Clinical trial NCT05957432: Efficacy and Safety of Black Seed Oil With Vonoprazan Based Triple Therapy in Treatment of Helicobacter Pylori
Official title: Efficacy and Safety of Black Seed Oil With Vonoprazan Based Triple Therapy in Treatment of Helicobacter Pylori
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Helicobacter Pylori Infection
Keywords: Helicobacter pylori infection
vonoprazan
black seed oil
oxidative stress
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2023-07-24
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to:

• Evaluation of efficacy and safety of adding black seed oil with vonoprazan triple therapy ( vonoprazan ,clarithromycin and amoxicillin ) in eradication of Helicobacter pylori infection and this will be done through evaluation of:

A. Efficacy by:

1. determination of successful eradication,which will be considered to be achieved on the basis of a negative stool antigen test four weeks after the end of treatment using Stool Ag test
2. The effect of N. Sativa on:

I. Oxidative stress by measuring MDA II. Inflammation by measuring IL1B as inflammatory markers

B. Safety will be done through:

Monitoring of expected treatment related adverse effects (black seed oil and vonoprazan triple therapy ) will be done through the whole study period.

C. Symptoms evaluation using the Gastrointestinal symptom rating scale D. Assessment of patient's quality of life using SF36 questionnaire

Detailed description: Helicobacter pylori infection is a highly prevalent chronic bacterial infection in humans worldwide affecting approximately 50% of the global population. H. pylori infection is highly prevalent in the Middle East and North Africa (MENA) region .

It may cause chronic gastritis, peptic ulcer disease, atrophic gastritis, and intestinal metaplasia that predispose to gastric cancer . Moreover, H. pylori may contribute to insulin resistance and metabolic syndrome as well as autoimmune and hematologic diseases . H. pylori was classified as a class I human carcinogen .

About 25 years ago, a proton pump inhibitor (PPI)-based regimen was introduced as a first-line treatment of H. pylori infection. PPI-based therapy showed a superior efficacy to non-PPI-based therapy in terms of H. pylori eradication.The PPI-based triple therapy, which consists of PPI, amoxicillin, and clarithromycin, has been a worldwide choice for H. pylori eradication. However, the treatment regimen is still a concern in light of the decreasing eradication rates owing to the increased antibiotic resistance of H. pylori.

Recently, vonoprazan, a novel potassium-competitive acid blocker, has been used in H. pylori eradication therapy in order to increase the eradication rate .

Vonoprazan (VPZ) works by competing for potassium on the luminal side of the parietal cell and causes rapid and reversible inhibition of H-K ATPase and therefore inhibits extended acid secretion. In contrast to PPIs, Vonoprazan is a more potent inhibitor of acid secretion. It has a rapid onset of action, less anti-secretory variability, greater safety, and better tolerability .

A meta-analysis of 10 studies by Jung et al. included research comparing the efficacy of a vonaprazan-based triple therapy group (vonoprazan 20 mg bid., amoxicillin 750 mg bid., and clarithromycin 200 or 400 mg bid. for 7 days) with that of a PPI-based triple therapy group (omeprazole 20 mg or lansoprazole 30 mg bid., amoxicillin 750 mg bid., and clarithromycin 200 or 400 mg bid. for 7 days). The eradication rates of vonoprazan-based triple therapy and PPI-based triple therapy were 87.9% and 72.8% (pooled risk ratio \[RR\] 1.02, 95% confidence interval \[CI\] 1.15-1.24), respectively.

The increasing rate of anti-H.Pylori drug resistance, medication costs, side effects, and the patient's incompliance make the treatment of H. pylori infection a global challenge. Therefore, there is a need to look for new safe, feasible, and affordable alternatives that are effective against H. pylori.

In recent years, the use of medicinal plants has been considered due to their potential effects on human health and the better management of diseases. Meanwhile, Nigella sativa is one of the most useful medicinal plants, which has been traditionally used for the treatment of many acute and chronic diseases and the promotion of human health.

The seeds of N. sativa, commonly known as black seed or black cumin, have rich biological active compounds such as thymoquinone (TQ), dithymoquinone, nigellicine, nigellidine, thymol, and carvacrol. All these compounds are synergistically responsible for beneficial pharmacological properties ; including antioxidant, anti-inflammatory, anticancer, antimicrobial, antiparasite, immunopotentiating action, gastroprotective, hepatoprotective, hypoglycemic, analgesic effects, and so forth.

In various studies, the antibacterial effects of this plant and its ingredients have been proven. The essential oil of N. sativa and its components like TQ and hydrothymoquinone were reported to be lethal to some Gram-negative and Gram-positive bacteria.

In an in vitro experiment, N. sativa extract inhibited the growth of all H. pylori strains within 60 min. The essential oil obtained from N. sativa was found to be safer than the volatile oil against different cell lines. Human case reports indicated allergic contact dermatitis following the use of some preparations containing N. sativa. However, clinical trials did not report any severe adverse effects following consumption N. sativa.

In a clinical trial, it was shown that N. sativa seed powder possessed anti-H. pylori activity comparable to triple therapy and improved dyspepsia symptoms in infected patients. It seems that the combination of N. sativa with antibiotics can reduce the resistance of H. pylori colonies and improve antibiotic efficacy.

H. pylori infection induces an inflammatory response that is also oxidative. The gastric epithelium and the bacteria induce production of interleukin-8 (IL-8) and malondialdehyde (MDA) that contributes to the generation of great amounts of toxic reactive oxygen species (ROS), with marked infiltration of inflammatory cells, and can elicit induction of interleukin-1β (IL-1β), interleukin-6 (IL-6), IL-8, interleukin-12 (IL-12), tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) .

IL-1β has biological effects that qualify it as arguably the most important cytokine in the gastrointestinal tract. Its proinflammatory properties contribute to the defence against pathogens, its antisecretory and cytoprotective effects contribute to the healing process following challenge to the integrity of the mucosa, and its acid inhibitory effects may have a profound effect on the natural history of H pylori infection.

Several studies have shown that NS has been proven to have antioxidant capabilities by reducing the production of reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA).

Previous researches showed that supplementation of NS would significantly decrease the production of MDA and SOD in patients compared to controls.Interestingly, N. sativa Interestingly, TQ was found to exert its anti-inflammatory properties through the prevention of the expression of IL-6, IL-1β, and cyclooxygenase-2 in experimental rats.

No clinical trial has yet evaluated the effects of N. sativa oil concurrent with vonoprazan based regimens on the eradication of H. pylori infection. Therefore, The investigators performed this trial to evaluate the anti-H. Pylori properties of N. sativa concurrent with vonoprazan triple therapy on the eradication of bacteria, dyspepsia symptoms and quality of life in patients with this infection. Furthermore, the investigators measured the effects of N. sativa on oxidative stress and inflammatory markers in infected patients.

Eligibility criteria: Inclusion Criteria:

* Male or female patients
* Age 18 to 75 years old
* Patients with confirmed H. pylori infection by stool Ag test who had not received prior eradication therapy

Exclusion Criteria:

* History of hypersensitivity / allergy to any of the study drugs i.e., Esomeprazole, vonoprazan, penicillin, or clarithromycin
* History of previous H. pylori eradication therapy
* History of using PPIs, antibiotics that affect H. pylori within 4 weeks
* History of gastric malignancy or surgery
* Serious cardiovascular, pulmonary, renal, hepatic disorders or active malignancy
* Pregnancy or breast feeding
* History of drug abuse or active alcohol abuse

Primary outcomes:
measure: Stool antigen test at baseline ( pre-intervention)
timeFrame: at baseline for diagnosis of helicobacter pylori (before start of triple therapy )
measure: Change of Stool antigen test after 4 weeks from triple therapy
timeFrame: after 4 weeks from triple therapy
Secondary outcomes:
measure: Change in MDA (oxidative stress marker) levels
timeFrame: change from baseline at 6 weeks
measure: Change in Interleukin 1B ( inflammatory markers ) levels
timeFrame: change from baseline at 6 weeks
measure: "Gastrointestinal symptom rating scale"
timeFrame: change from baseline at 6 weeks
measure: SF36 questionnaire
timeFrame: change from baseline at 6 weeks
measure: Safety and tolerability
timeFrame: every week for 4 weeks
Other outcomes:
Locations:
city: Zagazig
country: Egypt
facility: GIT department zagazig university hospital
Study officials:
affiliation: faculty of pharmacy Ain shams university
name: sara M zaky, ass.prof
role: PRINCIPAL_INVESTIGATOR
affiliation: faculty of medicine zagazig university
name: yasser A Elnaggar, prof
role: STUDY_CHAIR
affiliation: faculty of pharmacy Ainshams university
name: sara F Mohamed, lecturer
role: STUDY_CHAIR
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