 'officialTitle': 'Sialic Acid Supplementation in NANS Deficiency: An Open-label, Proof of Concept, Two-centers Study', 'orgStudyIdInfo': {'id': '2018-00284'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'OTHER', 'label': 'Experimental: sialic acid', 'interventionNames': ['Other: Neu5Ac supplementation']}], 'interventions': [{'name': 'Neu5Ac supplementation', 'type': 'OTHER', 'description': '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', 'armGroupLabels': ['Experimental: sialic acid']}]}, 'contactsLocationsModule': {'locations': [{'zip': '42123', 'city': 'Reggio Emilia', 'country': 'Italy', 'facility': 'Struttura Semplice Dipartimentale di Genetica Clinica', 'geoPoint': {'lat': 44.69825, 'lon': 10.63125}}, {'zip': '1011', 'city': 'Lausanne', 'state': 'Canton of Vaud', 'country': 'Switzerland', 'facility': 'Lausanne University Hospital', 'geoPoint': {'lat': 46.516, 'lon': 6.63282}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Lausanne', 'class': 'OTHER'}, 'collaborators': [{'name': 'University of Modena and Reggio Emilia', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal investigator', 'investigatorFullName': 'Christel Tran', 'investigatorAffiliation': 'University of Lausanne'}}}}