## 2 Materials and Methods  
We conducted a prospective, interventional, single-center, double-blinded, parallel-armed, placebo-controlled, and split-mouth designed, randomized feasibility clinical trial. The study protocol was conducted according to the guidelines of the Declaration of Helsinki of 1975, revised in 2013, and approved by both the Istanbul Medipol University Clinical Research Ethics Committee (Number: E-66291034-604.01.01-2798, Date: 15 June 2021) and the Turkish Medicine and Medical Devices Agency (Number: E-68869993-511.06-491724, Date: 28 July 2021). Written informed consent, including the study protocol and information that the study would be published in an international journal, was obtained from all participants at the beginning of the study. A total of four eligible participants diagnosed according to the new classification framework proposed by the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions [15; 16; 17] were recruited from the Faculty of Dentistry, Department of Periodontology in Istanbul, Turkey, between August and October 2021. Participants who satisfied the following criteria were included in the trial: age between 18 and 65 years; willingness to use only oral care products provided by the investigators during the trial; adverse history of any infectious or systemic disease; negative history of allergy to persulfates; non-smokers and non-drinkers; having more than 20 teeth; and no previous treatment for periodontitis and gingivitis. Participants with the following characteristics were excluded from the trial: age under 18 or over 65 years; pregnant or lactating females; history of systemic or infectious disease; history of allergy to NitrAdineTM; smoking or use of tobacco in any form; alcoholism; the use of antibiotics and anti-inflammatory drugs within six months prior to the start of the trial; fewer than 20 teeth; the use of orthodontic appliances or removable prosthetic appliances; and the use of daily chemical plaque inhibitors or mouthwash. In August 2021, all of the patients referred to the clinic were screened, and potential volunteers who met the inclusion criteria were identified. The written informed consent form, which included information about the purpose of the trial, the procedures to be carried out, and the participant's rights, was signed by all participants prior to their enrollment in the trial. This trial was designed for participants suffering from different periodontal diseases. Two participants diagnosed with gingivitis on an intact periodonotinum associated with dental biofilm (G) and two participants diagnosed with stage III grade B generalized periodontitis (P) were recruited for the trial. The participants received either NitrAdineTM (PerioTabsR), Bonyr AG, Yaduz, Liechtenstein) or placebo, and half the mouth was randomly exposed to therapeutic (NitrAdineTM/placeb treatment after SRP) or prophylactic intervention (NitrAdineTM/placeb treatment before SRP). At the first appointment, intraoral photos were made, clinical periodontal parameters including plaque index (PI) [18], gingival index (GI) [19], probing depth (PD), bleeding on probing (BOP), gingival recession, and clinical attachment level (CAL) were recorded from six sites (disto-buccal, mid-buccal, meso-buccal, disto-palatal, mid-palatal, and meso-palatal) around each tooth using [PERSON]'s periodontal probe (Hu-Friedy, Chicago, IL, USA) immediately before SRP. Oral hygiene instruction was demonstrated via a modified [PERSON]'s brushing technique and an interdental brush using a cast model. SRP was performed on half of the mouth randomly, which had been divided into the right and left quadrants. After SRP, randomized NitrAdineTM or placebo effervescent tablets were used to brush the teeth and gums for 2 min, once a day, for 10 days. Intraoral photos and clinical periodontal parameters were recorded at baseline (day 0), immediately prior to any treatment, on day 11, subsequent to SRP and effervescent tablets application, and on day 40, the end of the trial.