Saffron and Ulcerative Colitis

Study Overview
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Brief Summary
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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.

Detailed Description
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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: Mild UC patients, receiving100 milligram (mg)/day saffron for 8 weeks (50 mg two times (BID)), n=10 Moderate UC patients, receiving100 mg/day saffron for 8 weeks (50 mg BID), n=10 Mild UC patients, receiving 50 mg/day saffron for 8 weeks (25 mg BID), n=10 Moderate UC patients, receiving 50 mg/day saffron for 8 weeks (25 mg BID), n=10 Mild UC patients, receiving 2 tablets of placebo for 8 weeks, n=10 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.

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

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Saffron 100
* Drug: Saffron 50
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients between 18-80 years' old 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. Patients with the ability to give written informed consent and to be compliant with the schedule of intervention and assessments Patients with mild (3-5) or moderate (6-11) UC, according to the Simple Clinical Colitis Activity Index Exclusion Criteria: Pregnant patients or those planning pregnancy Patients receiving immunosuppressive agents for diseases other than UC Patients with confirmed cancer, dysplasia, autoimmune, and rheumatology diseases Patients who had surgery for UC treatment 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 Patients who have any condition affecting oral drug absorption. Subjects with known active or untreated GI infections including C.diff, CMV, HSV, HIV 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Sixty eligible patients will be recruited and randomized into 6 groups to receive either saffron capsule or placebo.
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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saffron, Ulcerative Colitis, inflammatory bowel disease, randomized double-blind clinical trial