Efficacy of combined administration of Baekhogainsam-Tang and low-dose pilocarpine on frequent intractable xerostomia: study protocol for a multi-center randomized controlled trial

Abstract

Abstract Background Intractable xerostomia is defined as the subjective perception of dry mouth and persistent salivary gland hypofunction even after attempting treatment. Pilocarpine is an effective salivary sialagogue; however, it often exhibits more side effects at high doses and limited effectiveness at low doses. Baekhogainsam-Tang (BIT) is a common herbal formula used by patients complaining of sore throats and thirst. Several studies have reported that BIT increases salivary gland secretion and improves dry mouth symptoms without significant side effects. However, no clinical trials have studied the efficacy of the combined administration of BIT and low-dose pilocarpine for intractable xerostomia. Therefore, we aim to assess the non-inferior efficacy and fewer side effects of the combined administration of BIT and low-dose pilocarpine compared with the administration of only high-dose pilocarpine. Methods A randomized, open-label, parallel-group, multi-center trial will be conducted. A total of 120 patients with Sjogren’s syndrome having an unstimulated salivary flow rate (SFR) ≤ 0.1 mL/min or who have undergone radiotherapy to the head and neck with an unstimulated SFR ≤ 0.25 mL/min will be recruited competitively at four trial centers. They will be randomly allocated to either the experimental or control groups. The experimental group will receive BIT herbal granules three times and pilocarpine (2.5 mg) four times daily; meanwhile, the control group will receive only 5 mg pilocarpine four times daily for 12 weeks. The primary outcome is unstimulated SFR after 12 weeks of treatment. Secondary outcomes are stimulated SFR after 12 weeks of medication, as well as differences and mean percentage changes in unstimulated and stimulated SFR, visual analog scale, salivary scintigraphy, and questionnaires for both oral symptoms and quality of life from baseline to the end of the trial. Discussion This trial will be significant evidence on the efficacy and safety of the combined use of BIT and low-dose pilocarpine to treat intractable xerostomia. Trial registration This trial is registered with the Clinical Research Information Service of the Republic of Korea (ISRCTN, KCT0005982, Registered 10 March 2021).