Safety Trial of Herbal Melanin in Gastritis Patients (RASATHEME)

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ClinicalTrials.gov Identifier: NCT03428568

Recruitment Status : Unknown

Verified December 2017 by King Abdullah International Medical Research Center.
Recruitment status was: Not yet recruiting

First Posted : February 9, 2018

Last Update Posted : February 9, 2018

Sponsor:

Information provided by (Responsible Party):

King Abdullah International Medical Research Center

Study Description

Brief Summary:

The aim of the study is to use Melanole, a herbal extract from Nigella sativa, for treatment of gastritis. The effect of Melanole will be compared between participants (including H. pylori and non-H.pylori infected patients), with the triple therapy and Standard of care treatment of gastritis, respectively.

All participants will be examined before and after the administration of Melanole. The results showing a relief of gastritis symptoms for non-H. pylori patients and partial or complete eradication of H. pylori for H.pylori infected patients will be evaluated.

Condition or disease	Intervention/treatment	Phase
Acid Dyspepsia Gastritis	Other: Herbal Melanin Drug: Nexium Drug: Amoxil Drug: Clarithromycin	Phase 2

Show detailed description

Detailed Description:

Background:

The melanin to be used in this study is a herbal melanin (HM) that has been extracted from the plant Nigella sativa. Nigella sativa was obtained from local market in Riyadh, Saudi Arabia. HM has been obtained from seed total powdered extract using standard extraction procedure and has been reported as a patent for the first time.The percentage of pure melanin in total Nigella sativa L. is 9% as identified using Electron Spin Resonance (ESR) and Fourier Transform- Infra Red (FI-IR) and calculated using wet chemical methods. Three different patches of Nigella sativa L that were obtained from different Nigella sativa L species were tested (Saudi, Ethiopian and Indian) and the same percentage of HM was obtained. The safety of HM has been tested and confirmed by different labs including lab for Quality and Safety and Industrial Research Institute(IRI) (see supplements 1 and 2). Similarly, the safety of the HM capsules have been tested at the Toxicology and Bioanalysis in King Faisal Specialist Hospital(KFSH) (see supplement 3). Moreover, the capsules have been approved and certified for free sale by the Ministry of Health at Lebanon.

Study Area:

The study will be performed in the gastroenterology clinic at National Guard Health Affairs(NGHA). Volunteers who participate in the study will be recruited from NGHA clinics. Participates are patients diagnosed with gastritis, both H. Pylori and non-H.Pylori infected, together with healthy volunteers.

The histological studies will be performed at the pathology department at NGHA.

Taking biopsies during endoscopy:

The best way to get tissue samples from the stomach is through a procedure called an esophagogastroduodenoscopy. It is more commonly known as an endoscopy or EGD. This is generally done as an outpatient procedure. The biopsies will be taken through the esophagogastroduodenoscopy (EGD) by a ultra-thin forceps, then will be saved in special container and send to the Laboratory for staining and microscopic examination. Under the microscope the pathologist will look for the abnormal mucosa , inflammation, ulceration , and helicobacter pylori gram negative micro-organism .During the procedure there is low chance of some complications which happened in 1: 10 000 , these include ; injury to the mucosa with bleeding and perforation , discomfort , sedation related complication like headache and nausea . These rare but the patient will be informed about it.

Study Subjects:

Patients with gastritis or showing gastritis symptoms will be enrolled in this study. Gastritis participate patients will be selected after detection of gastric lesions by undergoing routine diagnostic tests (such as endoscopy of upper digestive system).

Sample Size Calculation and Estimation:

The sample size has been estimated as 132 ( 22 subjects per group). The calculation and estimation have been done as follows:

Sample Size Calculation

The calculation of sample size was performed using Query Advisor V.7

Sample Size Estimated

The minimum number of Subjects needed in each group is 18, a two sided 95.0% confidence interval for the difference between a Group 1 proportion of 0.6 and Group 2 proportion of 0.2 based on the large sample normal approximation will extend 0.3 from the observed differences in proportions. The total required sample would be (6 groups x 18=108).The assumed withdrawal/dropout rate is 20% in each group (22 subjects per group), the final sample size would ne 132 subjects. The calculation of sample size was performed using Query Advisor V.7)

Data Collection method:

All data will be collected electronically and reported in Case Report Forms.

Data Cleaning:

Raw data will be processed in accordance with the best practices for raw data management to identify any inaccuracies or incompleteness in advance to the statistical analysis. In order to accomplish this task, all interval variables will be checked and summarized in terms of maximum and minimum values. Minimum and maximum values will be checked and compared against the nominal maximum and minimum value of each variable and variables with implausible values will be flagged. A similar process will be applied to categorical variables to identify any potential anomalies (miscode) by running a general frequency analysis.

Cohort Characterization:

All variables will be summarized and reported using descriptive statistics. Interval variables will be summarized and reported in terms of mean and standard deviation. Categorical variables will be summarized and reported in terms of frequency distribution. All variables will be compared across study groups using chi square and t test accordingly.

Primary Outcome(s) Analysis:

Chi square test will be used to compare the distribution of gastritis across the study groups. Results will be reported in terms of count, percent, and p-value. Significance will be declared at alfa less than 0.05. Binary logistic regression will be used to identify significant predictors of the primary outcomes. The statistical model will include key variables that showed significance with the primary outcome at the bivariate level. Results will be reported in terms of odds ratio, std. error, 95% confidence interval, and p-value. Significance will be declared at alfa less than 0.05.

Intent to treat analysis will be the approach in analyzing the data.

Statistical Analytical System(SAS) 9.2 will be used for all statistical analyses.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	132 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Open Label, Randomized, Single Site Clinical Trial To Compare The Safety Of Herbal Melanin Extracted From Nigella Sativa Seeds Vs Standard Of Care Treatment In Treating Gastritis Patients
Estimated Study Start Date :	March 2018
Estimated Primary Completion Date :	March 2019
Estimated Study Completion Date :	March 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Herbal Melanin Herbal melanin 1800 milligram(mg) orally thrice a day with meals (300mgx2 capsules)	Other: Herbal Melanin Herbal melanin extracted from Nigella sativa seeds Other Name: Melanole
Active Comparator: Nexium omeprazole 40 mg once per day for one month.	Drug: Nexium omeprazole Other Name: Aciloc
Experimental: H-Pylori infected : Herbal Melanin Herbal melanin 1800 mg orally thrice a day(TID) with meals (300 mg x2 capsules)	Other: Herbal Melanin Herbal melanin extracted from Nigella sativa seeds Other Name: Melanole
Active Comparator: nexium+ amoxil+clarithromycin omeprazole40 mg P.O. Twice per Day(BID) for one month + Amoxil 1000mg P.O. BID for 2 weeks+ Clarithromycin500 mg PO BID for two weeks. Omeprazole+Amoxil+clarithromycin is the standard triple therapy given	Drug: Nexium omeprazole Other Name: Aciloc Drug: Amoxil Antibiotic Drug: Clarithromycin Antibiotic Other Name: Klacid
Experimental: nexium +Herbal melanin omeprazole 40 mg P.O. BID for one month +1800 mg Herbal melanin PO TID (300mg x2 capsules) Omeprazole + Herbal melanin will be tested	Other: Herbal Melanin Herbal melanin extracted from Nigella sativa seeds Other Name: Melanole Drug: Nexium omeprazole Other Name: Aciloc
Experimental: Herbal melanin+amoxil+ clarithromycin Amoxil 1000mg P.O. BID for 2 weeks+ Clarithromycin500 mg PO BID for two weeks +1800 mg Herbal melanin PO TID(300 mg X 2 capsules) Herbal melanin+Amoxil+Clarithromycin will be tested	Other: Herbal Melanin Herbal melanin extracted from Nigella sativa seeds Other Name: Melanole Drug: Amoxil Antibiotic Drug: Clarithromycin Antibiotic Other Name: Klacid

Outcome Measures

Primary Outcome Measures :

Number of participants cured from acidity symptoms and H.Pylori -induced gastritis [ Time Frame: 6 months ]
Investigators hypothesize that HM is an effective candidate that can decrease stomach acidity and eradicate H.Pylori by working as Proton Pump Inhibitor(PPI) and/or antibacterial agent, respectively. Investigators suggest the role of HM in activation of Toll like Receptor 4 (TLR4)/Cycloxygenase2(COX2)/ProstaglandinE2( PGE2) as one underlying mechanism.

Secondary Outcome Measures :

Number of Participants cured with herbal melanin as compared to number of participants cured with standard of care for gastritis and H.Pylori-induced gastritis [ Time Frame: 6 months ]
Gastritis as indicated by improving the clinical presentation of gastritis and confirmed by end of treatment endoscopy and stool antigen test
Number of Participants between study groups having high expression of TLR4 and COX2 as assessed by Western blots procedure. [ Time Frame: 6 months ]
By using stomach biopsies for measuring the expression of TLR4 and COX 2 expression.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 60 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Males or Females between 18- 60 years
Willing to sign Informed Consent Form (ICF)
Women of Child bearing age will be asked to conduct a pregnancy test before enrolling in the study and offered contraceptives for the duration of the study participation
Clinical Pictures of Gastritis.
Histologically confirmed H- Pylori Gastritis or Non H- Pylori by one week from enrollment.

Exclusion Criteria:

Patients with disturbed gastrointestinal physiology (gastric surgery, vagotomy, Zollinger-Ellison syndrome)
Patients who have been treated with proton pump inhibitors during 3 weeks prior to inclusion
Patients who have been treated with antibiotics or bismuth containing drugs 1 month prior enrolling in the study
Patient with pyloric stenosis
Patient with Hematologic disorder
Patient with congestive heart disease
Women who are pregnant or lactating
Current or past history of malignancy
Drug abuser and chronic alcoholism
Patients currently participating in any other clinical trial of any kind

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03428568

Contacts

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Contact: Adila SA Elobeid, PhD	+966553543096	adilasalihelobeid@gmail.com
Contact: khizra sultana, Masters	+966542403883	khizzy31@gmail.com

Sponsors and Collaborators

King Abdullah International Medical Research Center

Investigators

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Principal Investigator:	Adila SA Elobeid, PhD	Ministry of National Guard

More Information

Publications:

El-Obeid A, Al-Harbi S, Al-Jomah N, Hassib A. Herbal melanin modulates tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) production. Phytomedicine. 2006 May;13(5):324-33. Epub 2005 Sep 19.

Biotechnological Method for Production of Melanin Pigments. Patent, award by Swedish PRV Patent office-Stockholm 2011 and United Nations PCT-WIPO 2011. Registered in US &Canada

Extraction of melanin from Nigella sativa L. Patent No. 451, Khartoum, Sudan. 1998.

Tortora, G.J. and Grabowski, S.R. (2003). Principles of Anatomy and Physiology. 10th ed. John Wiley& Sons, Inc, NJ, p.889.).

Parkin DM. International variation. Oncogene. 2004 Aug 23;23(38):6329-40. Review.

Peleteiro B, Bastos A, Ferro A, Lunet N. Erratum to: Prevalence of Helicobacter pylori Infection Worldwide: A Systematic Review of Studies with National Coverage. Dig Dis Sci. 2015 Sep;60(9):2849. doi: 10.1007/s10620-015-3779-5.

Ayala G, Escobedo-Hinojosa WI, de la Cruz-Herrera CF, Romero I. Exploring alternative treatments for Helicobacter pylori infection. World J Gastroenterol. 2014 Feb 14;20(6):1450-69. doi: 10.3748/wjg.v20.i6.1450. Review.

Hawkins C, Hanks GW. The gastroduodenal toxicity of nonsteroidal anti-inflammatory drugs: a review of the literature. J Pain Symptom Manage. 2000 Aug;20(2):140-51. Review.

El-Tahir, K. E. H.; Hassib, A. M.; El-Hag, H.; Ponten, F.; Westermark, B. El- Obeid Adila (2009). Anti-ulcerogenic effects of Nigella sativa Melanin. Sudan Patent No. 1683.

Mimura T, Maeda K, Tsujibo H, Satake M, Fujita T. Studies on biological activities of melanin from marine animals. II. Purification of melanin from Octopus vulgaris Cuvier and its inhibitory activity on gastric juice secretion in rats. Chem Pharm Bull (Tokyo). 1982 Apr;30(4):1508-12.

Mimura T, Maeda K, Terada T, Oda Y, Morishita K, Aonuma S. Studies on biological activities of melanin from marine animals. III. Inhibitory effect of SM II (low molecular weight melanoprotein from squid) on phenylbutazone-induced ulceration in gastric mucosa in rats, and its mechanism of action. Chem Pharm Bull (Tokyo). 1985 May;33(5):2052-60.

El-Dakhakhny M, Barakat M, El-Halim MA, Aly SM. Effects of Nigella sativa oil on gastric secretion and ethanol induced ulcer in rats. J Ethnopharmacol. 2000 Sep;72(1-2):299-304.

Kanter M, Demir H, Karakaya C, Ozbek H. Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats. World J Gastroenterol. 2005 Nov 14;11(42):6662-6.

Seniuk OF, Gorovoj LF, Beketova GV, Savichuk HO, Rytik PG, Kucherov II, Prilutskay AB, Prilutsky AI. Anti-infective properties of the melanin-glucan complex obtained from medicinal tinder bracket mushroom, Fomes fomentarius (L.: Fr.) Fr. (Aphyllophoromycetideae). Int J Med Mushrooms. 2011;13(1):7-18.

Peterson WL. The role of antisecretory drugs in the treatment of Helicobacter pylori infection. Aliment Pharmacol Ther. 1997 Apr;11 Suppl 1:21-5. Review.

Salem EM, Yar T, Bamosa AO, Al-Quorain A, Yasawy MI, Alsulaiman RM, Randhawa MA. Comparative study of Nigella Sativa and triple therapy in eradication of Helicobacter Pylori in patients with non-ulcer dyspepsia. Saudi J Gastroenterol. 2010 Jul-Sep;16(3):207-14. doi: 10.4103/1319-3767.65201.

Poelmans J, Feenstra L, Demedts I, Rutgeerts P, Tack J. The yield of upper gastrointestinal endoscopy in patients with suspected reflux-related chronic ear, nose, and throat symptoms. Am J Gastroenterol. 2004 Aug;99(8):1419-26.

Poelmans J, Tack J, Feenstra L. Chronic middle ear disease and gastroesophageal reflux disease: a causal relation? Otol Neurotol. 2001 Jul;22(4):447-50.

Poelmans J, Feenstra L, Tack J. Determinants of long-term outcome of patients with reflux-related ear, nose, and throat symptoms. Dig Dis Sci. 2006 Feb;51(2):282-8.

Schmausser B, Andrulis M, Endrich S, Müller-Hermelink HK, Eck M. Toll-like receptors TLR4, TLR5 and TLR9 on gastric carcinoma cells: an implication for interaction with Helicobacter pylori. Int J Med Microbiol. 2005 Jun;295(3):179-85.

Schmausser B, Andrulis M, Endrich S, Lee SK, Josenhans C, Müller-Hermelink HK, Eck M. Expression and subcellular distribution of toll-like receptors TLR4, TLR5 and TLR9 on the gastric epithelium in Helicobacter pylori infection. Clin Exp Immunol. 2004 Jun;136(3):521-6.

El-Obeid A, Hassib A, Pontén F, Westermark B. Effect of herbal melanin on IL-8: a possible role of Toll-like receptor 4 (TLR4). Biochem Biophys Res Commun. 2006 Jun 16;344(4):1200-6. Epub 2006 May 2.

Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004 Jul 23;118(2):229-41.

Fukata M, Chen A, Klepper A, Krishnareddy S, Vamadevan AS, Thomas LS, Xu R, Inoue H, Arditi M, Dannenberg AJ, Abreu MT. Cox-2 is regulated by Toll-like receptor-4 (TLR4) signaling: Role in proliferation and apoptosis in the intestine. Gastroenterology. 2006 Sep;131(3):862-77.

Zheng L, Riehl TE, Stenson WF. Regulation of colonic epithelial repair in mice by Toll-like receptors and hyaluronic acid. Gastroenterology. 2009 Dec;137(6):2041-51. doi: 10.1053/j.gastro.2009.08.055. Epub 2009 Sep 2.

Hoogerwerf et al. 2006. Hoogerwerf, W.J., Pasricha, P.J., 2006. Pharmacotherapy of gastric acidity,peptic ulcer and gastroesophageal reflux disease: Goodman and Gilman's.The pharmacological basis of therapeutics. McGraw-Hill, United States, pp.869-882).

Wada A, Ogushi K, Kimura T, Hojo H, Mori N, Suzuki S, Kumatori A, Se M, Nakahara Y, Nakamura M, Moss J, Hirayama T. Helicobacter pylori-mediated transcriptional regulation of the human beta-defensin 2 gene requires NF-kappaB. Cell Microbiol. 2001 Feb;3(2):115-23.

Biragyn A, Ruffini PA, Leifer CA, Klyushnenkova E, Shakhov A, Chertov O, Shirakawa AK, Farber JM, Segal DM, Oppenheim JJ, Kwak LW. Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science. 2002 Nov 1;298(5595):1025-9.

Ohara T, Morishita T, Suzuki H, Masaoka T, Nagata H, Hibi T. Pathophysiological role of human beta-defensins 2 in gastric mucosa. Int J Mol Med. 2004 Dec;14(6):1023-7.

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Responsible Party:	King Abdullah International Medical Research Center
ClinicalTrials.gov Identifier:	NCT03428568
Other Study ID Numbers:	RC15/152/R
First Posted:	February 9, 2018 Key Record Dates
Last Update Posted:	February 9, 2018
Last Verified:	December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by King Abdullah International Medical Research Center:


Herbal Melanin H.Pylori

Additional relevant MeSH terms:

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Gastritis Dyspepsia Signs and Symptoms, Digestive Gastroenteritis Gastrointestinal Diseases Digestive System Diseases Stomach Diseases Clarithromycin	Anti-Bacterial Agents Anti-Infective Agents Protein Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors

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