Pilot Study of Niacinamide in Polycystic Kidney Disease (NIAC-PKD2)

Study Overview
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Brief Summary
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The purpose of this study is to observe the effects of niacinamide on markers of kidney injury, inflammation, kidney cyst growth and kidney function.

Detailed Description
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Polycystic Kidney Disease (PKD) is a genetic disease that affects about 1 in 500 people worldwide. It can lead to kidney failure which can lead to death. PKD causes the development of kidney cysts (fluid-filled balloons), which cause worsening kidney function. It is common for people with PKD to also have blood in the urine, kidney pain, high blood pressure, kidney stones, kidney infections, and cysts in the brain or other parts of the body. There is currently no treatment known to stop cyst growth or a cure for the disease. Participants in this study will be randomly assigned to one of two groups: niacinamide or placebo. Participants have an equal chance of being assigned to either of the groups. For people that qualify and decide to participate in this study, they will be asked to make five visits to the study clinic and complete two study related phone calls over the course of 12 months.

Official Title
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Randomized, Controlled Pilot Study of Niacinamide in Polycystic Kidney Disease

Conditions
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Polycystic Kidney Disease

Intervention / Treatment
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* Dietary Supplement: Niacinamide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of autosomal dominant polycystic kidney disease (ADPKD). Estimated glomerular filtration rate (eGFR) > 50 ml/min/1.73m2 as determined from the serum creatinine by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation Provide Informed consent Exclusion Criteria: History of liver disease or abnormal liver function test Heavy alcohol intake Chronic diarrhea or malabsorption syndrome Thrombocytopenia Hypophosphatemia Pregnancy or lactation or plan to become pregnant during the study Treatment with anti-epileptic drugs Treatment with tolvaptan, current or within 2 months prior to screening Participation in another interventional trial currently or within 2 months prior to screening. Exclusions specific to magnetic resonance (MR) imaging acquisition and measurement: Partial or total nephrectomy or renal cyst reduction (including aspiration) done <1 year ago Cardiac pacemaker. Presence of MR incompatible metallic clips (e.g. clipped cerebral aneurysm) Body weight >159 kg (350 lbs) or untreatable claustrophobia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Niacinamide<br>Participants will be asked to take niacinamide at a dose of 30 mg/kg/d orally. | Dietary Supplement: Niacinamide<br> <br> * Other names: Vitamin B3;|
| Placebo Comparator: Placebo<br>Participants will be asked to take a placebo pill at a dose of 30 mg/kg/d orally. | Other: Placebo<br>* Placebo pill that matches niacinamide pill is size, shape and color<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in acetylated/total p53 ratio measured by ELISA in peripheral blood mononuclear cells (PBMC) | Sirtuin 1 deacetylates p53 protein, and niacinamide inhibits sirtuin 1. So an increase in acetylated/total p53 ratio in PBMC will be used as a marker of biological efficacy. | Change from Baseline to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in height-adjusted total kidney volume | Measured by MRI | Change from Baseline to Month 12 | 
| Change in score on pain questionnaire | PKD-9 Pain Questionnaire: Range of scores from 13 (no pain or symptoms) to 70 (very severe symptoms almost every day) | Change from Baseline to Month 12 | 
| Change in urinary concentration of MCP-1 |  | Change from Baseline to Month 12 | 
| Change in estimated GFR | Determined from serum creatinine concentrations using CKD-Epi equation | Change from Baseline to Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PKD, Kidney disease, Vitamin B3