Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06213857 |
| Other study ID # |
Silymarin in UC |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 2024 |
| Est. completion date |
March 2025 |
Study information
| Verified date |
January 2024 |
| Source |
Tanta University |
| Contact |
Ahmad A Ahmad Eltayeb, Cl.Ph |
| Phone |
+201140399467 |
| Email |
PG_165473[@]pharm.tanta.edu.eg |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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 (4g\day induction & 2g\day
maintenance) only for 6 months.
- Group Ⅱ (silymarin group): 22 patients will receive mesalamine (4g\day induction &
2g\day maintenance) and silymarin (140 mg\day) 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.
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, Crohn's 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 patient's 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 (e.g., 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].
