Ignite Creation Date:
2024-05-06 @ 8:00 PM
Last Modification Date:
2024-10-26 @ 3:18 PM
Study NCT ID:
NCT06213857
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-01-19
First Post:
2024-01-09
Brief Title:
Beneficial Effect of Silymarin in Ulcerative Colitis
Sponsor:
Tanta University
Organization:
Tanta University
Study Overview
Official Title:
Clinical Study Evaluating the Possible Beneficial Effect of Silymarin in Patients With Ulcerative Colitis
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this clinical trial is to evaluate the possible beneficial effect of silymarin in Ulcerative Colitis adult patients receiving mesalamine This is trial that will be conducted on 44 adult patients with newly diagnosed Ulcerative Colitis Patients will be enrolled after obtaining an informed consent from them or their guardians
Patients will be recruited from Rajhy Hospital Outpatient Clinics and Health Insurance Outpatient Clinics at Mabarra Hospital in Assiut Egypt The patients will be randomized based on hospital admission days into two groups
Group Ⅰ control group 22 patients will receive mesalamine 4gday induction 2gday maintenance only for 6 months
Group Ⅱ silymarin group 22 patients will receive mesalamine 4gday induction 2gday maintenance and silymarin 140 mgday for 6 months
The primary outcome will be clinical improvement defined as a 2 point or more decrease in the Mayo score from baseline The secondary outcomes will be the change in the level of fecal calprotectin superoxide dismutase and TNF-α
Patients will be recruited from Rajhy Hospital Outpatient Clinics and Health Insurance Outpatient Clinics at Mabarra Hospital in Assiut Egypt The patients will be randomized based on hospital admission days into two groups
Group Ⅰ control group 22 patients will receive mesalamine 4gday induction 2gday maintenance only for 6 months
Group Ⅱ silymarin group 22 patients will receive mesalamine 4gday induction 2gday maintenance and silymarin 140 mgday for 6 months
The primary outcome will be clinical improvement defined as a 2 point or more decrease in the Mayo score from baseline The secondary outcomes will be the change in the level of fecal calprotectin superoxide dismutase and TNF-α
Detailed Description:
Inflammatory Bowel Disease IBD is a debilitating progressive chronic inflammatory disorder of the small intestine and colon characterized by alternative phases of clinical relapse and remission IBD includes two types Crohns Disease CD and Ulcerative Colitis UC CD can affect any part of the gastrointestinal tract whereas UC involves only rectum and colon 1
UC is a chronic idiopathic inflammatory disease characterized by relapsing and remitting mucosal inflammation involving the colon and the rectum The peak age of disease onset is between ages 30 years and 40 years 2 Although the exact etiology of UC remains uncertain a combination of patients immune response genetics microbiome and environment plays an important role in the development of the inflammation 3 The incidence of UC is similarly in men and women but varies with ethnicity 4 UC has the highest incidence in the USA UK and Sweden In Egypt the prevalence is low but the newly diagnosed cases are increasing rapidly 5
The most common signs and symptoms of UC include bloody stool diarrhea vomiting fatigue abdominal pain fever weight loss with enhanced risk of colorectal cancer and several extra intestinal manifestations eg arthritis uveitis and skin disease 6 Symptoms are often non-specific and patients frequently suffer from long-lasting subclinical disease activity that is difficult to monitor and treat 7
A chronic uncontrolled immune response is the net result of excessive immune activity of effector lymphocytes with increased production of pro-inflammatory cytokines while regulatory immune cells and mediators fail to maintain tissue homeostasis 8 Chronically active inflammation is directly coupled to the generation and release by immune cells of reactive oxygen species ROS serving as important signaling molecules that contribute to their immunological functions 9 The continuous release of ROS in the local microenvironment of actively inflamed mucosal lesions causes extensive cellular and molecular damage leading to intestinal inflammation and increased tissue destruction 10
Oxidative stress which is an imbalance between ROS and antioxidant activity as the result of either ROS overproduction or a decreased antioxidant activity has been proposed as one of the major mechanism involved in the pathophysiology of UC 11 Once the free radicals are formed this reactive species begins to interact with the molecular complexes causing cellular oxidative damage Under physiological conditions their generation is controlled by the antioxidant system which consists of enzymes such as superoxide dismutase SOD catalase and glutathione peroxidase GPX 12
Increased ROS have destructive effects which can affect lipids proteins and nucleic acids that causes lipid peroxidation enzymatic dysfunction and DNA strand break products 13 These destructive effects can be removed by antioxidant balance which acts like free radical scavengers or cellular oxidation inhibitors The main cellular antioxidant enzymes involved in the inhibition are catalase SOD and GPX 14 Activated neutrophils and macrophages are responsible for ROS generation and their levels can be correlated with the severity of inflammation 15 It has been shown that IL 1 and TNFα cytokines can be inhibited by antioxidants administered to UC patients 16
The American College of Gastroenterology ACG recommends performing a complete blood count CBC and measuring inflammatory markers such as c-reactive protein CRP erythrocyte sedimentation rate ESR It also recommends measuring Liver transaminases aspartate and alanine aminotransferase 17 Measurement of fecal calprotectin is useful for screening intestinal inflammation associated with disease activity 18
Silymarin milk thistle an extract obtained from Silybum marianum seeds is one of these natural sources containing a complex of flavonolignans with a potent intracellular antioxidant property The first usage of Milk thistle was for its hepatoprotective and antioxidant activities but in the recent years its benefit has been reported in control of immune based murine colitis by healing of bowel histology and reduction of bowel inflammatory cytokines especially TNF-α interleukin-1β IL-1β and nuclear factor κB NF-κB 19 Silymarin has numerous health benefits and exerts its effects via various molecular mechanisms Silymarin has anti-viral immunomodulation anti-inflammatory effects as well as antioxidant properties by scavenging free radicals and increasing the glutathione concentrations anti-arthritis antidiabetic protective and wound healing effects 20
UC is a chronic idiopathic inflammatory disease characterized by relapsing and remitting mucosal inflammation involving the colon and the rectum The peak age of disease onset is between ages 30 years and 40 years 2 Although the exact etiology of UC remains uncertain a combination of patients immune response genetics microbiome and environment plays an important role in the development of the inflammation 3 The incidence of UC is similarly in men and women but varies with ethnicity 4 UC has the highest incidence in the USA UK and Sweden In Egypt the prevalence is low but the newly diagnosed cases are increasing rapidly 5
The most common signs and symptoms of UC include bloody stool diarrhea vomiting fatigue abdominal pain fever weight loss with enhanced risk of colorectal cancer and several extra intestinal manifestations eg arthritis uveitis and skin disease 6 Symptoms are often non-specific and patients frequently suffer from long-lasting subclinical disease activity that is difficult to monitor and treat 7
A chronic uncontrolled immune response is the net result of excessive immune activity of effector lymphocytes with increased production of pro-inflammatory cytokines while regulatory immune cells and mediators fail to maintain tissue homeostasis 8 Chronically active inflammation is directly coupled to the generation and release by immune cells of reactive oxygen species ROS serving as important signaling molecules that contribute to their immunological functions 9 The continuous release of ROS in the local microenvironment of actively inflamed mucosal lesions causes extensive cellular and molecular damage leading to intestinal inflammation and increased tissue destruction 10
Oxidative stress which is an imbalance between ROS and antioxidant activity as the result of either ROS overproduction or a decreased antioxidant activity has been proposed as one of the major mechanism involved in the pathophysiology of UC 11 Once the free radicals are formed this reactive species begins to interact with the molecular complexes causing cellular oxidative damage Under physiological conditions their generation is controlled by the antioxidant system which consists of enzymes such as superoxide dismutase SOD catalase and glutathione peroxidase GPX 12
Increased ROS have destructive effects which can affect lipids proteins and nucleic acids that causes lipid peroxidation enzymatic dysfunction and DNA strand break products 13 These destructive effects can be removed by antioxidant balance which acts like free radical scavengers or cellular oxidation inhibitors The main cellular antioxidant enzymes involved in the inhibition are catalase SOD and GPX 14 Activated neutrophils and macrophages are responsible for ROS generation and their levels can be correlated with the severity of inflammation 15 It has been shown that IL 1 and TNFα cytokines can be inhibited by antioxidants administered to UC patients 16
The American College of Gastroenterology ACG recommends performing a complete blood count CBC and measuring inflammatory markers such as c-reactive protein CRP erythrocyte sedimentation rate ESR It also recommends measuring Liver transaminases aspartate and alanine aminotransferase 17 Measurement of fecal calprotectin is useful for screening intestinal inflammation associated with disease activity 18
Silymarin milk thistle an extract obtained from Silybum marianum seeds is one of these natural sources containing a complex of flavonolignans with a potent intracellular antioxidant property The first usage of Milk thistle was for its hepatoprotective and antioxidant activities but in the recent years its benefit has been reported in control of immune based murine colitis by healing of bowel histology and reduction of bowel inflammatory cytokines especially TNF-α interleukin-1β IL-1β and nuclear factor κB NF-κB 19 Silymarin has numerous health benefits and exerts its effects via various molecular mechanisms Silymarin has anti-viral immunomodulation anti-inflammatory effects as well as antioxidant properties by scavenging free radicals and increasing the glutathione concentrations anti-arthritis antidiabetic protective and wound healing effects 20
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None