Uncontrolled, Open Label, Pilot and Feasibility Study of Niacinamide in Polycystic Kidney Disease

Study Overview
=================
Brief Summary
-----------------
The goal of this pilot study is to evaluate the feasibility of administering niacinamide to patients with autosomal dominant polycystic kidney disease, to develop methods to assess the biological efficacy of niacinamide, and to perform a preliminary exploration of its clinical effect on kidney cyst growth and kidney function.

Detailed Description
-----------------
Niacinamide is a form of vitamin B3. Vitamin B3 is found in many foods including yeast, meat, fish, milk, eggs, green vegetables, beans, and cereal grains. Recent studies in mice have shown that niacinamide, at high doses, may slow kidney cyst growth from polycystic kidney disease (PKD). By doing this study, the researchers will determine if a larger, long-term study to test whether niacinamide slows progression of PKD is justified.

Official Title
-----------------
Uncontrolled, Open Label, Pilot and Feasibility Study of Niacinamide in Polycystic Kidney Disease

Conditions
-----------------
Polycystic Kidney Disease

Intervention / Treatment
-----------------
* Dietary Supplement: Niacinamide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Confirmed diagnosis of autosomal dominant polycystic kidney disease eGFR > 90ml/min/1.73m2 as determined from the serum creatinine by the CKD-EPI equation Ability to give informed consent in English 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 30 days prior to screening Partial or total nephrectomy or renal cyst reduction (including aspiration) done <1 year ago Cardiac pacemaker Presence of magnetic resonance-incompatible metallic clips (e.g. clipped cerebral aneurysm) Body weight >159 kg (350 lbs) or untreatable claustrophobia

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Niacinamide<br>All subjects in this study will take niacinamide at a dose of 30 mg per kilogram of body weight by mouth daily, in two divided daily doses, for 12 months. | Dietary Supplement: Niacinamide<br> <br> * Other names: Vitamin B3;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sirtuin deacetylase activity | Assessed by the level of post-translational modifications of two intracellular markers (1. Acetylated and total p53 protein concentrations, 2. Phosphorylated and total retinoblastoma protein (Rb)) | Change from Baseline to 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sirtuin deacetylase activity | Assessed by the level of post-translational modifications of two intracellular markers (1. Acetylated and total p53 protein concentrations, 2. Phosphorylated and total retinoblastoma protein (Rb)) | Change from Baseline to 6 Months | 
| Estimated Glomerular Filtration Rate (eGFR) | Measurements at each visit using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation | 12 Months | 
| Height-adjusted total kidney volumes (htTKV) | Measurements will be taken from MRI images, and the annual percent change in htTKV will be compared to historical values reported in a separate study of a similar study population. | Change from Baseline to 12 Months | 
| Biomarker levels | Aliquots of the urine samples from visits to be tested for a panel of biomarkers related to cyst growth compared to baseline levels. | 12 Months | 
| Subject pain | Subject feelings collected via abbreviated pain questionnaire. Questionnaire will be used to calculate pain score. | Change from Baseline to 12 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PKD, niacinamide, Vitamin B3, Vitamin B