TY - JOUR
T1 - Biological Efficacy and Safety of Niacinamide in Patients With ADPKD
AU - El Ters, Mireille
AU - Zhou, Xia
AU - Lepping, Rebecca J.
AU - Lu, Pengcheng
AU - Karcher, Rainer T.
AU - Mahnken, Jonathan D.
AU - Brooks, William M.
AU - Winklhofer, Franz T.
AU - Li, Xiaogang
AU - Yu, Alan S.L.
N1 - Funding Information:
This study was supported by a pilot grant through the Frontiers Pilot and Collaborative Studies Funding Program funded by a National Institutes of Health (NIH) Clinical and Translational Science Award grant ( UL1 TR000001 , formerly UL1RR033179 ) awarded to the University of Kansas Medical Center , by the internal clinical pilot grant program of the KUMC Research Institute, by a Pilot and Feasibility Clinical Research Grants in Kidney or Urologic Diseases grant ( R21 DK104086 ), by the Kansas PKD Research and Translation Core Center ( P30 DK106912 ), and by the Kansas Institute of Precision Medicine ( P20 GM130423 ). The Hoglund Brain Imaging Center is supported by a generous gift from Forrest and Sally Hoglund and funding from NIH ( P30 DK106912 , S10 RR29577 , UL1 TR000001 ).
Publisher Copyright:
© 2020 International Society of Nephrology
PY - 2020/8
Y1 - 2020/8
N2 - Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst enlargement, leading to kidney failure. Sirtuin-1 is upregulated in ADPKD and accelerates disease progression by deacetylating p53. Niacinamide is a dietary supplement that inhibits sirtuins at high doses. Methods: We conducted an open-label, single-arm intervention trial (study 1, N = 10), and a randomized, double blinded, placebo-controlled trial (study 2, N = 36) to assess the biological activity and safety of niacinamide. Patients with ADPKD were given 30 mg/kg oral niacinamide or placebo, for 12 months. The primary endpoint was the ratio of acetylated p53 to total p53 protein in peripheral blood mononuclear cells (PBMCs). Results: There was no sustained effect of niacinamide on acetylated/total p53 in either study and no difference between placebo and niacinamide arms. There was no difference in the change in height-adjusted total kidney volume over 12 months between niacinamide and placebo. Niacinamide was generally well tolerated. The most common adverse effects were nausea, diarrhea, gastroesophageal reflux, headache, and acneiform rash but there was no difference in their incidence between niacinamide and placebo. Conclusions: In conclusion, niacinamide is safe and well-tolerated in patients with ADPKD. However, we were unable to detect a sustained inhibition of sirtuin activity over 12 months of treatment, and there was no signal to suggest a beneficial effect on any efficacy measure.
AB - Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst enlargement, leading to kidney failure. Sirtuin-1 is upregulated in ADPKD and accelerates disease progression by deacetylating p53. Niacinamide is a dietary supplement that inhibits sirtuins at high doses. Methods: We conducted an open-label, single-arm intervention trial (study 1, N = 10), and a randomized, double blinded, placebo-controlled trial (study 2, N = 36) to assess the biological activity and safety of niacinamide. Patients with ADPKD were given 30 mg/kg oral niacinamide or placebo, for 12 months. The primary endpoint was the ratio of acetylated p53 to total p53 protein in peripheral blood mononuclear cells (PBMCs). Results: There was no sustained effect of niacinamide on acetylated/total p53 in either study and no difference between placebo and niacinamide arms. There was no difference in the change in height-adjusted total kidney volume over 12 months between niacinamide and placebo. Niacinamide was generally well tolerated. The most common adverse effects were nausea, diarrhea, gastroesophageal reflux, headache, and acneiform rash but there was no difference in their incidence between niacinamide and placebo. Conclusions: In conclusion, niacinamide is safe and well-tolerated in patients with ADPKD. However, we were unable to detect a sustained inhibition of sirtuin activity over 12 months of treatment, and there was no signal to suggest a beneficial effect on any efficacy measure.
KW - clinical trial
KW - niacinamide
KW - p53
KW - polycystic kidney disease
KW - sirtuin
UR - http://www.scopus.com/inward/record.url?scp=85087807131&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85087807131&partnerID=8YFLogxK
U2 - 10.1016/j.ekir.2020.06.002
DO - 10.1016/j.ekir.2020.06.002
M3 - Article
AN - SCOPUS:85087807131
VL - 5
SP - 1271
EP - 1279
JO - Kidney International Reports
JF - Kidney International Reports
SN - 2468-0249
IS - 8
ER -