Evaluation of the Efficacy of Piracetam as an Adjunct to Methylphenidate in the Treatment of Symptoms of Attention-Deficit/Hyperactivity Disorder in Children: A Randomized Double-Blind Clinical Trial

To evaluate the effect of piracetam as an adjunctive therapy to methylphenidate on attention-deficit/hyperactivity disorder (ADHD) symptoms and executive functioning in children attending the Child and Adolescent Psychiatry Outpatient Clinic of Golestan Hospital, Ahvaz.

A phase II, randomized, double-blind, placebo-controlled, parallel-group clinical trial conducted on 48 children with attention-deficit/hyperactivity disorder.Randomization was performed using block randomization using R software.

This randomized, double-blind, placebo-controlled clinical trial will be conducted at the Child and Adolescent Psychiatry Subspecialty Clinic of Golestan Hospital, Ahvaz. Children with ADHD will be randomly assigned to receive methylphenidate plus piracetam or methylphenidate plus placebo. Participants, parents, clinicians, outcome assessors, and data analysts will remain blinded to treatment allocation.

Inclusion Criteria: Children referred to the Child and Adolescent Psychiatry Subspecialty Clinic of Golestan Hospital, Ahvaz, with a diagnosis of ADHD, who do not have any serious medical illness and are not currently receiving medication for ADHD treatment. Exclusion Criteria: Presence of any major psychiatric disorder, such as psychotic disorders or mood disorders, as well as metabolic disorders or chronic underlying medical diseases.

Intervention Group: Participants in this group will receive standard treatment with methylphenidate plus adjunctive piracetam. Control Group: Participants in this group will receive standard treatment with methylphenidate plus placebo instead of piracetam.

Change in attention-deficit/hyperactivity disorder (ADHD) symptoms; change in executive functioning; occurrence of treatment-related adverse effects

Eligible participants will be randomly assigned to the intervention and control groups in a 1:1 allocation ratio using block randomization with variable block sizes of 4 and 6 to maintain balance between the groups throughout the study while minimizing the predictability of treatment allocation. The individual participant is the unit of randomization. Each eligible child will be independently assigned to one of the two study groups. Stratified randomization will not be used in this study. The randomization sequence will be generated using R software and randomizer package which is develped to help randomization in clinical trials, and this will be generated by an independent researcher who is not involved in participant recruitment, treatment administration, or outcome assessment. The allocation sequence will be kept in sequentially numbered, opaque, sealed envelopes (SNOSE). The allocation sequence will be generated using a computer-generated random number algorithm based on permuted block randomization with variable block sizes of 4 and 6 and a 1:1 allocation ratio. The sequence will remain concealed until the time of participant assignment. Allocation concealment will be ensured using sequentially numbered, opaque, sealed envelopes (SNOSE) containing the treatment assignments. After confirming eligibility and obtaining written informed consent, the next envelope in sequence will be opened by a designated individual responsible for dispensing the study medication. Investigators, participants, parents or legal guardians, treating physicians, and outcome assessors will remain blinded to treatment allocation throughout the study.

To maintain blinding, piracetam and placebo will be identical in appearance, color, size, packaging, and labeling, and will be identified only by study codes. Participants and their parents/legal guardians will be blinded to the treatment allocation. The treating child and adolescent psychiatrist and the principal investigator, who are responsible for clinical evaluation and patient follow-up, will remain blinded to group assignment throughout the study. Outcome assessors and data collectors will also be blinded to treatment allocation. The statistical analyst will analyze the data using coded treatment groups (e.g., Group A and Group B) and will remain blinded to the treatment assignments until completion of the primary statistical analysis. Only the independent researcher responsible for generating the randomization sequence and preparing/dispensing the coded study medications will have access to the allocation codes. This individual will have no role in participant recruitment, clinical assessment, outcome evaluation, or data analysis. The allocation codes will remain confidential until completion of data collection and the primary statistical analysis. Emergency unblinding will be permitted only when knowledge of the assigned treatment is essential for the clinical management and safety of a participant.

All data can potentially be shared after de-identifying individuals.

Access period begins 2 months after publication of results.

Researchers employed at academic and scientific institutions

Research purposes

ali.vz.ali@gmail.com +989213659375 Ali Vaziri Esfarjani

Coordination with the university and relevant faculty must be carried out first