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

A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Trial to Assess Safety and Effectiveness of Liposom in Enhance and Speed up Response With Citalopram in Elderly Patients Suffering From Major Depressive Disorder (MDD)

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).

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Liposom Forte; Drug: Citalopram; Other: Placebo

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 Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Nicola Giordan, Dr; Phone Number: 0039 049 8232512; Email: ngiordan@fidiapharma.it

Study Locations

• Italy
  • Avezzano, Italy, 67051
    • Recruiting
    • UOC Geriatria e Lungodegenza Geriatrica PO San Filippo e Nicola di Avezzano - ASL1 Avezzano Sulmona L'aquila
    • Contact: Giovambattista Desideri
  • Bergamo, Italy, 24127
    • Active, not recruiting
    • UO Psichiatria - ASST Papa Giovanni XXIII
  • Codogno, Italy, 26845
    • Active, not recruiting
    • Ambulatorio Psichiatrico, UOC Psichiatria Presidio Ospedaliero di Codogno - ASST Lodi
  • Firenze, Italy, 50100
    • Active, not recruiting
    • SOD Geriatria-UTIG Azienda Ospedaliero-Universitaria Careggi
  • Foggia, Italy, 71122
    • Active, not recruiting
    • Servizio Psichiatrico di Diagnosi e Cura (SPDC) Foggia, Ospedali Riuniti di Foggia
  • Genova, Italy, 16128
    • Active, not recruiting
    • Servizio Psichiatrico di Diagnosi e Cura (SPDC) - ASL3 Ente Ospedaliero Ospedali Galliera
  • Genova, Italy, 16132
    • Active, not recruiting
    • Ambulatorio Clinica Psichiatrica, Ospedale Policlinico S. Martino
  • L'Aquila, Italy, 67100
    • Active, not recruiting
    • UOC Geriatria PO San Salvatore - ASL1 Avezzano Sulmona L'Aquila
  • Milano, Italy, 20121
    • Recruiting
    • SPDC Ospedale Fatebenefratell, UOC Psichiatria 1 ASST Fatebenefratelli Sacco
    • Contact: Bernardo Dell'Osso
  • Milano, Italy, 20142
    • Recruiting
    • Centro Depressione Anziani S.C. Psichiatria 51, ASST Santi Paolo e Carlo - Presidio San Paolo
    • Contact: Simone Cavallotti
  • Roma, Italy, 00189
    • Active, not recruiting
    • UOC Psichiatria - Azienda Ospedaliero-Universitaria Sant'Andrea
  • Udine, Italy, 33100
    • Recruiting
    • Clinica Psichiatrica, Azienda Sanitaria Universitaria Integrata di Udine
    • Contact: Matteo Balestrieri

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 84 years (Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A Liposom Forte + Citalopram; Liposom Forte (2 ampoules of 28mg/2 ml) for 30 days + citalopram (10mg) for 90 days	Drug: Liposom Forte; Liposom Forte 28mg/2ml solution for injection contains a mixture of purified hypothalamic phospholipids (PLs) from swine brains. The key components of the phospholipid mixture are phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS).; Other Names: Liposom; Drug: Citalopram; The medicinal product Citalopram Aurobindo contains citalopram as active ingredient available on the market in 20 mg film coated tablets. The tablets are divisible in two equal part of 10 mg as reported in the SmPC
Experimental: Group B Placebo + Citalopram; Placebo (2 ampoules of 2 ml) for 30 days + citalopram (10mg) for 90 days	Drug: Citalopram; The medicinal product Citalopram Aurobindo contains citalopram as active ingredient available on the market in 20 mg film coated tablets. The tablets are divisible in two equal part of 10 mg as reported in the SmPC; Other: Placebo; Liposom Forte Placebo (2 ampoules of 2 ml solution for injection); Other Names: Placebo of Liposom Forte

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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)	Day 30 (V5)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of study treatments by tracking number and type of adverse events at each visit, up to V8 (Day 90)	To assess the safety of study treatments	From baseline through 90 days follow-up (V8)
Safety of study treatments by tracking, up to V8 (Day 90), 12-lead ECG, QTcF interval (Fridericia equation) will be measured	To assess the safety of study treatments	From baseline to Day 14 (V3) and Day 90 (V8)
Safety of study treatments by tracking, up to V8 (Day 90), blood pressure measurements in mmHg	To assess the safety of study treatments tracking blood pressure measurement in mmHg	From baseline through 90 days follow-up (V8)
Safety of study treatments by tracking, up to V8 (Day 90), heart rate measurements in bpm	To assess the safety of study treatments tracking heart rate	From baseline through 90 days follow-up (V8)
Safety of study treatments by tracking, up to V8 (Day 90), oxygen saturation measurements in percentage with a pulse oximetry device	To assess the safety of study treatments tracking oxygen saturation	From baseline through 90 days follow-up (V8)
Change of depressive symptoms during the entire study as change from baseline therapy with citalopram over the entire study	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	From baseline through 90 days follow-up (V8)
Percentage of patients responders at V2, V3, V4 and V5. ≥50% improvement in HAM-D score vs baseline will be considered as responder.	determine if Liposom Forte will speed up response to antidepressant therapy with citalopram	From baseline through 30 days follow-up (V5)
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)	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)	From baseline through 30 days follow-up (V5)
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	Determine the Clinical Global Impression to treatments	From baseline through 90 days follow-up (V8)
Change of depressive symptoms as change from baseline using Geriatric Depression Scale (GDS-15).	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.	From baseline through 90 days follow-up (V8)

Collaborators and Investigators

• Sponsor: Fidia Farmaceutici s.p.a.
• Investigators: Study Director: Nicola Giordan, Fidia Farmaceutici s.p.a.

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2019
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 2, 2020
• First Submitted That Met QC Criteria: July 14, 2021
• First Posted (Actual): July 23, 2021

Study Record Updates

• Last Update Posted (Actual): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Selective Serotonin Reuptake Inhibitors; Citalopram
• Other Study ID Numbers: QQ05.16.02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No