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 Lang1*, Nir Salomon1,2*, Uri Kopylov1 , Adi Lahat 1, Ofir Har-Noy1, Jessica Ching3 , Pui Kuan Cheong3 , Justin Wu 3 ,Benjamin Avidan1, Dorit Gamus2, John Kaimakliotis4, Rami Eliakim1, Siew Ng.3*, Shomron Ben-Horin1*

Gastroenterology Department1 & Complementary Medicine Service2, Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Israel, Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong3 , Central IBD clinic, Nicosia, Cyprus4.

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?

1

• “Assessing the toolbox”
• Screening for potential therapeutic agents

2

• “Find the role”
• Establish a well-defined approach

3

• “Put to the test”
• Well-designed, randomized, controlled trials

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 Activity in Colonic Mucosa Alters Expression of Cytokine 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

Medium

83.72% Proliferation

Curcumin 2.5uM

63.54% Proliferation

Curcumin 10uM

44.98% 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+5asa 2mM T3 + Curcumin 2.5uM+5asa0.5mM

Salomon, N. Gastroenterology & Hepatology, 2012.

Third Line Unresponsive Disease Second Line Treatment Moderate-Severe Disease

Corticosteroids Purine analogues Anti-TNFs

First Line Treatment Mild-Moderate Disease/Remission

5 Amino-salicylic acid (5ASA) Oral/Topical

20-30% 60-70% ~10%

97 Patients screened 47 patients excluded:

• 31 not meeting inclusion

criteria

• 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 to and received placebo 24 patients included in ITT analysis 22 patients included in PP analysis 1 lost to follow-up 1 withdrew consent 26 patients allocated to receive curcumin 26 patients included in ITT analysis 25 patients included in PP analysis 1 patient was hospitalized before initiation of drug

Trial Flow Chart

P=0.01 P<0.001

Results: Clinical Response and Remission

Endoscopic image showing marked erythema, loss of vascular pattern, tissue friability

Results: Endoscopic Response and Remission

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

First Line Treatment Mild-Moderate Disease/ Disease Remission Curcumin Add-on Therapy + 5ASA compounds (oral/topical) and/or immuno-modulators

“Optimized” First Line Treatment

5ASA compounds (oral/topical) + Curcumin Add-on Therapy