Safety of Liposom With Citalopram in Elderly Patients With Major Depressive Disorder

Phase 4

Recruiting

• Conditions: Major Depressive Disorder
• Interventions: Drug: Liposom Forte; Drug: Citalopram; Other: Placebo

• Registration Number: NCT04975724
• Lead Sponsor: Fidia Farmaceutici s.p.a.

Brief Summary

The purpose of this study is to determine if Liposom Forte will enhance the response to antidepressant therapy with citalopram in elderly patients suffering from Major Depressive Disorder (MDD).

Detailed Description

The effects of phospholipid liposomes when associated with antidepressant drugs are very interesting. In addition to an improvement of somatic symptoms of depression, measured with the Hamilton Rate Scale for Depression, liposomes are able to reduce the latency of onset of the antidepressant activity of drugs like amitriptyline, clomipramine, and trazodone. These results indicate that phospholipids can be used as an adjuvant to antidepressant therapy, also allowing specific antidepressant drug dose reduction. Thus, the hypothesis is that combination therapy would not only lead to greater efficacy, but also to a more rapid onset of therapeutic response. The addition of Liposom Forte may be clinically important since it may ensure the use of lower citalopram doses, thereby reducing the risk of adverse events, and this may prove to be important, especially in elderly people.

Study Timeline

• Study Start: 2019-04-18
• Study First Submitted: 2020-03-02
• Study First Submitted QC: 2021-07-14
• Study First Posted: 2021-07-23
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-12
• Last Update Posted: 2024-01-17
• Primary Completion: 2025-10
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1. Meets DSM-V criteria for major depressive disorder
2. Score of ≥ 16 in the HAM-D
3. Score of ≥ 23 on the Mini-Mental State Exam (MMSE-2)
4. Aged ≥ 65 and < 85 years
5. Patients able to understand the study procedures and to comply with protocol requirements
6. Patients legally able to give written informed consent to the trial (signed and dated by the subject)

Exclusion Criteria

1. Any contraindication for treatment or intolerance to Liposom Forte or citalopram
2. Congenital long QT syndrome, bradycardia, recent acute myocardial infarction, uncompensated heart failure or concomitant use of drugs that prolong the QT interval
3. History of psychiatric disorder other than major depressive disorder, including history of substance use disorder
4. Presence of psychotic symptoms, even if they are not sufficient to make diagnosis of a mental disorder
5. Severe organic disease (e.g., major surgery, metastatic cancer, stroke, delirium, severe neurological disorder, heart attack, chronic heart failure, asthma, severe cardio circulatory disorders)
6. Diabetes Mellitus type I and II
7. Acute suicidal or violent behaviour or history of suicide attempt within the year prior to study entry or current suicidal ideation
8. Treated with long acting injectable (LAI) antipsychotics within 6 months prior to study entry
9. Treated with any antipsychotics, antidepressant, food supplements or over-the-counter CNS-active medications (e.g, St. John's Wort, melatonin, Selective Serotonin Reuptake Inhibitors [SSRIs], Serotonin and norepinephrine reuptake inhibitors [SNRIs], Monoamine-Oxidase Inhibitors [MAOIs], or other antidepressants) within 4 weeks prior to the first administration of study medication
10. Ongoing or planned psychotherapy or other psychological treatment during the study period

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A Liposom Forte + Citalopram	Liposom Forte	Liposom Forte (2 ampoules of 28mg/2 ml) for 30 days + citalopram (10mg) for 90 days
Group B Placebo + Citalopram	Citalopram	Placebo (2 ampoules of 2 ml) for 30 days + citalopram (10mg) for 90 days
Group B Placebo + Citalopram	Placebo	Placebo (2 ampoules of 2 ml) for 30 days + citalopram (10mg) for 90 days
Group A Liposom Forte + Citalopram	Citalopram	Liposom Forte (2 ampoules of 28mg/2 ml) for 30 days + citalopram (10mg) for 90 days

Primary Outcome Measures

Name	Time	Method
Change of depressive symptoms atV5(day30)as change from baseline with HamiltonRatingScaleforDepression (21items,scoring based on the first17.9items from0=not present;to4=severe.8 from0-2.Scores from the first17items summed:≥16=MajorDep)	Day 30 (V5)	The purpose of this study is to determine if Liposom Forte will enhance the response to antidepressant therapy with citalopram in elderly patients suffering from Major Depressive Disorder (MDD). HamiltonRatingScaleforDepression (21items,scoring based on the first17.9items from0=not present;to4=severe.8 from0-2.Scores from the first17items summed:≥16=MajorDep)

Secondary Outcome Measures

Name	Time	Method
Change of latency of antidepressant therapy with citalopram. Evaluated at V2,V3,V4 and V5 using HamiltonRatingScaleforDepression Latency time:the time from baseline to response (a≥50% improvement in HAM-D score vs baseline)	From baseline through 30 days follow-up (V5)	Determine if Liposom Forte will speed up response to antidepressant therapy with citalopram HamiltonRatingScaleforDepression (21items,scoring based on the first17.9items from0=not present;to4=severe.8 from0-2.Scores from the first17items summed:≥16=MajorDep)
Percentage of patients responders at V2, V3, V4 and V5. ≥50% improvement in HAM-D score vs baseline will be considered as responder.	From baseline through 30 days follow-up (V5)	determine if Liposom Forte will speed up response to antidepressant therapy with citalopram
Change of depressive symptoms as change from baseline using Geriatric Depression Scale (GDS-15).	From baseline through 90 days follow-up (V8)	Change of depressive symptoms will be evaluated over the entire study. GDS:brief questionnaire:15questions with options yes or no in reference to how patients felt on the day of administration. Answers indicating depression are in bold and italicized; score one point for each one selected. A score of 0 to 5 is normal. A score greater than 5 suggests depression.
ClinicalGlobalImpression as change from baseline up toV8Day90.CGI:7point scale clinician-rated(severity of illness)from1(normal)to7(severely ill).CGI score from1(very much improved)to7(very much worse).Treatment response consider efficacy andAEs	From baseline through 90 days follow-up (V8)	Determine the Clinical Global Impression to treatments
Safety of study treatments by tracking number and type of adverse events at each visit, up to V8 (Day 90)	From baseline through 90 days follow-up (V8)	To assess the safety of study treatments
Safety of study treatments by tracking, up to V8 (Day 90), blood pressure measurements in mmHg	From baseline through 90 days follow-up (V8)	To assess the safety of study treatments tracking blood pressure measurement in mmHg
Safety of study treatments by tracking, up to V8 (Day 90), 12-lead ECG, QTcF interval (Fridericia equation) will be measured	From baseline to Day 14 (V3) and Day 90 (V8)	To assess the safety of study treatments
Change of depressive symptoms during the entire study as change from baseline therapy with citalopram over the entire study	From baseline through 90 days follow-up (V8)	Change of depressive symptoms will be evaluated over the entire study as change from baseline using the HAM-D (Hamilton Rating Scale for Depression). The score is based on the first 17 items: nine items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Eight are scored from 0-2. The score is summed and patients are categorized as follows: 0-7 = No depression 8-15 = Minor Depression; ≥ 16 = Major Depression
Safety of study treatments by tracking, up to V8 (Day 90), heart rate measurements in bpm	From baseline through 90 days follow-up (V8)	To assess the safety of study treatments tracking heart rate
Safety of study treatments by tracking, up to V8 (Day 90), oxygen saturation measurements in percentage with a pulse oximetry device	From baseline through 90 days follow-up (V8)	To assess the safety of study treatments tracking oxygen saturation

Trial Locations

Locations (12)

SOD Geriatria-UTIG Azienda Ospedaliero-Universitaria Careggi; 🇮🇹 Firenze, Italy

Clinica Psichiatrica, Azienda Sanitaria Universitaria Integrata di Udine; 🇮🇹 Udine, Italy

UOC Geriatria e Lungodegenza Geriatrica PO San Filippo e Nicola di Avezzano - ASL1 Avezzano Sulmona L'aquila; 🇮🇹 Avezzano, Italy

UO Psichiatria - ASST Papa Giovanni XXIII; 🇮🇹 Bergamo, Italy

Ambulatorio Psichiatrico, UOC Psichiatria Presidio Ospedaliero di Codogno - ASST Lodi; 🇮🇹 Codogno, Italy

Servizio Psichiatrico di Diagnosi e Cura (SPDC) Foggia, Ospedali Riuniti di Foggia; 🇮🇹 Foggia, Italy

Servizio Psichiatrico di Diagnosi e Cura (SPDC) - ASL3 Ente Ospedaliero Ospedali Galliera; 🇮🇹 Genova, Italy

Ambulatorio Clinica Psichiatrica, Ospedale Policlinico S. Martino; 🇮🇹 Genova, Italy

UOC Geriatria PO San Salvatore - ASL1 Avezzano Sulmona L'Aquila; 🇮🇹 L'Aquila, Italy

SPDC Ospedale Fatebenefratell, UOC Psichiatria 1 ASST Fatebenefratelli Sacco; 🇮🇹 Milano, Italy

UOC Psichiatria - Azienda Ospedaliero-Universitaria Sant'Andrea; 🇮🇹 Roma, Italy

Centro Depressione Anziani S.C. Psichiatria 51, ASST Santi Paolo e Carlo - Presidio San Paolo; 🇮🇹 Milano, Italy