Melatonin for Prevention of Radiation Induced Oral Mucositis

Oral Mucositis (Ulcerative) Due to Radiation Clinical Trial

Official title:

The Effectiveness of Melatonin in Prevention of Radiation-induced Oral Mucositis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03833570
• Other study ID #: 0008839
• Status: Completed
• Phase: Phase 2
• Start date: January 12, 2018
• Est. completion date: December 1, 2018

Study information

• Verified date: June 2019
• Source: Alexandria University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main aim of this study was to evaluate the effectiveness of melatonin in prevention of radiation induced oral mucositis clinically and biochemically.

Description:

The study was designed as randomized, controlled, clinical trial. patients who were undergoing chemoradiation were divided into two groups: Group I: was given conventional treatment. Group II: was given melatonin therapy in combination with the conventional treatment.

All patients were clinically evaluated at the start the radiotherapy, three weeks and six weeks later for pain and oral mucositis severity. in addition, the total antioxidant capacity of the melatonin was evaluated at the start of the radiotherapy and six weeks later.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 1, 2018
• Est. primary completion date: November 9, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years and older

Eligibility

Inclusion Criteria:

• Patients who are going to receive radiotherapy as a treatment of head and neck cancer either as postoperative (adjuvant) therapy or definitive therapy.

• Patients whose radiotherapy treatment planned dose is between 60-70 Gy.

• Patients who had received chemotherapy prior to radiotherapy or are going to receive chemotherapy in concomitant to radiotherapy.

Exclusion Criteria:

• Patients under Anticoagulants such as warfarin, heparin, or aspirin.

• Patients under Fluvoxamine (Luvox) and Nifedipine medications.

• Patients whose radiotherapy treatment planned dose is lower than 60 Gy.

• Pregnant and lactating women.

• Patients suffering from any uncontrolled systemic diseases (such as diabetes, cardiovascular, liver disorder, renal dysfunction)

• Patients with findings of any physical or mental abnormality which would interfere with or be affected by the study procedure.

Related Conditions & MeSH terms

• Mucositis
• Oral Mucositis (Ulcerative) Due to Radiation
• Stomatitis

Intervention

Dietary Supplement:
• Rapid Release Capsules Melatonin, 10 mg
Melatonin is a dietary supplement which is naturally produced in the body and closely involved in the natural sleep cycle. recently topical and systemic melatonin supplements. have been proposed as a new therapeutic modality for oral mucositis due to its anti-cancer, anti-inflammatory, and anti-oxidant effects.

Drug:
• Miconaz oral gel
Antifungal agent
• BBC oral spray
Topical anesthetics and anti-inflammatory agent
• Oracure gel
Topical analgesic gel

Other:
• Alkamisr sachets
Sodium bicarbonate mouthwash

Locations

Country	Name	City	State
Egypt	Outpatient clinic of Department of Clinical Oncology, Faculty of Medicine, Alexandria University	Alexandria

Sponsors (2)

Lead Sponsor	Collaborator
Hams Hamed Abdelrahman	Alexandria University

Country where clinical trial is conducted

Egypt, 

References & Publications (23)

Brasure M, MacDonald R, Fuchs E, Olson CM, Carlyle M, Diem S, Koffel E, Khawaja IS, Ouellette J, Butler M, Kane RL, Wilt TJ. Management of Insomnia Disorder [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2015 Dec. Available from http://www.ncbi.nlm.nih.gov/books/NBK343503/ — View Citation

Campos MI, Campos CN, Aarestrup FM, Aarestrup BJ. Oral mucositis in cancer treatment: Natural history, prevention and treatment. Mol Clin Oncol. 2014 May;2(3):337-340. Epub 2014 Feb 7. Review. — View Citation

Duncan GG, Epstein JB, Tu D, El Sayed S, Bezjak A, Ottaway J, Pater J; National Cancer Institute of Canada Clinical Trials Group. Quality of life, mucositis, and xerostomia from radiotherapy for head and neck cancers: a report from the NCIC CTG HN2 randomized trial of an antimicrobial lozenge to prevent mucositis. Head Neck. 2005 May;27(5):421-8. — View Citation

Feller L, Essop R, Wood NH, Khammissa RA, Chikte UM, Meyerov R, Lemmer J. Chemotherapy- and radiotherapy-induced oral mucositis: pathobiology, epidemiology and management. SADJ. 2010 Sep;65(8):372-4. — View Citation

Hardeland R, Pandi-Perumal SR, Cardinali DP. Melatonin. Int J Biochem Cell Biol. 2006 Mar;38(3):313-6. Epub 2005 Sep 27. Review. — View Citation

Harris DJ. Cancer treatment-induced mucositis pain: strategies for assessment and management. Ther Clin Risk Manag. 2006 Sep;2(3):251-8. — View Citation

Koracevic D, Koracevic G, Djordjevic V, Andrejevic S, Cosic V. Method for the measurement of antioxidant activity in human fluids. J Clin Pathol. 2001 May;54(5):356-61. — View Citation

Lee CS, Ryan EJ, Doherty GA. Gastro-intestinal toxicity of chemotherapeutics in colorectal cancer: the role of inflammation. World J Gastroenterol. 2014 Apr 14;20(14):3751-61. doi: 10.3748/wjg.v20.i14.3751. Review. — View Citation

Lemoine P, Zisapel N. Prolonged-release formulation of melatonin (Circadin) for the treatment of insomnia. Expert Opin Pharmacother. 2012 Apr;13(6):895-905. doi: 10.1517/14656566.2012.667076. Epub 2012 Mar 19. Review. — View Citation

Lyseng-Williamson KA. Melatonin prolonged release: in the treatment of insomnia in patients aged =55 years. Drugs Aging. 2012 Nov;29(11):911-23. doi: 10.1007/s40266-012-0018-z. Review. — View Citation

Maria OM, Eliopoulos N, Muanza T. Radiation-Induced Oral Mucositis. Front Oncol. 2017 May 22;7:89. doi: 10.3389/fonc.2017.00089. eCollection 2017. Review. — View Citation

McCormack HM, Horne DJ, Sheather S. Clinical applications of visual analogue scales: a critical review. Psychol Med. 1988 Nov;18(4):1007-19. Review. — View Citation

Mihandoost E, Shirazi A, Mahdavi SR, Aliasgharzadeh A. Can melatonin help us in radiation oncology treatments? Biomed Res Int. 2014;2014:578137. doi: 10.1155/2014/578137. Epub 2014 May 11. Review. — View Citation

Moslehi A, Taghizadeh-Ghehi M, Gholami K, Hadjibabaie M, Jahangard-Rafsanjani Z, Sarayani A, Javadi M, Esfandbod M, Ghavamzadeh A. N-acetyl cysteine for prevention of oral mucositis in hematopoietic SCT: a double-blind, randomized, placebo-controlled trial. Bone Marrow Transplant. 2014 Jun;49(6):818-23. doi: 10.1038/bmt.2014.34. Epub 2014 Mar 10. — View Citation

Najeeb S, Khurshid Z, Zohaib S, Zafar MS. Therapeutic potential of melatonin in oral medicine and periodontology. Kaohsiung J Med Sci. 2016 Aug;32(8):391-6. doi: 10.1016/j.kjms.2016.06.005. Epub 2016 Jul 25. Review. — View Citation

Rai B, Kaur J, Jacobs R, Singh J. Possible action mechanism for curcumin in pre-cancerous lesions based on serum and salivary markers of oxidative stress. J Oral Sci. 2010 Jun;52(2):251-6. — View Citation

Shirzad A, Pouramir M, Seyedmajidi M, Jenabian N, Bijani A, Motallebnejad M. Salivary total antioxidant capacity and lipid peroxidation in patients with erosive oral lichen planus. J Dent Res Dent Clin Dent Prospects. 2014 Winter;8(1):35-9. doi: 10.5681/joddd.2014.006. Epub 2014 Mar 5. — View Citation

Sonis ST. Oral mucositis in cancer therapy. J Support Oncol. 2004 Nov-Dec;2(6 Suppl 3):3-8. Review. — View Citation

Villa A, Sonis ST. Mucositis: pathobiology and management. Curr Opin Oncol. 2015 May;27(3):159-64. doi: 10.1097/CCO.0000000000000180. Review. — View Citation

Volpato LE, Silva TC, Oliveira TM, Sakai VT, Machado MA. Radiation therapy and chemotherapy-induced oral mucositis. Braz J Otorhinolaryngol. 2007 Jul-Aug;73(4):562-8. Review. — View Citation

Wang YM, Jin BZ, Ai F, Duan CH, Lu YZ, Dong TF, Fu QL. The efficacy and safety of melatonin in concurrent chemotherapy or radiotherapy for solid tumors: a meta-analysis of randomized controlled trials. Cancer Chemother Pharmacol. 2012 May;69(5):1213-20. doi: 10.1007/s00280-012-1828-8. Epub 2012 Jan 24. Review. — View Citation

Zhang HM, Zhang Y. Melatonin: a well-documented antioxidant with conditional pro-oxidant actions. J Pineal Res. 2014 Sep;57(2):131-46. doi: 10.1111/jpi.12162. Epub 2014 Aug 6. Review. — View Citation

Zisapel N. [Controlled release melatonin (Circadin) in the treatment of insomnia in older patients: efficacy and safety in patients with history of use and non-use of hypnotic drugs]. Harefuah. 2009 May;148(5):337-41, 348. Review. Hebrew. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in severity of oral mucositis at different time points along the study	Oral mucositis will be evaluated by the World Health Organization (WHO) scale which record the extent and severity of oral mucositis at the third and sixth week after the first radiotherapy session.; This scale combines both subjective and objective measures of oral mucositis.; World Health Organization (WHO) scale for oral mucositis: Grade 0 = No oral mucositis; Grade 1 = Erythema and Soreness; Grade 2 = Ulcers, able to eat solids; Grade 3 = Ulcers, requires liquid diet (due to mucositis); Grade 4 = Ulcers, alimentation not possible (due to mucositis)	up to 3 and 6 weeks
Primary	Changes in the total antioxidant capacity (TAC) in saliva at different time points along the study	TAC is an index that measures total capacity of antioxidants in biological fluids using Colorimetric Method. it can evaluate the antioxidant response against the free radicals produced by radiotherapy.; Normal reference values for TAC in saliva: 0.3-1 mM/L Higher values than normal range indicate higher level of TAC; Changes in the total antioxidant capacity were evaluated at the first day of radiotherapy session (baseline) and six weeks later	Baseline (day 0) and up to 6 weeks
Secondary	Pain and discomfort severity at different time points along the study: Numeric Rating Scale	Discomfort and pain severity were reported by each patient using Numeric Rating Scale (NRS) at the third and sixth week after the first radiotherapy session.; The NRS was calibrated from 0 to 10 with ranges tagged as; No pain (NRS 0); Mild pain (NRS 1-3); Moderate pain (NRS 4-7); Unbearable pain (NRS 8-10)	up to 3 and 6 weeks

External Links

•   WHO Handbook for Reporting Results of Cancer Treatment