Evaluation of Memantine’s Effect on Symptom Characteristics, Neuro-Cognitive Functioning and Neuronal Networks Organization in Patients with Obsessive-Compulsive Disorder: A Randomized, Double-blind, Placebo-Controlled Clinical Trial with Parallel Design

Evaluation of Memantine’s Effect on Symptom Characteristics, Neuro-Cognitive Functioning and Neuronal Networks Organization in Patients with Obsessive-Compulsive Disorder

Randomized, placebo-controlled, double-blind clinical trial

This study will be conducted in a randomized double-blind clinical trial setting at Jami Neuropsychiatry Clinic and National Brain Mapping Laboratory, within the determined temporal duration.

Patients with Obsessive-Compulsive Disorder/ Definitive diagnosis of obsessive-compulsive disorder based on the psychiatrist assessment and its confirmation according to SCID-5 (Structured-Clinical Interview for DSM5) by the clinical psychologist, Y-BOCS Score equal or more than 16 for obsessions and compulsions or equal or more than 10 only for obsessions or compulsions, within the age range of 18-50 years old will be included. Subjects with major depressive disorder, bipolar disorder, personality disorder, and schizophrenia in a way that questions the diagnose of obsessive-compulsive disorder, past or current drug/alcohol abuse or dependence, previous exposure to any kind of psychotropic medication (benzodiazepines, antipsychotics, antidepressants, stimulants, mood stabilizers), past or current neurological disorders (Seizures, Epileptic Syndromes, Head Trauma, Stroke, Loss of consciousness), and other severe internal and surgical disorders will not be included.

Two intervention groups: add-on Memantine and add-on Placebo

1) Symptom (Obsession and Compulsions) Severity Based on Yale Brown Obsessive Compulsive Disorder Scale. 2) Response rate to Memantine treatment based on Yale Brown Obsessive Compulsive Disorder Scale

The reason for the updating is to make changes to the design of the clinical trial; In the previous mode, the parallel design was considered, and in the current edited mode, the parallel design is considered. Since the start of the project, a small number of study subjects have reached the middle weeks of assessment / intervention, and data analysis from neuroimaging (secondary outcome variable) and cognitive assessment (secondary outcome variable) have also begun. The results have indicated that the evaluation of the neurocognitive response / non-response pattern to treatment in sequential parallel design with current number and form of participation during the existing pandemic condition (this study is for people with obsessive-compulsive disorder) is very complex and valid interpretation is hard to provide; Switching to parallel design can solve this problem. In addition, after a statistical review, it was found that due to the greater probability of attrition and excluding from the project by the study subjects in Covid conditions, the implementation of sequential parallel design with respect to the primary and secondary outcome variables, will face with many difficulties. In this edited version, the sections related to the intervention groups have been changed. The other components and dimensions of the project, including all pre-/post study evaluations, the considerations of the execution of the work and the frequency and form of sampling are as stated in the approved draft.

Randomization process will be done using permuted block randomization with blocks in size 4. Regarding determined sample size 48و, quadratic blocks will be produced using the online website: www.sealedenvelope.com. Unique code will be used to apply the allocation concealment to drug boxes, and the code will also be generated by the software. As each individual enters the study based on the sequence generated, the drug box in which the code in question is assigned will be assigned to the individual.

Since the current study will be performed within the neuropsychiatry context and the probability of bias formation and placebo effects are considerable,the subjects and the main investigator that is assessor and also the author of the manuscript would be held blinded. such a way that, the primary neuro-psychological assessments will be executed by the trained clinical psychologist. Staff responsible for preparation of trial medications and randomization process were not further involved in the study.

Information of the main (primary outcome) and the secondary outcomes like neurocognitive functioning and neuronal networks reorganization outcome could be shared.

6 months after publication of results

Research data will be available for the researchers of universities and scientific institutes and also relevant investigators of the industries.

The data will be available, when the samples are taken out, all the stages of the project are completed and finalized, and the results are published.

1. Dr Mahmoudreza Hdjighassem First Address: Neuroscience Group, Reihaneh Department, Keshavarz BLVD, Imam Khomeini Hospital Complex. Tehran. Second Address: 87, School of Advanced Technologies in Medicine, Italia st, Keshavarz blv. Tehran. Cell Phone Number: 09126779102 Faculty Phone Number: 02143052000 Fax Number: 02188991117 Email Address: mhadjighassem@tums.ac.ir 2. Lida Shafaghi Address: 87, School of Advanced Technologies in Medicine, Italia st, Keshavarz blv. Tehran. Cell Phone Number: 09123832340 Fcaulty Number: 0214305200 Email Address: Lidashafaghi@gmail.com

In order to receive the information, firstly the applicants send the formal application to the correspondent of the present proposal, Dr. Hadjighassem (Associate Professor of the Department of Neuroscience and Addiction studies, School of Advanced Technologies in Medicine) and then they will be informed of the details of the data reception (including timing-that will be tried to be within the shortest possible interval- and the way of the addressing the available data like email or in person.