Efficacy of Choline Alfoscerate in Subthreshold Depression Among Elderly Patients: A Pilot Study

The primary objective of this study is to evaluate the **efficacy** of choline alfoscerate in treating subthreshold depression in elderly patients. This is clinically relevant as subthreshold depression, often underdiagnosed, can significantly impact the quality of life and cognitive function in the elderly population. Addressing this condition with effective treatment could improve mental health outcomes and overall well-being in this demographic.

The secondary objectives of the study are:

• To evaluate whether choline alfoscerate can determine a specific improvement in the cognitive symptoms associated with subthreshold depression.
• To evaluate whether choline alfoscerate can lead to a specific improvement in apathy associated with subthreshold depression.

The clinical trial focuses on evaluating the efficacy of **choline alfoscerate** in elderly patients experiencing subthreshold depression. The study population includes both male and female participants aged 65 years and older. Participants are required to exhibit between two to four depressive symptoms for at least two weeks prior to enrollment. The trial does not involve a vulnerable population. Participants must have a Mini-Mental State Examination (MMSE) score of 24 or higher and a Montreal Cognitive Assessment (MOCA) score of less than 26. The sponsor has not provided information regarding the total number of participants. All participants must be capable of understanding and signing informed consent. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that participants are cognitively capable of providing informed consent and are experiencing a specific level of depressive symptoms, aligning with the study's objective to assess treatment efficacy in this demographic.

The clinical trial is designed to evaluate the efficacy of **choline alfoscerate** in treating subthreshold depression in elderly patients. This study is a **randomized**, **double-blind**, and **controlled** trial, ensuring that neither the participants nor the researchers know who is receiving the treatment or placebo, thus minimizing bias. The trial is categorized as a Phase IV study, indicating it is conducted after the product has been marketed to gather additional information on the drug's effect in a larger population. The trial is expected to last until June 30, 2025, with recruitment having started on September 1, 2021.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on criteria such as age (≥65 years), presence of 2 to 4 depressive symptoms for at least two weeks, and cognitive assessments like the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA). Following the screening, eligible participants will be enrolled and randomly assigned to receive either the active treatment, **GLIATILIN 600 capsule**, or a placebo. The treatment will be administered orally, with a maximum daily dose of 1200 mg over a period of up to 8 weeks.

Throughout the trial, participants will attend follow-up visits to monitor their response to the treatment and any adverse effects. The primary endpoint will be assessed by analyzing changes from baseline in the Hamilton Depression Rating Scale-17 items (HAMD-17) at the final visit. Secondary endpoints include evaluating changes in depression symptoms using the Geriatric Depression Scale-15 items (GDS-15) and Clinical Global Impression-severity (CGI-s), as well as cognitive symptoms using the MOCA scale.

The expected length of participant involvement is approximately 8 weeks, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include significant adverse reactions, withdrawal of consent, or any other medical reasons deemed necessary by the investigator. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted to evaluate the overall efficacy and safety of the treatment.

The clinical trial involves the administration of **choline alfoscerate** as the experimental medication. The product used is marketed under the name **GLIATILIN 600 capsule**, which is a **soft capsule** formulation. Each capsule contains 600 mg of the active substance, **choline alfoscerate**, which is of chemical origin. The medication is administered orally, with a maximum daily dose of 1200 mg, equating to two capsules per day. The total maximum dose over the course of the study is 76800 mg. The treatment period is set for a maximum of 8 weeks. The product is manufactured by ITALFARMACO S.P.A and is not a paediatric formulation. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified for use in this study. The focus remains solely on evaluating the efficacy of **choline alfoscerate** in addressing subthreshold depression in elderly patients. The study does not involve any additional medicinal products or devices. The trial is designed to assess the primary objective of determining the effectiveness of the experimental medication in the specified patient population.

The efficacy of **choline alfoscerate** in treating subthreshold depression in elderly patients will be assessed through a series of validated scales. The primary endpoint involves evaluating changes from baseline to the final visit using the Hamilton Depression Rating Scale-17 items (HAMD-17). This scale is a widely recognized tool for measuring depression severity and will provide quantitative data on symptom improvement.

Secondary endpoints will include the assessment of depression symptoms using the Geriatric Depression Scale-15 items (GDS-15) and the Clinical Global Impression-severity (CGI-s) scale. Additionally, cognitive symptoms associated with subthreshold depression will be evaluated using the Montreal Cognitive Assessment (MOCA) scale. These assessments will also compare baseline scores to those at the final visit, allowing for a comprehensive evaluation of both mood and cognitive changes over the course of the trial.