2.4. Interventions

Lactobacillus plantarum PS128 (PS128), which was isolated from a traditional Taiwan fermented mustard food [17], was deposited under DSMZ Accession No. DSM 28632. The genome architecture of PS128 was illustrated [18]. Both animal and human studies with PS128 demonstrated great safety [5,12,13,19]. The probiotic capsule contained only PS128 as a single-strain probiotic. Dosage in the study was 2 capsules a day (6 × 10¹⁰ CFUs). Microcrystalline cellulose capsules were used as a placebo for PS128. Both probiotics and placebo capsules were free gifts obtained from Bened Biomedical Co., Ltd (Taipei, Taiwan).

In this study, oxytocin was administered nasally. The Syntocinon^® Spray (Novartis Pharma AG; purchased from Apotheke Roter Ochsen, Schaffhausen, Switzerland and Victoria Apotheke Wholesale, Schwerzenbach, Switzerland) is currently the most commonly used standardized oxytocin nasal spray for clinical trials worldwide. We instructed the patient and family members about the use of this spray. Dosing began with 1 puff of 4 IU daily for the first week of the second stage. Subsequently, the dosage was increased to 1 puff per nostril daily (8 IU/d) for the second week and 1 puff per nostril twice a day (16 IU/d) for the third week. The dosage was then titrated up to the maximum dose of 32 IU daily, which is 2 puffs per nostril twice a day, starting on the fourth week. The dosage of 32 IU per day has been approved as safe and adequate in even younger patients (age 3–8 years) by a previous publication [20]. Another study reported a 4-week intranasal OXT treatment (24 IU, twice daily with total 48IU per day, which is more than the max dose in this study of 32 IU per day) in 32 children with ASD, aged 6–12 years old [21]. We achieved an active IND from the FDA, and the IND number is 138827 for Syntocinon^® (Pitocin, Oxytocin).