Saffron and Ulcerative Colitis

The Effect of Saffron in Patients With Ulcerative Colitis: A Randomized Double-blind Clinical Trial

IBD is a chronic disease with two major types of Crohn's Disease (CD) and Ulcerative Colitis (UC). Nowadays, synthetic drugs and monoclonal antibodies are the most common types of drugs used for IBD management. However, due to their side effects and the high relapse rate, many researchers are looking for plant-derived products to manage the disease. Saffron, Crocus sativus L., is widely used as spice and medicine with anti-obesity, anticonvulsant, anti-hyperlipidemic, anti-tumor, antioxidant, and anti-inflammatory properties. Besides, there is evidence of the favorable effects of saffron on the gut microbiome. The main aim of this proposal is to evaluate the effect of saffron as a complementary supplement or add-on therapy in combination with current therapeutic agents in patients with mild and moderate UC.

Study Overview

• Status: Not yet recruiting
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Saffron 100; Drug: Saffron 50; Drug: Placebo

Detailed Description

This study will be a parallel, randomized, double-blinded clinical trial assessing the efficacy of the saffron extract compared to placebo in patients with mild and moderate UC. Sixty eligible patients will be recruited and randomized into 6 groups to receive either saffron capsule or placebo. Randomization will be performed by an independent researcher (AAK) who is not directly involved in the trial and using software-generated random permuted blocks. Allocation concealment will be also conducted using sealed, opaque envelopes with consecutive numbering. The saffron and placebo will be provided free of charge by Sina Pajoohan Salamat co, Mashhad, Iran. The standard treatment will be administered to all patients as recommendations of the physicians.

Intervention

The intervention groups of study will be included:

1. Mild UC patients, receiving100 milligram (mg)/day saffron for 8 weeks (50 mg two times (BID)), n=10
2. Moderate UC patients, receiving100 mg/day saffron for 8 weeks (50 mg BID), n=10
3. Mild UC patients, receiving 50 mg/day saffron for 8 weeks (25 mg BID), n=10
4. Moderate UC patients, receiving 50 mg/day saffron for 8 weeks (25 mg BID), n=10
5. Mild UC patients, receiving 2 tablets of placebo for 8 weeks, n=10
6. Moderate UC patients, receiving 2 tablets of placebo for 8 weeks, n=10

Demographic and baseline characteristics will be recorded, and assessment of anthropometric and biochemical parameters, fecal calprotectin, inflammatory cytokines, stool microbiome, and its transcriptomic, and metabolomic, urine and saliva metabolomics, health-related quality of life (HRQoL), anxiety, and disease severity will be done at baseline and after 8 weeks. Fecal calprotectin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and disease severity will also be evaluated at 4th week. Moreover, HRQoL and anxiety will also be examined after 6 and 12 months.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ali Reza Safarpour, MD., Ph.D.; Phone Number: +98-7136281442; Email: safarpourar@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patients between 18-80 years' old
2. Patients who have received a diagnosis of UC at least 3 months prior to screening. The diagnosis of UC must be confirmed by endoscopic and histologic evidence.
3. Patients with the ability to give written informed consent and to be compliant with the schedule of intervention and assessments
4. Patients with mild (3-5) or moderate (6-11) UC, according to the Simple Clinical Colitis Activity Index

Exclusion Criteria:

1. Pregnant patients or those planning pregnancy
2. Patients receiving immunosuppressive agents for diseases other than UC
3. Patients with confirmed cancer, dysplasia, autoimmune, and rheumatology diseases
4. Patients who had surgery for UC treatment
5. Individuals with liver disease or abnormal liver enzymes and function tests (e.g. total bilirubin, aspartate aminotransferase (AST) or alanine aminotransferase (ALT)) at the screening visit
6. Patients who have any condition affecting oral drug absorption.
7. Subjects with known active or untreated GI infections including C.diff, CMV, HSV, HIV
8. Subjects with clinical features of CD; history of CD (Crohns colitis, or Ileo-colitis), clinical signs of fulminant colitis, toxic megacolon, or Microscopic Colitis, indeterminate Colitis, infectious Colitis, or ischemic colitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mild UC-Saffron 100; Mild UC patients, receiving 100 milligram (mg)/day saffron for 8 weeks (50 mg two times (BID)), n=10	Drug: Saffron 100; to Mild and Moderate UC patients
Experimental: Moderate UC-Saffron 100; Moderate UC patients, receiving100 mg/day saffron for 8 weeks (50 mg BID), n=10	Drug: Saffron 100; to Mild and Moderate UC patients
Experimental: Mild UC-Saffron 50; Mild UC patients, receiving 50 mg/day saffron for 8 weeks (25 mg BID), n=10	Drug: Saffron 50; to Mild and Moderate UC patients
Experimental: Moderate UC-Saffron 50; Moderate UC patients, receiving 50 mg/day saffron for 8 weeks (25 mg BID), n=10	Drug: Saffron 50; to Mild and Moderate UC patients
Placebo Comparator: Mild UC-placebo; Mild UC patients, receiving 2 tablets of placebo for 8 weeks, n=10	Drug: Placebo; to Mild and Moderate UC patients
Placebo Comparator: Moderate UC-placebo; Moderate UC patients, receiving 2 tablets of placebo for 8 weeks, n=10	Drug: Placebo; to Mild and Moderate UC patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in clinical response	Changes in clinical response will be assessed by "Simple Clinical Colitis Activity Index", which has a total score between 0 to 19. Higher scores are interpreted to higher disease activity (worse outcome).	4 and 8 weeks
Changes in the fecal calprotectin level		4 and 8 weeks
Changes in the serum levels of CRP		4 and 8 weeks
Changes in the serum levels of ESR		4 and 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the serum anti-inflammatory and pro-inflammatory markers	IL-1, IL-6, IL-10, IL-13RA2, IL18, IL17, TREM1, TNF- α, TNFR2, and oncostatin M (pg/ml)	8 week
Changes in the Health-related quality of life (HRQoL )	Changes in HRQoL will be assessed by a questionnaire, which has a total score between 9 to 63. Higher scores are interpreted to a higher quality of life (better outcome).	8, 24, and 48 weeks
Changes in the stool microbiome and transcriptome	Stool samples will be collected and after RNA extraction, reverse transcriptase qPCR will be performed. Small RNA sequencing libraries will also be constructed and16S rRNA gene analysis will be conducted.	8 week
Safety assessment (Incidence of Treatment-Emergent Adverse Events)	Any adverse events such as Gastrointestinal disorders, Psychiatric disorders, Nervous system disorders, and Immune system disorders will be assessed by the Common Terminology Criteria for Adverse Events Questionnaire.	8 week
Changes in the anxiety	Changes in anxiety will be assessed by Beck questionnaire, which has a total score between 0 to 63. Higher scores are interpreted to higher anxiety (worse outcome).	8, 24, and 48 weeks
Changes in the metabolomic profile of urine, stool, and saliva	Nuclear magnetic resonance will be used for assessment of the metabolomic profile of urine, stool, and saliva	8 weeks

Collaborators and Investigators

• Sponsor: Shiraz University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): February 1, 2025
• Study Completion (Anticipated): August 1, 2025

Study Registration Dates

• First Submitted: October 21, 2021
• First Submitted That Met QC Criteria: November 2, 2021
• First Posted (Actual): November 11, 2021

Study Record Updates

• Last Update Posted (Actual): May 11, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Ulcerative Colitis; saffron; inflammatory bowel disease; randomized double-blind clinical trial
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: 24540

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No