The Effect of Alpha Lipoic Acid on the Incidence and Severity of Radiotherapy-Induced Oral Mucositis in Head and Neck Cancer Patients

Radiation-Induced Mucositis Clinical Trial

Official title:

The Effect of Alpha Lipoic Acid on the Incidence and Severity of Radiotherapy-Induced Oral Mucositis in Head and Neck Cancer Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05023863
• Other study ID #: PHLCLINICAL
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: September 1, 2021
• Est. completion date: August 2022

Study information

• Verified date: August 2021
• Source: Ain Shams University
• Contact: Bishoy Anwar Rizk-Allah, bachelor
• Phone: 01228016836
• Email: bishoyanwar.rezk[@]pharma.asu.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A prospective, randomized, controlled, single-blinded study will be conducted at Clinical Oncology department, Ain Shams University Hospitals, assessing the effect of Alpha Lipoic Acid on the incidence and severity of radiotherapy induced oral mucositis in Head and Neck cancer patients.

Description:

All patients presenting to the Clinical Oncology department, Ain Shams University Hospitals, will be assessed for eligibility as follow:

Inclusion criteria:

• Age >18 years.

• Diagnosis of stage I, II, III or IV squamous cell carcinoma, nasopharyngeal carcinoma.

• Measurable disease on CT scan at baseline.

• Planned to receive radiotherapy with a total dose 60 grays or more divided on 30 fractions with or without cisplatin (100 mg/m2, administered intravenously every 21 days for three cycles or 40 mg/m2 administered weekly for up to 7 weeks).

• Adequate liver function (liver transaminases level < 3 times upper normal limits and total bilirubin < 1.5 times upper normal limits).

• Adequate kidney function (estimated glomerular filtration rate >60 ml/min).

• Adequate bone marrow function (WBCs count > 3000 cells/mm3, ANC count >1500 cells/mm3 and platelets count > 100,000 cells/mm3).

Exclusion criteria:

Patients will be excluded if they have any of the following:

• Diagnosis of Thyroid cancer.

• Presence of other primary cancers.

• Treatment with alpha lipoic acid for any other indication.

• Allergy to alpha lipoic acid.

• Pregnant or lactating women. Eligible patients will be randomized to either… Alpha Lipoic Acid Group (intervention group): 35 patients will receive radiation therapy with or without platinum-based chemotherapy in addition to alpha lipoic acid 600 mg tablets twice daily (throughout the radiotherapy period). The medication will be brought from EVA company ( an Egyptian drug company ) under the trade name of thiotacid 600 mg tablets.

Control Group: 35 Patients will receive radiation therapy with or without platinum-based chemotherapy plus placebo tablets of thiotacid throughout the radiation period

All patients will be followed up weekly to assess the incidence and severity of radiation induced oral mucositis using the radiotherapy oncology group criteria also blood samples will be drawn at baseline , after three weeks (middle of radiation period) at the end of radiation period to asses changes in CRP and TAC levels

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 70
• Est. completion date: August 2022
• Est. primary completion date: May 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• • Age >18 years.

• Diagnosis of stage I, II, III or IV squamous cell carcinoma, nasopharyngeal carcinoma.

• Measurable disease on CT scan at baseline.

• Planned to receive radiotherapy with a total dose 60 grays or more divided on 30 fractions with or without cisplatin (100 mg/m2, administered intravenously every 21 days for three cycles or 40 mg/m2 administered weekly for up to 7 weeks).

• Adequate liver function (liver transaminases level < 3 times upper normal limits and total bilirubin < 1.5 times upper normal limits).

• Adequate kidney function (estimated glomerular filtration rate >60 ml/min).

• Adequate bone marrow function (WBCs count > 3000 cells/mm3, ANC count >1500 cells/mm3 and platelets count > 100,000 cells/mm3).

Exclusion Criteria:

• ? Diagnosis of Thyroid cancer.

• Presence of other primary cancers.

• Treatment with alpha lipoic acid for any other indication.

• Allergy to alpha lipoic acid.

• Pregnant or lactating women.

Related Conditions & MeSH terms

• Head and Neck Neoplasms
• Mucositis
• Radiation-Induced Mucositis
• Stomatitis

Intervention

Drug:
• Alpha Lipoic Acid 600 MG Oral Tablets
Alpha Lipoic Acid (ALA) is a drug which has been used in treatment of diabetic neuropathy . It act through enhancing nitric oxide-mediated endothelium-dependent vasodilation, thus improving microcirculation in patients with diabetic polyneuropathy. It is considered a safe drug, generally with a daily dose of 200 to 2400 mg/day is considered tolerable without significant side effects. Only gastrointestinal tracts side effects like nausea, vomiting, dyspepsia and abdominal pain have been described in some clinical trials. Also FDA experts confirm its safety and efficacy in humans

Other:
• Placebo tablets
placebo tablets of the same generic of active drug which contain all the same ingredients as active tablets except alpha lipoic acid

Radiation:
• radiation or concurrent chemoradiation
radiation or concurrent radiotherapy plus platinum-based chemotherapy

Locations

Country	Name	City	State
Egypt	Ain Shams University	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

References & Publications (20)

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Elsabagh HH, Moussa E, Mahmoud SA, Elsaka RO, Abdelrahman H. Efficacy of Melatonin in prevention of radiation-induced oral mucositis: A randomized clinical trial. Oral Dis. 2020 Apr;26(3):566-572. doi: 10.1111/odi.13265. Epub 2020 Jan 15. — View Citation

Gillison ML. Human papillomavirus-related diseases: oropharynx cancers and potential implications for adolescent HPV vaccination. J Adolesc Health. 2008 Oct;43(4 Suppl):S52-60. doi: 10.1016/j.jadohealth.2008.07.002. Review. — View Citation

Jung JH, Jung J, Kim SK, Woo SH, Kang KM, Jeong BK, Jung MH, Kim JH, Hahm JR. Alpha lipoic acid attenuates radiation-induced thyroid injury in rats. PLoS One. 2014 Nov 17;9(11):e112253. doi: 10.1371/journal.pone.0112253. eCollection 2014. Erratum in: PLoS One. 2015;10(6):e0131147. — View Citation

Kim H, Yoo WS, Jung JH, Jeong BK, Woo SH, Kim JH, Kim SJ. Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling. Int J Mol Sci. 2019 Nov 13;20(22). pii: E5691. doi: 10.3390/ijms20225691. — View Citation

Kim JH, Jeong BK, Jang SJ, Yun JW, Jung MH, Kang KM, Kim TG, Woo SH. Alpha-Lipoic Acid Ameliorates Radiation-Induced Salivary Gland Injury by Preserving Parasympathetic Innervation in Rats. Int J Mol Sci. 2020 Mar 25;21(7). pii: E2260. doi: 10.3390/ijms21072260. — View Citation

Kusiak A, Jereczek-Fossa BA, Cichonska D, Alterio D. Oncological-Therapy Related Oral Mucositis as an Interdisciplinary Problem-Literature Review. Int J Environ Res Public Health. 2020 Apr 3;17(7). pii: E2464. doi: 10.3390/ijerph17072464. Review. — View Citation

Logan RM, Stringer AM, Bowen JM, Gibson RJ, Sonis ST, Keefe DM. Serum levels of NFkappaB and pro-inflammatory cytokines following administration of mucotoxic drugs. Cancer Biol Ther. 2008 Jul;7(7):1139-45. Epub 2008 Apr 29. — View Citation

Lott IT, Doran E, Nguyen VQ, Tournay A, Head E, Gillen DL. Down syndrome and dementia: a randomized, controlled trial of antioxidant supplementation. Am J Med Genet A. 2011 Aug;155A(8):1939-48. doi: 10.1002/ajmg.a.34114. Epub 2011 Jul 7. — View Citation

Mallick S, Benson R, Rath GK. Radiation induced oral mucositis: a review of current literature on prevention and management. Eur Arch Otorhinolaryngol. 2016 Sep;273(9):2285-93. doi: 10.1007/s00405-015-3694-6. Epub 2015 Jun 27. Review. — View Citation

Marur S, Forastiere AA. Head and Neck Squamous Cell Carcinoma: Update on Epidemiology, Diagnosis, and Treatment. Mayo Clin Proc. 2016 Mar;91(3):386-96. doi: 10.1016/j.mayocp.2015.12.017. Review. — View Citation

Moreira PI, Harris PL, Zhu X, Santos MS, Oliveira CR, Smith MA, Perry G. Lipoic acid and N-acetyl cysteine decrease mitochondrial-related oxidative stress in Alzheimer disease patient fibroblasts. J Alzheimers Dis. 2007 Sep;12(2):195-206. Review. — View Citation

Pearman TP, Beaumont JL, Paul D, Abernethy AP, Jacobsen PB, Syrjala KL, Von Roenn J, Cella D. Evaluation of treatment- and disease-related symptoms in advanced head and neck cancer: validation of the national comprehensive cancer network-functional assessment of cancer therapy-head and neck cancer symptom index-22 (NFHNSI-22). J Pain Symptom Manage. 2013 Jul;46(1):113-20. doi: 10.1016/j.jpainsymman.2012.06.004. Epub 2012 Sep 25. — View Citation

Reljanovic M, Reichel G, Rett K, Lobisch M, Schuette K, Möller W, Tritschler HJ, Mehnert H. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy. Free Radic Res. 1999 Sep;31(3):171-9. — View Citation

Sayed R, El Wakeel L, Saad AS, Kelany M, El-Hamamsy M. Pentoxifylline and vitamin E reduce the severity of radiotherapy-induced oral mucositis and dysphagia in head and neck cancer patients: a randomized, controlled study. Med Oncol. 2019 Nov 21;37(1):8. doi: 10.1007/s12032-019-1334-5. — View Citation

Siddiqui F, Movsas B. Management of Radiation Toxicity in Head and Neck Cancers. Semin Radiat Oncol. 2017 Oct;27(4):340-349. doi: 10.1016/j.semradonc.2017.04.008. Review. — View Citation

Sonis ST. Pathobiology of oral mucositis: novel insights and opportunities. J Support Oncol. 2007 Oct;5(9 Suppl 4):3-11. Review. — View Citation

Ziegler D, Nowak H, Kempler P, Vargha P, Low PA. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis. Diabet Med. 2004 Feb;21(2):114-21. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of radiation induced oral mucositis	The patients will be followed up during the whole period of radiation and up to six weeks after radiation to evaluate the incidence and severity of radiation induced mucositis. Severity will be assessed by the oncologist using radiotherapy oncology group criteria (RTOG criteria)	4 months
Secondary	Time to develop grade III or IV radiation induced oral mucositis:	For each patient, the time from the start of radiotherapy till the development of grade III or IV RIOM will be recorded.	4 months