N-Acetylneuraminic Acid Storage DiseaseNCT03545568
Sialic Acid Supplementation in N-Acetylneuraminic Acid Synthase (NANS) Deficiency
A study testing Neu5Ac supplementation in people with N-Acetylneuraminic Acid Storage Disease, run by University of Lausanne at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- N-Acetylneuraminic Acid Storage Disease
- What is being tested?
- Neu5Ac supplementation
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 May 2018to 15 Oct 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 60 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 4 healthy adults aged 18 to 60 years (inclusion in Switzerland)
- 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)
Who cannot join
- Medication, Restrictive diet (e.g. lactose free diet), obesity or other co-morbidities (e.g. neurological disease, developmental delay)
- No exclusion Criteria for subjects
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Italy1 site
Struttura Semplice Dipartimentale di Genetica Clinica
Reggio Emilia, 42123
Switzerland1 site
Lausanne University Hospital
Lausanne, Canton of Vaud, 1011
About this study
Official title: Sialic Acid Supplementation in NANS Deficiency: An Open-label, Proof of Concept, Two-centers Study
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.
Read the 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.
- Conditions
- N-Acetylneuraminic Acid Storage Disease
- Being tested
- Neu5Ac supplementation
- Keywords
- Sialic acid, Monosaccharide
- Medical subject headings
- N-Acetylneuraminic acid storage disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neu5Ac supplementationOther
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 group | Role | What they receive |
|---|---|---|
| Experimental: sialic acid | Other | Not described Receives: Other: Neu5Ac supplementation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metabolite concentration
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
Measured: -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 outcomes (9)
Urine and plasma concentrations of N-acetyl mannosamine (ManNAc)
Change in ManNAc concentration from baseline and after exogenous sialic acid supplementation
Measured: 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
Change in free sialic acid concentration from baseline and after exogenous sialic acid supplementation
Measured: 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
Change in total sialic acid concentration from baseline and after exogenous sialic acid supplementation
Measured: 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)
Change in Neu5Ac concentration from baseline and after exogenous sialic acid supplementation
Measured: 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
Change in metabolomic profile from baseline and after exogenous sialic acid supplementation
Measured: 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
Measure of blood pressure (mmHg) supplementation
Measured: -30 min before Neu5Ac ingestion at day 2 to 4. With no Neu5Ac supplementation at day 5
Heart beat per minute (BPM)
Measure of heart BPM at baseline and after exogenous sialic acid supplementation
Measured: -30 min before Neu5Ac ingestion at day 2 to 4. With no Neu5Ac supplementation at day 5
Body weight (kg)
Measure of body weight at baseline and after exogenous sialic acid supplementation
Measured: -30 min before Neu5Ac ingestion at day 2 to 4. With no Neu5Ac supplementation at day 5
Dietary parameters
A self-reporting daily dietetic diary will be recorded for each participant.
Measured: 1x/day from day 1 to day 5 (end of the study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2018
- Study start1 May 2018
- Primary completion15 Oct 2018
- Study completion15 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for N-Acetylneuraminic Acid Storage DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open label individual patient clinical trial study of small sample size
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Lausanne
- Sponsor type
- University, hospital or other
- Collaborators
- University of Modena and Reggio Emilia
- Responsible party
- Principal investigator, Christel Tran, University of Lausanne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03545568
- Sponsor's protocol ID
- 2018-00284
- Other IDs
- 2018
- Status last verified
- May 2018
- First submitted
- 8 May 2018
- Last updated
- 14 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sialic Acid Supplementation in NANS Deficiency: An Open-label, Proof of Concept, Two-centers Study
- ClinicalTrials.gov ID
- NCT03545568
- Acronym / sponsor ID
- 2018-00284
- Conditions
- N-Acetylneuraminic Acid Storage Disease
- Keywords
- Sialic acid, Monosaccharide
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of LausanneUniversity, hospital or other
- Collaborators
- University of Modena and Reggio Emilia
- Study start
- 1 May 2018 (actual)
- Primary completion
- 15 Oct 2018 (actual)
- Study completion
- 15 Oct 2018 (actual)
- First posted
- 4 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label individual patient clinical trial study of small sample size
| Arm | Type | Receives |
|---|---|---|
| Experimental: sialic acid | Other | Other: Neu5Ac supplementation |
Who may qualify
- Ages
- 1 year to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 4 healthy adults aged 18 to 60 years (inclusion in Switzerland)
- 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)
Key exclusion criteria (2 listed)
- Medication, Restrictive diet (e.g. lactose free diet), obesity or other co-morbidities (e.g. neurological disease, developmental delay)
- No exclusion Criteria for subjects
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neu5Ac supplementationSialic 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 | Other | Experimental: sialic acid |
Primary outcome
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
9 secondary outcomes
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
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
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
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
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
Blood pressure in mmHg
Time frame: -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
Body weight (kg)
Time frame: -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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Neu5Ac supplementation in people with N-Acetylneuraminic Acid Storage Disease, run by University of Lausanne at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2018.