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Citalopram Titration in Early Non-responder Patients With Major Depressive Disorders (CRY-MOOD)

Primary Purpose

Major Depressive Disorder

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Citalopram 20mg or 40 mg (phase 2)
Sponsored by
Ciusss de L'Est de l'Île de Montréal
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring citalopram, major depressive disorder, non responder, MADRS

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Understand french or english
  • Primary diagnostic of major depressive disorder based on the Diagnostic and Statistical Manual of Mental Disorders criteria (5th edition)
  • Prescription of citalopram
  • Citalopram started less than 4 days ago
  • Able to receive informed consent
  • Not participating to another study

Exclusion Criteria:

  • Pregnancy or breastfeeding
  • Unable to participate to follow-up
  • Hypersensitivity to citalopram or any component of the formulation
  • Known QT interval prolongation or congenital long QT syndrome
  • Hepatic impairment (Child Pugh A, B or C)
  • Renal impairment (Clcr < 30 ml/min)
  • Known cytochrome P450 2C19 poor metabolizers
  • History of non-response to citalopram
  • Head trauma or severe cognitive impairment
  • Substance-related and addictive disorders controlled less than 3 months or uncontrolled
  • Schizophrenia or psychotic disorder
  • Mixed depression
  • History of manic/hypomanic episodes
  • Use of prohibited drugs : monoamine oxidase inhibitors, cytochrome P450 2C19 inhibitors, drugs at risk of causing prolongation of the QT interval, cimetidine, pimozide and antidepressors taken for another psychiatric condition.

Sites / Locations

  • GMF-U Maisonneuve-Rosemont hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

No Intervention

Arm Label

Citalopram increase (group A)

Placebo (group B)

Observational arm (group c)

Arm Description

At the end of the preparation phase, non-responders will be randomized to receive a pill of citalopram 20 mg and a capsule of citalopram 20 mg for a length of 14 days. The total dose of citalopram will be 40 mg once daily. Follow up will last 8 weeks in total.

At the end of the preparation phase, non-responders will be randomized to receive a pill of citalopram 20 mg and a capsule of placebo (a capsule without medication) for a length of 14 days. The total dose of citalopram will be 20 mg once daily. Follow up will last 8 weeks in total.

Eligible patients to this arm are responders to citalopram. A diminution of at least 30% of the symptoms from baseline with the MADRS is required to enter this arm. At the end of the first phase, these patients will pursue their citalopram 20 mg for the rest of the study (=6 weeks). It's possible that in this group, the treatment approach may vary depending the physician. Follow up will last 8 weeks in total.

Outcomes

Primary Outcome Measures

Primary outcomes determined by the proportion of non-responders (< 30 % improvement on the MADRS) after 2 weeks of treatment and the proportion of non-responders randomized patients who completed the study.
The efficacy of treatment was assessed by the Montgomery and Asberg Depression Rating Scale (MADRS).Threshold for non-responders : < 30 % improvement on the MADRS between T2 and T0. This scale was completed by a trained assessor and measures the severity of depressive episodes in patients with mood disorders. The scale is in french and has 10 items, with an overall score ranging from 0 to 60 points. Higher score indicates more severe depression. Criteria for success of the randomization and completion of the study : Sample size target : 24 non-responders randomized patients Proportion of non-responders after 2 weeks of treatment (T2) : ≥ 0.45 (number of non-responders after 2 weeks of treatment divided by the number of enrolled patients). Proportion of non-responders randomized patients who completed the full course of treatment (8 weeks) : ≥ 0.65 (number of non-responders randomized patients who completed the study divided by the total number of enrolled patients).

Secondary Outcome Measures

Proportion of eligible subjects
Number of subjects who meet the eligibility criteria divided by the total number of patients referred to the study team.
Recruitment rate
Number of enrolled patients divided by total number of patients who meet the eligibility criteria.
Retention rate
Total number of patients who completed the full course of study divided by the number of enrolled patients. A descriptive analyse will be performed to identify the reasons of prematures departures.
Adherence rate to treatment
Assessed with pill count reported to the research pharmacy at each follow-up in clinic (T2, T4, T6 and T8).
Unblinding rate
Number of unblinded patients divided by the total number of enrolled patients. A descriptive analyse will be performed to identify the reasons of unblinding.
Length of interviews
An average of all the interviews will be calculated (in minutes).
Side effects reported to the assessors and measured by the Frequency, Intensity, and Burden of Side Effect Rating (FIBSER).
The side effects were reported to assessor and their gravity were measured by a self-administrated scale called the FIBSER.The FIBSER is composed of 3 questions and takes 3 distinct aspects : frequency, intensity and the burden of side effect on the quality of life. The scale was in french and has 3 questions, with an overall score ranging from 0 to 18 points. Higher score indicates a high side-effect burden that should be evaluated.
Response curves for all patients according to the results from the MADRS.
Compare the clinical response following the increase of citalopram at 2 weeks (group A) or 4 weeks (group B) in non-responder patients according to the results from the Montgomery and Asberg Depression Rating Scale (MADRS) at T2, T4, T6 and T8. This scale was completed by a trained assessor and measures the severity of depressive episodes in patients with mood disorders. The scale is in french and has 10 items, with an overall score ranging from 0 to 60 points. Higher score indicates more severe depression.
Correlation between the results of Patient Health Questionnaire-9 (PHQ-9) and the MADRS at each follow-up (T2, T4, T6 and T8).
A pearson coefficient to describe the correlation (r) between the PHQ-9 and the Montgomery and Asberg Depression Rating Scale (MADRS) was chosen. The PHQ-9 is a questionnaire self-reported assessing the severity of the depression. The scale was in french and has 9 items, with an overall score ranging from 0 to 27 points. Higher score indicates more severe depression. The MADRS was completed by a trained assessor and measures the severity of depressive episodes in patients with mood disorders. The scale is in french and has 10 items, with an overall score ranging from 0 to 60 points. Higher score indicates more severe depression.

Full Information

First Posted
August 24, 2018
Last Updated
April 2, 2019
Sponsor
Ciusss de L'Est de l'Île de Montréal
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1. Study Identification

Unique Protocol Identification Number
NCT03899285
Brief Title
Citalopram Titration in Early Non-responder Patients With Major Depressive Disorders
Acronym
CRY-MOOD
Official Title
Citalopram Titration in Early Non-responder Patients With Major Depressive Disorders: a Pilot Study (CRY-MOOD)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
January 8, 2018 (Actual)
Primary Completion Date
December 8, 2018 (Actual)
Study Completion Date
December 8, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ciusss de L'Est de l'Île de Montréal

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
Major depressive disorder is a common mental disorder and the leading cause of disability worldwide. According to the Canadian Network for Mood and Anxiety Treatment, early improvement following an antidepressant treatment is correlated with response and remission. Escalation of an antidepressant dose after 2 weeks, as opposed to 4 to 8 weeks, is proposed to favor early improvement. However, this has never been tested systematically in a controlled study involving major depressive disorder patients that are non-responders to their antidepressant treatment.
Detailed Description
The investigators sought to assess whether it is feasible to perform a prospective randomized controlled double-blind feasibility study with a 2 week run-in period and 3 parallel groups randomized controlled study using citalopram. Citalopram has physicochemical properties compatible with over-encapsulation and a has a simple titration that allows the study of early dose increase.. It is among the most prescribed antidepressant in the province of Quebec and at the Hospital Maisonneuve-Rosemont - University family medicine group (U-FMG). Since establishment of a randomized controlled trial is complex and expensive, a feasibility design is appropriate to identify all the obstacles and to minimize sources of possible bias (recruitment, follow up, resources).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder
Keywords
citalopram, major depressive disorder, non responder, MADRS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Preparation phase (Phase 1) : Every enrolled patients start with citalopram 10 mg daily for 3 days and 20 mg daily for 11 days. Escalation phase (Phase 2) :This phase is split in two arms which are the responders and the non-responders. Responders will pursue their citalopram 20 mg for 14 days. Non-responders will be assigned randomly 1:1 in 2 groups. Patients in group A will be randomized to receive a pill of citalopram 20 mg and a capsule of citalopram 20 mg for 14 days. The total dose of citalopram will be 40 mg once daily. Patients in group B receive a pill of citalopram 20 mg and a capsule of placebo (a capsule without medication) for 14 days. The total dose of citalopram will be 20 mg once daily. Follow-up phase (Phase 3) : Every responders will pursue their treatment of citalopram 20 mg daily for 28 days. It's possible that in this group, the treatment approach may vary depending the physician. Every non-responders (group A and B) will receive 40 mg of citalopram for 28 days.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Over-encapsulation was performed to maintain blind. Every participant will have the same step (visits, follow up, questionnaire and interview).
Allocation
Randomized
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Citalopram increase (group A)
Arm Type
Experimental
Arm Description
At the end of the preparation phase, non-responders will be randomized to receive a pill of citalopram 20 mg and a capsule of citalopram 20 mg for a length of 14 days. The total dose of citalopram will be 40 mg once daily. Follow up will last 8 weeks in total.
Arm Title
Placebo (group B)
Arm Type
Placebo Comparator
Arm Description
At the end of the preparation phase, non-responders will be randomized to receive a pill of citalopram 20 mg and a capsule of placebo (a capsule without medication) for a length of 14 days. The total dose of citalopram will be 20 mg once daily. Follow up will last 8 weeks in total.
Arm Title
Observational arm (group c)
Arm Type
No Intervention
Arm Description
Eligible patients to this arm are responders to citalopram. A diminution of at least 30% of the symptoms from baseline with the MADRS is required to enter this arm. At the end of the first phase, these patients will pursue their citalopram 20 mg for the rest of the study (=6 weeks). It's possible that in this group, the treatment approach may vary depending the physician. Follow up will last 8 weeks in total.
Intervention Type
Drug
Intervention Name(s)
Citalopram 20mg or 40 mg (phase 2)
Intervention Description
For non-responders, a randomisation 1:1 was chosen. The group A will receive 40 mg and the group B will receive 20 mg once daily of citalopram for 14 days.
Primary Outcome Measure Information:
Title
Primary outcomes determined by the proportion of non-responders (< 30 % improvement on the MADRS) after 2 weeks of treatment and the proportion of non-responders randomized patients who completed the study.
Description
The efficacy of treatment was assessed by the Montgomery and Asberg Depression Rating Scale (MADRS).Threshold for non-responders : < 30 % improvement on the MADRS between T2 and T0. This scale was completed by a trained assessor and measures the severity of depressive episodes in patients with mood disorders. The scale is in french and has 10 items, with an overall score ranging from 0 to 60 points. Higher score indicates more severe depression. Criteria for success of the randomization and completion of the study : Sample size target : 24 non-responders randomized patients Proportion of non-responders after 2 weeks of treatment (T2) : ≥ 0.45 (number of non-responders after 2 weeks of treatment divided by the number of enrolled patients). Proportion of non-responders randomized patients who completed the full course of treatment (8 weeks) : ≥ 0.65 (number of non-responders randomized patients who completed the study divided by the total number of enrolled patients).
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Proportion of eligible subjects
Description
Number of subjects who meet the eligibility criteria divided by the total number of patients referred to the study team.
Time Frame
8 weeks
Title
Recruitment rate
Description
Number of enrolled patients divided by total number of patients who meet the eligibility criteria.
Time Frame
8 weeks
Title
Retention rate
Description
Total number of patients who completed the full course of study divided by the number of enrolled patients. A descriptive analyse will be performed to identify the reasons of prematures departures.
Time Frame
8 weeks
Title
Adherence rate to treatment
Description
Assessed with pill count reported to the research pharmacy at each follow-up in clinic (T2, T4, T6 and T8).
Time Frame
8 weeks
Title
Unblinding rate
Description
Number of unblinded patients divided by the total number of enrolled patients. A descriptive analyse will be performed to identify the reasons of unblinding.
Time Frame
8 weeks
Title
Length of interviews
Description
An average of all the interviews will be calculated (in minutes).
Time Frame
8 weeks
Title
Side effects reported to the assessors and measured by the Frequency, Intensity, and Burden of Side Effect Rating (FIBSER).
Description
The side effects were reported to assessor and their gravity were measured by a self-administrated scale called the FIBSER.The FIBSER is composed of 3 questions and takes 3 distinct aspects : frequency, intensity and the burden of side effect on the quality of life. The scale was in french and has 3 questions, with an overall score ranging from 0 to 18 points. Higher score indicates a high side-effect burden that should be evaluated.
Time Frame
8 weeks
Title
Response curves for all patients according to the results from the MADRS.
Description
Compare the clinical response following the increase of citalopram at 2 weeks (group A) or 4 weeks (group B) in non-responder patients according to the results from the Montgomery and Asberg Depression Rating Scale (MADRS) at T2, T4, T6 and T8. This scale was completed by a trained assessor and measures the severity of depressive episodes in patients with mood disorders. The scale is in french and has 10 items, with an overall score ranging from 0 to 60 points. Higher score indicates more severe depression.
Time Frame
8 weeks
Title
Correlation between the results of Patient Health Questionnaire-9 (PHQ-9) and the MADRS at each follow-up (T2, T4, T6 and T8).
Description
A pearson coefficient to describe the correlation (r) between the PHQ-9 and the Montgomery and Asberg Depression Rating Scale (MADRS) was chosen. The PHQ-9 is a questionnaire self-reported assessing the severity of the depression. The scale was in french and has 9 items, with an overall score ranging from 0 to 27 points. Higher score indicates more severe depression. The MADRS was completed by a trained assessor and measures the severity of depressive episodes in patients with mood disorders. The scale is in french and has 10 items, with an overall score ranging from 0 to 60 points. Higher score indicates more severe depression.
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Understand french or english Primary diagnostic of major depressive disorder based on the Diagnostic and Statistical Manual of Mental Disorders criteria (5th edition) Prescription of citalopram Citalopram started less than 4 days ago Able to receive informed consent Not participating to another study Exclusion Criteria: Pregnancy or breastfeeding Unable to participate to follow-up Hypersensitivity to citalopram or any component of the formulation Known QT interval prolongation or congenital long QT syndrome Hepatic impairment (Child Pugh A, B or C) Renal impairment (Clcr < 30 ml/min) Known cytochrome P450 2C19 poor metabolizers History of non-response to citalopram Head trauma or severe cognitive impairment Substance-related and addictive disorders controlled less than 3 months or uncontrolled Schizophrenia or psychotic disorder Mixed depression History of manic/hypomanic episodes Use of prohibited drugs : monoamine oxidase inhibitors, cytochrome P450 2C19 inhibitors, drugs at risk of causing prolongation of the QT interval, cimetidine, pimozide and antidepressors taken for another psychiatric condition.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marie-Claude Lefebvre, MD
Organizational Affiliation
GMF-U Maisonneuve-Rosemont Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
GMF-U Maisonneuve-Rosemont hospital
City
Montréal-Est
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada

12. IPD Sharing Statement

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Citalopram Titration in Early Non-responder Patients With Major Depressive Disorders

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