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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03899285
Recruitment Status : Completed
First Posted : April 2, 2019
Last Update Posted : April 4, 2019
Sponsor:
Information provided by (Responsible Party):
Marie-Claude Lefebvre, Ciusss de L'Est de l'Île de Montréal

Tracking Information
First Submitted Date  ICMJE August 24, 2018
First Posted Date  ICMJE April 2, 2019
Last Update Posted Date April 4, 2019
Actual Study Start Date  ICMJE January 8, 2018
Actual Primary Completion Date December 8, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 29, 2019)
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. [ Time Frame: 8 weeks ]
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2019)
  • Proportion of eligible subjects [ Time Frame: 8 weeks ]
    Number of subjects who meet the eligibility criteria divided by the total number of patients referred to the study team.
  • Recruitment rate [ Time Frame: 8 weeks ]
    Number of enrolled patients divided by total number of patients who meet the eligibility criteria.
  • Retention rate [ Time Frame: 8 weeks ]
    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 [ Time Frame: 8 weeks ]
    Assessed with pill count reported to the research pharmacy at each follow-up in clinic (T2, T4, T6 and T8).
  • Unblinding rate [ Time Frame: 8 weeks ]
    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 [ Time Frame: 8 weeks ]
    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). [ Time Frame: 8 weeks ]
    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. [ Time Frame: 8 weeks ]
    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). [ Time Frame: 8 weeks ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2019)
  • Proportion of eligible subjects [ Time Frame: 8 weeks ]
    Number of subjects who meet the eligibility criteria divided by the total number of patients referred to the study team.
  • Recruitment rate [ Time Frame: 8 weeks ]
    Number of enrolled patients divided by total number of patients who meet the eligibility criteria.
  • Retention rate [ Time Frame: 8 weeks ]
    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 [ Time Frame: 8 weeks ]
    Assessed with pill count reported to the research pharmacy at each follow-up in clinic (T2, T4, T6 and T8).
  • Unblinding rate [ Time Frame: 8 weeks ]
    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 [ Time Frame: 8 weeks ]
    An average of all the interviews will be calculated (in minutes).
  • Side effects reported to the assessors and measured by the FIBSER. [ Time Frame: 8 weeks ]
    The side effects were reported to assessor and their gravity were measured by a self-administrated scale called The Frequency, Intensity, and Burden of Side Effect Rating (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. [ Time Frame: 8 weeks ]
    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 MADRS at T2, T4, T6 and T8.
  • Correlation between the results of Patient Health Questionnaire-9 (PHQ-9) and the MADRS at each follow-up (T2, T4, T6 and T8). [ Time Frame: 8 weeks ]
    A pearson coefficient to describe the correlation (r) between the PHQ-9 and the 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Citalopram Titration in Early Non-responder Patients With Major Depressive Disorders
Official Title  ICMJE Citalopram Titration in Early Non-responder Patients With Major Depressive Disorders: a Pilot Study (CRY-MOOD)
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Over-encapsulation was performed to maintain blind.

Every participant will have the same step (visits, follow up, questionnaire and interview).

Primary Purpose: Treatment
Condition  ICMJE Major Depressive Disorder
Intervention  ICMJE Drug: Citalopram 20mg or 40 mg (phase 2)
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.
Study Arms  ICMJE
  • Experimental: Citalopram increase (group A)

    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.

    Intervention: Drug: Citalopram 20mg or 40 mg (phase 2)
  • Placebo Comparator: Placebo (group B)

    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.

    Intervention: Drug: Citalopram 20mg or 40 mg (phase 2)
  • No Intervention: Observational arm (group c)

    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.

Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 29, 2019)
8
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 8, 2018
Actual Primary Completion Date December 8, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03899285
Other Study ID Numbers  ICMJE 2018-1215
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Marie-Claude Lefebvre, Ciusss de L'Est de l'Île de Montréal
Study Sponsor  ICMJE Ciusss de L'Est de l'Île de Montréal
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Marie-Claude Lefebvre, MD GMF-U Maisonneuve-Rosemont Hospital
PRS Account Ciusss de L'Est de l'Île de Montréal
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP