Evaluation of Clozapine-Induced Immunodeficiency in Patients with Parkinson's Disease: A Study on Serum IgG Level Variation

The primary objective of this study is to evaluate the variation in the **serum IgG level** reflecting the humoral immune response six months after the initiation of treatment with **Clozapine** in patients with **Parkinson's disease**. This is clinically relevant as it aims to assess the potential immunodeficiency effects associated with Clozapine, which could impact the management and therapeutic strategies for patients with Parkinson's disease.

Secondary objectives include assessing various clinical and laboratory parameters:

• Patient weight
• Infections presented by the patient
• Use of antibiotics by the patient
• Tolerance and adverse effects of treatment with Clozapine
• Motor state, quality of life, depressive syndrome, apathy, global cognitive efficiency, and psychotic elements
• Serum IgA, IgM, and IgG levels, including IgG subclasses (IgG1, IgG2, IgG3, IgG4)
• Complete blood count (CBC) parameters
• C-reactive protein levels
• Serum Clozapine level
• T, B, and NK lymphocyte subpopulations

The clinical trial involves participants diagnosed with **Parkinson's disease** who are 18 years of age or older. Both male and female subjects are included in the study, and the trial does not specifically target a vulnerable population. The participants are required to exhibit psychotic symptoms necessitating the initiation of treatment with Clozapine. The sponsor has not provided information regarding the total number of participants. The selection of the trial population is based on the presence of Parkinson's disease and the need for Clozapine treatment, without specific lifestyle considerations such as diet or physical activity being highlighted. The study aims to evaluate the variation in serum IgG levels, reflecting the humoral immune response, six months after starting treatment with Clozapine.

The clinical trial is designed to evaluate the **variation in serum IgG levels** reflecting the humoral immune response in patients with **Parkinson's disease** following treatment with **Clozapine**. This is a Phase IV, low-intervention trial, characterized by a randomized, double-blind, controlled design. The trial is expected to commence on September 1, 2024, and conclude by September 1, 2027, with a total duration of 36 months. Participants will be involved for a maximum treatment period of 12 months, during which they will receive **Clozapine** orally, with a maximum daily dose of 75 mg and a total dose not exceeding 900 mg.

The study will include several key visits: an initial screening visit (D0), follow-up visits at 6 months (M6), and 12 months (M12), and an end-of-study visit. The primary endpoint is the change in serum IgG levels before and 6 months after the initiation of treatment. Secondary endpoints include variations in weight, infection rates, antibiotic use, and tolerance/adverse effects of **Clozapine**. Additionally, changes in motor status, quality of life, depressive symptoms, and cognitive efficiency will be assessed using clinical scales such as MDS-UPDRS, PDQ39, and MoCA. Blood tests will be conducted to evaluate variations in serum IgA, IgM, IgG subclasses, CBC parameters, CRP levels, and lymphocyte subpopulations.

Participants must be 18 years or older, diagnosed with **Parkinson's disease**, and exhibit psychotic symptoms necessitating **Clozapine** treatment. Conditions for early termination from the study include non-compliance with the protocol, adverse reactions to the medication, or withdrawal of consent. The trial aims to provide comprehensive data on the immunological and clinical effects of **Clozapine** in this patient population.

The clinical trial involves the administration of **Clozapine**, an experimental medication, to evaluate its effects on immunodeficiency in patients with Parkinson's disease. **Clozapine** is provided in the form of a **tablet** and is administered orally. The dosing regimen for this trial specifies a maximum daily dose of 75 mg, with a total maximum dose not exceeding 900 mg over the course of the treatment. The treatment period is set for a maximum of 12 months. The primary objective of the trial is to assess the variation in serum IgG levels, which reflect the humoral immune response, six months after the initiation of treatment with **Clozapine**.

In this study, **Clozapine** is the sole investigational product, and no additional non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized. The trial does not involve any pediatric formulations, and the medication is classified as a chemical product. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial does not involve any devices or other medicinal products beyond the administration of **Clozapine**.

The clinical trial aims to assess the efficacy of Clozapine in patients with Parkinson's disease by evaluating the variation in serum **IgG** levels, which reflects the humoral immune response. The primary endpoint is the change in serum IgG levels measured before the initiation of treatment and six months after starting Clozapine. Secondary endpoints include variations in the patient's weight, the number of infections, antibiotic use, and tolerance or adverse effects of Clozapine, all collected during visits at months 6 and 12. Additionally, changes in motor status, quality of life, depressive syndrome, apathy, global cognitive efficiency, and psychotic elements will be assessed using clinical scales such as MDS-UPDRS, PDQ39, Goldberg, Starkstein, MoCA, and the neuropsychological inventory (NPI) at baseline, month 6, and month 12.

Further secondary endpoints involve variations in serum IgA, IgM, and IgG subclass levels, complete blood count (CBC) parameters, C-reactive protein (CRP) levels, serum Clozapine levels, and T, B, and NK lymphocyte subpopulations, all measured through blood tests at baseline, month 6, and month 12. The trial is categorized as a Phase IV, low-intervention clinical trial, with an estimated recruitment start date of September 1, 2024, and an estimated end date of September 1, 2027. The maximum treatment period for participants is 12 months, with Clozapine administered orally in tablet form.