Mutation in the key enzyme of sialic acid biosynthesis causes severe glomerular proteinuria and is rescued by N-acetylmannosamine.
Belinda Galeano, Riko Klootwijk, Irini Manoli...
https://pubmed.ncbi.nlm.nih.gov/17549255Actively Recruiting
Phase 2
Age: 18Years - 115Years
All Genders
ID06664814
An Open-Label Phase 2 Study of N-Acetyl-D-Mannosamine (ManNAc) in Subjects With Primary Focal Segmental Glomerulosclerosis
Led by National Human Genome Research Institute (NHGRI) · Updated on 2026-06-08
30
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Focal segmental glomerulosclerosis (FSGS) is a kidney disease that causes scarring in filtering areas, leading to protein loss in urine and declining kidney function. This condition may progress to kidney failure requiring dialysis or transplant. Current treatments often have limited success and side effects, so new options like the study drug ManNAc are being tested in people with FSGS aged 18 and older. This open-label Phase 2 study evaluates ManNAc taken as a 2,000 mg oral dose twice daily for 12 weeks in 15 participants with primary FSGS. ManNAc is a powder dissolved in water and taken by mouth. Participants will have 5 to 6 clinic visits over 14 weeks, including two overnight stays for 2 or 3 nights with 24-hour urine collection. The study will assess ManNAc's safety, tolerability, effects on proteinuria, pharmacokinetics, and its impact on kidney function and symptoms. Participants will undergo physical exams, blood and urine tests, questionnaires on health, sleep, and fatigue, and may meet with a dietitian. They will keep diaries of medication doses and any side effects. Follow-up calls will occur every two weeks after visits. Some may opt for genetic testing. The main outcomes measured include proteinuria reduction and safety over 12 weeks, with additional assessments of kidney function and patient-reported outcomes.
CONDITIONS
Brief Title
An Open-Label Phase 2 Study of N-Acetyl-D-Mannosamine (ManNAc) in Subjects With Primary Focal Segmental Glomerulosclerosis
Who Can Participate
Age: 18Years - 115Years
All Genders
Eligibility Criteria
You may qualify if you...
- Prior kidney biopsy confirming FSGS within 10 years before screening.
- Age 18 years or older and weighing more than 50 kg.
- Stable immunosuppressive therapy for at least 3 months and no dose changes for 4 weeks before trial start.
- Stable doses of standard non-immunosuppressive antiproteinuric agents for at least 4 weeks before trial.
- Spot urine protein/creatinine ratio of 2 g/g or more on three tests plus 24-hour urine protein of 2 g/day or more.
- Estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m² or higher.
- Willingness to use effective birth control if of reproductive potential or have had permanent birth control.
- Signed informed consent and willingness to comply with study procedures including diaries and visits.
You will not qualify if you...
- Unable or unwilling to provide informed consent.
- Initial therapy for uncontrolled nephrotic syndrome with high proteinuria and symptoms like edema or electrolyte problems.
- Need for intravenous diuretics for volume overload.
- Psychiatric or neurological illness interfering with study adherence.
- Vulnerable individuals with impaired cognition or incarceration.
- Kidney biopsy showing other pathology besides FSGS or over 50% interstitial fibrosis and tubular atrophy.
- Uncontrolled hypertension above 140/90 mmHg.
- Active infections including HIV, Hepatitis B or C, or others as determined.
- History of significant liver disease or abnormal liver tests.
- Hypertriglyceridemia over 500 mg/dL.
- Recent malignancy within 5 years or active therapy.
- History of diabetes mellitus.
- Hematological or cardiac conditions associated with FSGS.
- Use of medications linked to FSGS within 6 months.
- Pregnancy, breastfeeding, or refusal of birth control.
- Recent use of investigational drugs or ManNAc-related supplements.
- Previous organ or stem cell transplantation.
- Conditions increasing risk for adverse events or confounding results.
- Need for systemic immunosuppressive therapy for non-kidney reasons.
- Recent use of rituximab, cyclophosphamide, or plasmapheresis.
- Active alcohol or substance abuse within 2 years.
- Collapsing FSGS variant.
- Clinical history suggesting post-adaptive FSGS or obesity with BMI over 40 kg/m².
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - 12 weeks
Participants take ManNAc 2,000 mg orally twice daily for 12 weeks to evaluate the safety and effectiveness of the drug in reducing proteinuria associated with primary focal segmental glomerulosclerosis (FSGS).
Regular visits for assessments during 12 weeks
Trial Site Locations
Total: 1 location
1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Actively Recruiting
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Research Team
M
Marjan Huizing, Ph.D.
W
William A Gahl, M.D.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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Published Research Related To This Trial
In vivo enzymatic removal of alpha 2-->6-linked sialic acid from the glomerular filtration barrier results in podocyte charge alteration and glomerular injury.
H Gelberg, L Healy, H Whiteley...
https://pubmed.ncbi.nlm.nih.gov/8642786Rationale and Design for a Phase 1 Study of N-Acetylmannosamine for Primary Glomerular Diseases.
Marjan Huizing, Tal Yardeni, Federico Fuentes...
https://pubmed.ncbi.nlm.nih.gov/31701055Glycoprotein hyposialylation gives rise to a nephrotic-like syndrome that is prevented by sialic acid administration in GNE V572L point-mutant mice.
Mitutoshi Ito, Kazushi Sugihara, Tomoya Asaka...
https://pubmed.ncbi.nlm.nih.gov/22253810The Gne M712T mouse as a model for human glomerulopathy.
Sravan Kakani, Tal Yardeni, Justin Poling...
https://pubmed.ncbi.nlm.nih.gov/22322304Oral monosaccharide therapies to reverse renal and muscle hyposialylation in a mouse model of GNE myopathy.
Terren K Niethamer, Tal Yardeni, Petcharat Leoyklang...
https://pubmed.ncbi.nlm.nih.gov/23122659Sialic acid supplementation ameliorates puromycin aminonucleoside nephrosis in rats.
Izabella Z A Pawluczyk, Maryam G Najafabadi, Jeremy R Brown...
https://pubmed.ncbi.nlm.nih.gov/26121320An Outcomes-Based Definition of Proteinuria Remission in Focal Segmental Glomerulosclerosis.
Jonathan P Troost, Howard Trachtman, Patrick H Nachman...
https://pubmed.ncbi.nlm.nih.gov/29167190The longitudinal relationship between patient-reported outcomes and clinical characteristics among patients with focal segmental glomerulosclerosis in the Nephrotic Syndrome Study Network.
Jonathan P Troost, Anne Waldo, Noelle E Carlozzi...
https://pubmed.ncbi.nlm.nih.gov/32905199Validity and reliability of the Patient-Reported Outcomes Measurement Information System (PROMIS®) using computerized adaptive testing in patients with advanced chronic kidney disease.
Esmee M van der Willik, Fenna van Breda, Brigit C van Jaarsveld...
https://pubmed.ncbi.nlm.nih.gov/35913734