Evaluation of Ondansetron augmentation therapeutic effectiveness in Obsessive Compulsive disorder patients resistant to treatment by selective serotonin reuptake inhibitor: Double-blind randomized clinical trial with placebo control

Evaluation of the Therapeutic Effect of Adding Ondansetron in Patients with Treatment-Resistant Obsessive-Compulsive Disorder Under Serotonin Reuptake Inhibitor Therapy

Phase 3 randomized, double-blind, parallel-group, controlled clinical trial on 40 patients. Block randomization will be performed, with an allocation ratio of 1:1

Background: At Rasht, Psychiatry Outpatient Clinic; investigating the effect of ondansetron in treatment-resistant Obsessive Compulsive Disorder ,Method: Double-blind, randomized, placebo-controlled.Sample:40 patients divided into two groups of 20(ondansetron vs. placebo).Assessment:Day 0, Week 8, and Week 12, Blinding:Patients, physicians, and outcome assessors are unaware of the intervention

Inclusion: Diagnosis of obsessive-compulsive disorder based on the Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition ,Age range: 18 to 50 years, Total score of the Yale-Brown Obsessive Compulsive Scale above 16, Ventricular electrical interval(QT) less than 420 milliseconds on ECG prior to the start of the study, No history of prolonged ventricular electrical interval syndrome in the patient or their family Exclusion:Active psychosis, Serious medical conditions, Cardiac issues/family history, Substance use, Intellectual disability, Pregnancy/lactation, Concurrent psychotherapy

Intervention Group:4 mg ondansetron,daily manufactured by Sobhan Darou Company for 12 weeks with an serotonin reuptake inhibitor; Control Group: placeb ,daily manufactured by Sobhan Darou Company for 12 weeks with an serotonin reuptake inhibitor

Severity of Obsessive Compulsive Disorder symptom based on the Yale-Brown Obsessive Compulsive Scale

1. Randomization method: Block randomization with an allocation ratio of 1:1 between two groups, with a block size of 4. 2. Unit of randomization: Individual 3. Stratification: Not used. 4. Randomization tool: The random sequence was generated based on the method described in the article with the digital object identifier (DOI) "10.22034/PJMS.2022.700469". The tool used was the Random Allocation Software. Allocation was performed using pre-generated, numbered codes enclosed in sealed opaque envelopes. 5. Sequence generation: The random sequence was generated and maintained by a researcher not involved in data assessment and analysis. 6. Allocation concealment: To maintain allocation concealment, sequentially numbered, sealed, and coded envelopes were used. Patient evaluation and allocation were performed by separate individuals, and treatment information was kept blinded to both the clinical assessor and the patient.

1. Participants (Patients): All participants are unaware of the type of intervention (drug or placebo). The drug and placebo have been prepared to be identical in appearance, color, and packaging. Patients are only aware of their participation in a treatment study but do not know the type of intervention they are receiving. 2. Healthcare Personnel (Faculty Responsible for Patient Visits): Two faculty members responsible for the initial visits and follow-up of patients are unaware of the intervention allocation (drug or placebo) and operate in a blinded manner. 3.Principal Investigator: The principal investigator assigns patients to two groups based on a randomization table at the beginning of the study and is the only person aware of the intervention allocation. They are not blinded. 4. Data Collectors: Study data is collected by the principal investigator. Since they are aware of the intervention type, this phase is conducted in a non-blinded manner. However, structured forms and pre-defined checklists are used to minimize bias. 5. Outcome Assessors: Faculty members responsible for evaluating the response to treatment are unaware of the allocation of patients to either the drug or placebo group. Therefore, outcome assessment is conducted in a blinded manner. 6.Data Safety and Monitoring Committee (DSMC): An independent committee for data safety monitoring has not been established for this study. Safety monitoring and potential adverse events are overseen by the principal investigator, with decisions made in consultation with supervising faculty when necessary. 7. Final Article Author: The final article author is the principal investigator, who is aware of the intervention allocation. However, the data is provided to a statistician in a coded format without reference to the intervention type, ensuring statistical analysis is conducted without knowledge of treatment allocation.

Title of Documents and Study Data: "Investigating the Effect of Ondansetron in Treatment-Resistant OCD: A Phase 3 Clinical Trial" Data Details "Type of Data:Includes primary outcome measures (OCD symptom severity, response to treatment, safety, and tolerability of the drug)" "Data Accessibility: Only anonymized data related to primary outcomes will be available for sharing" "Limitations:Individual participant data will not be disclosed to ensure confidentiality"

Data Access Timeline: "Start Date:6 months after the publication of study results" "Access Duration:Unlimited for anonymized primary outcome data" "Limitations:Individual participant data will not be shared"

Authorized Individuals for Data Access: "Academic and scientific researchers affiliated with reputable research institutes and universities" "Industry professionals in pharmaceutical and healthcare sectors related to clinical research" "Regulatory and medical policy organizations for study result evaluation" Restrictions: "Data will be shared only in anonymized form, and requests must be submitted through official institutions with Ethics Committee approval"

Conditions and Purpose of Data Usage: "Research Purposes: Anonymized data may only be used for scientific studies and statistical analyses related to Obsessive-Compulsive Disorder (OCD)" "Permitted Analyses: Researchers are allowed to perform statistical analyses, clinical modeling, and meta-analyses on the provided data." "Usage Restrictions:Data must not be used for commercial, promotional, or non-scientific purposes." "Regulatory Oversight:Data usage must comply with Ethics Committee approval and confidentiality standards" "Request Submission Requirements: Researchers must submit a formal request through academic or research institutions and sign a data usage agreement"

Guidelines for Requesting Data and Documents: "Priority 1:Official request through the Ethics Committee in Research, Guilan University of Medical Sciences Address:Guilan, Rasht, Guilan University of Medical Sciences, Ethics Committee in Research Email: ethics@gums.ac.ir " " Priority 2:Contact the Study Director or Principal Investigator" "Applicants must submit a formal written request detailing the purpose of data usage and obtain approval from the Ethics Committee."

Process for Requesting and Receiving Data: 1.Submitting an Official Request:The applicant must send a formal written request to the **Ethics Committee at Guilan University of Medical Sciences including the purpose of data usage the type of data required, and their credentials. 2.Review by the Ethics Committee:The request is evaluated for approval or rejection, a process that typically takes 2 to 4 weeks 3.Signing the Data Usage Agreement:If approved, the applicant must sign a confidentiality and data usage agreement before accessing the data. 4.Receiving the Data:Once finalized, anonymized data is shared via email or the research data platform within 1 to 2 weeks Total estimated duration:The process of data access typically takes 4 to 6 weeks depending on review speed.