Curcumin Add-on Therapy for Induction of Remission in - PowerPoint PPT Presentation

Curcumin Add-on Therapy for Induction of Remission in Mild-to-Moderate Ulcerative Colitis: Results of a Multi-Center, Prospective, Randomized, Placebo-Controlled, Double- Blind Study Alon Lang 1* , Nir Salomon 1,2* , Uri Kopylov 1 , Adi Lahat 1 , Ofir Har-Noy 1 , Jessica Ching 3 , Pui Kuan Cheong 3 , Justin Wu 3 ,Benjamin Avidan 1 , Dorit Gamus 2 , John Kaimakliotis 4 , Rami Eliakim 1 , Siew Ng. 3* , Shomron Ben-Horin 1* Gastroenterology Department 1 & Complementary Medicine Service 2 , Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Israel, Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong 3 , Central IBD clinic, Nicosia, Cyprus 4 .

Curcumin Add-on Therapy for Induction of Remission in Mild-to-Moderate Ulcerative Colitis: Results of a Multi-Center, Prospective, Randomized, Placebo-Controlled, Double-Blind Study

Where are we going? • “Assessing the toolbox” • Screening for potential therapeutic agents 1 • “Find the role” • Establish a well-defined approach 2 • “Put to the test” • Well-designed, randomized, controlled trials 3

Curcumin A New Direction? • Curcumin is an active phyto- chemical compound derived from Rhizoma Curcuma Longa. • Researched areas: – Neurodegenerative diseases – Athritis – Cancer – Inflammatory diseases

Mechanism in animal models of IBD Suppresses NF-B Alters Expression of Cytokine Activity in Colonic Mucosa Genes Reduces CD4 T cells infiltration into lamina propria Sugimoto K. GASTROENTEROLOGY 2002;123:1912–1922 Uno K., GASTROENTEROLOGY 2006;131:497–509

Preliminary in-vitro experiments: CD4 Proliferation Inhibition of CD4 T cell Proliferation by Curcumin Curcumin 10uM Medium Curcumin 2.5uM 44.98 % 63.54% 83.72% Proliferation Proliferation Proliferation

Preliminary in-vitro experiments: Cytokine Suppression Inhibition of Monocyte secretion of TNF-alpha & IL-8 by Curcumin

Curcumin, but not mesalamine, inhibits activated T-cells: Implications for combo curcumin-mesalamine therapy T3 + 5ASA 0.5mM T3 + 5ASA 2mM T3 + Curcumin 2.5uM+5asa0.5mM T3 + Curcumin 2.5uM+5asa 2mM Salomon, N. Gastroenterology & Hepatology, 2012.

Third Line ~10% Unresponsive Disease Second Line Treatment Moderate-Severe Disease 20-30% Corticosteroids Purine analogues Anti-TNFs 60-70% First Line Treatment Mild-Moderate Disease/Remission 5 Amino-salicylic acid (5ASA) Oral/Topical

97 Patients 47 patients excluded: Trial Flow screened -31 not meeting inclusion criteria Chart -7 entered remission after topical 5ASA optimization -5 had normal sigmoidoscopy showing inactive disease -4 tested positive for C. diff 50 patients randomized 24 patients allocated 26 patients allocated to and received to receive curcumin placebo 1 patient was 1 lost to follow-up hospitalized before 1 withdrew consent initiation of drug 26 patients included 24 patients included in in ITT analysis ITT analysis 25 patients included 22 patients included in in PP analysis PP analysis

Results: Clinical Response and Remission P<0.001 P=0.01

Results: Endoscopic Response and Remission Endoscopic image showing marked erythema, loss of vascular pattern, tissue friability

Results: Endoscopic Response and Remission Same patient after 4 weeks of curcumin add-on therapy. Image showing inactive disease with nearly complete mucosal healing.

Third Line Unresponsive Disease Second Line Treatment Moderate-Severe Disease “Optimized” First Line Treatment First Line Treatment Mild-Moderate Disease/ Disease Remission 5ASA compounds (oral/topical) Curcumin Add-on Therapy + + Curcumin Add-on Therapy 5ASA compounds (oral/topical) and/or immuno-modulators