Background:
Focal segmental glomerulosclerosis (FSGS) is a disease that causes scarring in parts of the kidneys that filter waste. This can lead to protein loss in the urine, which can worsen kidney function. The kidneys may fail over time, and dialysis or a kidney transplant may be needed. Other treatments for this disease do not always work and often have adverse effects. Better treatments for FSGS are needed.
Objective:
To test a study drug (ManNAc) in people with FSGS.
Eligibility:
People aged 18 years and older with FSGS.
Design:
Participants will have 5 to 6 clinic visits over 14 weeks. Two of the visits will require overnight stays for 2 or 3 nights.
ManNAc is a white powder that comes in a sachet. It is dissolved in water and taken twice a day by mouth. Participants will take their first dose at the clinic. They will learn how to store ManNAc and prepare each dose. They will record their doses in a diary. They will also write down any adverse effects or troubles they have using the drug at home.
During clinic visits, participants will have physical exams with blood and urine tests. They will complete questionnaires about their health, sleep habits, and fatigue symptoms.
During overnight visits, participants will also have 24-hour urine collection.
A study team member will call participants 1 week after the first dose to check on their health. Follow-up phone calls will then be every 2 weeks after each clinic visit.
Participants may meet with a dietitian to discuss nutrition while taking the ManNAc.
Participants may choose to have genetic tests.
Prior kidney biopsy demonstrating FSGS obtained within 10 years prior to the screening visit.
Age >=18 years weighing more than 50 kg.
If the patient is on immunosuppressive therapy (e.g., prednisone, cyclosporine, tacrolimus or mycophenolate mofetil) he/she should be on these medications for at least 3 months prior to study evaluation and should be on a stable dose of the medication for at least 4 weeks before start of trial, with no plans to alter the regimen during 12 weeks of study period, except to stabilize levels and/or for any safety concerns.
Subjects will be allowed to continue with standard of care (SOC) non-immunosuppressant antiproteinuric agents to include RAAS inhibitors, mineralocorticoid antagonists (MRA), sodium-glucose co-transporter-2 inhibitors (SGLT2i), non-dihydropyridine calcium channel blockers (NDHP-CCBs), and glucagon-like peptide-1 (GLP-1) receptor agonists, in addition to other SOC adjuvant therapies such as diuretics, if they are able to maintain a stable dose throughout the trial. Subjects and their primary nephrologists will be encouraged to optimize their SOC treatments as much as possible prior to trial commencement. Subjects must be on a stable dose for at least 4 weeks before start of trial. Subjects should attempt to keep stable doses of both immunosuppressants and anti-proteinuric drugs throughout trial duration, to avoid confounding effects. Patients not receiving any of these SOC agents either due to allergy or intolerance will still be eligible.
Individuals who are unwilling or unable to provide informed consent.
Individual presenting for initial therapy of uncontrolled nephrotic syndrome which we define as proteinuria as measured by spot urine protein:creatinine ratio >3g/g or 24-hour urine protein excretion of >3.5g/day with symptomatic peripheral edema or pulmonary edema, hypoalbuminemia (serum albumin <3.0g/dl), electrolyte disturbances (related or unrelated to medical therapy), and/or active thromboembolism (initiated on systemic anticoagulation in the last 3 months). The rationale for this criterion is that patient presenting for initial therapy for uncontrolled nephrotic syndrome may need to be initiated on various medications including immunosuppressives as well as non-immunosuppressive drugs which can significantly change the level of proteinuria. Additionally, fluid shifts due to diuretic use for treating edema can alter GFR which could confound the pharmacokinetics and pharmacodymanics of the investigational drug.
Individuals who acutely require optimization of volume status with intravenous diuretics to control volume overload, as this may result in fluid shifts between the intravascular space and the remainder of extracellular fluid volume. This might alter drug pharmacokinetics and pharmacodynamics as mentioned above in # 2.
Individuals with a psychiatric illness or neurological disease that in the judgement of the investigators would interfere with the ability to adhere with the requirements of this protocol. This includes, but is not limited to, uncontrolled/untreated psychotic depression, bipolar disorder, schizophrenia, substance abuse or dependence, antisocial personality disorder, panic disorder, or behavioral problems, which might interfere with effective communication.