Comparing the effect of probiotics with placebo on xerostomia in head and neck cancer patients undergoing radiation therapy

Comparison of unstimulated saliva flow in two probiotic and placebo groups Comparing the amount of stimulated saliva flow in two probiotic and placebo groups Comparison of dry mouth severity score (VAS) in two probiotic and placebo groups

A controlled randomized trial, double blinded with a parallel group design of 82 patients (Phase 3). Randomization will be used by PASS program.

This study is conducted on patients with head and neck cancer who underwent radiotherapy in the last 1-3 months. After obtaining informed consent, these patients who referred to the Razi or Amiralmomenin Hospitals in Rasht will be enrolled. Patients are randomly assigned to one of the two intervention or control groups and receive the corresponding code inside the sealed envelope and receive the corresponding drug from the hospital pharmacist.

Inclusion criteria: All head and neck cancer patients who have had 1-3 months of radiotherapy; A functional level equal to or higher than 80 according to the Karnovsky criterion Non-entry criteria: Any other type of oral disease; Inability to understand the questionnaire; Parkinson; Sjogren; Diabetes; Acquired immunodeficiency syndrome; Use of drugs affecting saliva; Pregnancy; Taking antibiotics or probiotics in the last month

The particpants of the intervention group receives a Lactogum troche before going to bed for 60 days. The mentioned drug is a product of Zist Takhmir company and contains the probiotic K12 and M18 strain of Streptococcus salivarius. The participants of the control group receives a placebo lozenge before going to bed for 60 days. The placebo is similar to Lactogum troche, but it does not contain probiotics.

volume of unstimulated saliva volume of stimulated saliva severity of xerostomia ( Visual Analog Scale; VAS)

In the initial version of the protocol, the sample size was estimated using G*Power based on an independent two-sample t-test, resulting in 64 participants per group. After a methodological revision and considering the correlated and serial structure of the continuous data, the statistical analysis was modified to a serial correlation model, which better aligns with the temporal nature of the data and the study objectives. Accordingly, the sample size was recalculated in G*Power and reduced to 41 participants per group (with 80% power and a 0.05 significance level). This change was made to improve statistical precision and ensure better alignment with the final analysis approach, without affecting the scientific validity of the study. It is also noted that this modification has been approved by the university’s research committee

A statistician will generate independent allocation sequences and randomisation lists using the Power Analysis & Sample Size (PASS) software. Randomization will be performed in blocks of 4 (2 placebo and 2 probiotic) (21 blocks). To ensure allocation concealment, an independent person will oversee the packaging and labelling of trial treatments based on the randomisation schedule at otorhinolaryngology research center of Guilan University of Medical Sciences (GUMS). Zist Takhmir company (Tehran, Iran) provides the probiotic and placebo; the group assignment list will be withheld until the final evaluation of the study data. All investigators, participants, and outcome assessors will be blinded to the assigned treatment throughout the study.

Probiotics and placebo are prepared by Zyst Takhmir and are similar in terms of color, size and dimensions and packages. All the following drugs have a special code and are given to patients by the hospital pharmacist based on the assigned code in the randomization process. Patients and researchers and people who evaluate the results will not know about the type of intervention.

In the case of individual patient data, all potential data will be shared after de-identifying individuals. The result of the clinical study will be published in the form of an article.

The access period starts 6 months after publication of the results.

All researchers

For secondary data analysis and meta-analysis

Dr Mir Mohammad Jalali Otorhinolaryngology research center, Amiralmomenin HospitalAmiralmomenin Hospital,17 sharivar street, Bank Mell square, Rasht , Iran. 4139638459 Tel: 0098 13 33238306 Mobile: 0098 9111318776 Email: mmjalali@gmail.com

After receiving the applicant's request and a brief statement of the protocol in which the mentioned information is used, a preliminary review will be done and the information will be sent to the researcher within 2 weeks.