Major Depressive DisorderPhase 2CRY-MOODNCT03899285
Citalopram Titration in Early Non-responder Patients With Major Depressive Disorders
A Phase 2 study testing Citalopram 20mg or 40 mg (phase 2) in people with Major Depressive Disorder, run by Ciusss de L'Est de l'Île de Montréal at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Citalopram 20mg or 40 mg (phase 2)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteCanada
- Study dates
- 8 Jan 2018to 8 Dec 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country.
Canada1 site
GMF-U Maisonneuve-Rosemont hospital
Montreal East, Quebec, H1T 2M4
About this study
Official title: Citalopram Titration in Early Non-responder Patients With Major Depressive Disorders: a Pilot Study (CRY-MOOD)
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.
Read the 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).
- Conditions
- Major Depressive Disorder
- Being tested
- Citalopram 20mg or 40 mg (phase 2)
- Keywords
- citalopram, major depressive disorder, non responder, MADRS
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Citalopram 20mg or 40 mg (phase 2)Drug
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 group | Role | What they receive |
|---|---|---|
| Citalopram increase (group A) | Experimental | 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. Receives: Drug: Citalopram 20mg or 40 mg (phase 2) |
| Placebo (group B) | Placebo comparator | 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. Receives: Drug: Citalopram 20mg or 40 mg (phase 2) |
| Observational arm (group c) | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 8 weeks
Secondary outcomes (9)
Proportion of eligible subjects
Number of subjects who meet the eligibility criteria divided by the total number of patients referred to the study team.
Measured: 8 weeks
Recruitment rate
Number of enrolled patients divided by total number of patients who meet the eligibility criteria.
Measured: 8 weeks
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.
Measured: 8 weeks
Adherence rate to treatment
Assessed with pill count reported to the research pharmacy at each follow-up in clinic (T2, T4, T6 and T8).
Measured: 8 weeks
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.
Measured: 8 weeks
Length of interviews
An average of all the interviews will be calculated (in minutes).
Measured: 8 weeks
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.
Measured: 8 weeks
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.
Measured: 8 weeks
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.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2019
- Study start8 Jan 2018
- Primary completion8 Dec 2018
- Study completion8 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ciusss de L'Est de l'Île de Montréal
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marie-Claude Lefebvre, Ciusss de L'Est de l'Île de Montréal
- Investigators
- Marie-Claude Lefebvre, MD, Principal investigator, GMF-U Maisonneuve-Rosemont Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03899285
- Sponsor's protocol ID
- 2018-1215
- Acronym
- CRY-MOOD
- Status last verified
- Apr 2019
- First submitted
- 24 Aug 2018
- Last updated
- 4 Apr 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Citalopram Titration in Early Non-responder Patients With Major Depressive Disorders: a Pilot Study (CRY-MOOD)
- ClinicalTrials.gov ID
- NCT03899285
- Acronym / sponsor ID
- CRY-MOOD / 2018-1215
- Conditions
- Major Depressive Disorder
- Keywords
- citalopram, major depressive disorder, non responder, MADRS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Ciusss de L'Est de l'Île de MontréalUniversity, hospital or other
- Study start
- 8 Jan 2018 (actual)
- Primary completion
- 8 Dec 2018 (actual)
- Study completion
- 8 Dec 2018 (actual)
- First posted
- 2 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- 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.
| Arm | Type | Receives |
|---|---|---|
| Citalopram increase (group A) | Experimental | Drug: Citalopram 20mg or 40 mg (phase 2)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. |
| Placebo (group B) | Placebo comparator | Drug: Citalopram 20mg or 40 mg (phase 2)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. |
| Observational arm (group c) | No intervention | –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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (14 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Citalopram increase (group A), Placebo (group B) |
Primary outcome
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).
9 secondary outcomes
Proportion of eligible subjects
Time frame: 8 weeks
Recruitment rate
Time frame: 8 weeks
Retention rate
Time frame: 8 weeks
Adherence rate to treatment
Time frame: 8 weeks
Unblinding rate
Time frame: 8 weeks
Length of interviews
Time frame: 8 weeks
Side effects reported to the assessors and measured by the Frequency, Intensity, and Burden of Side Effect Rating (FIBSER).
Time frame: 8 weeks
Response curves for all patients according to the results from the MADRS.
Time frame: 8 weeks
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marie-Claude Lefebvre, MD principal investigator
GMF-U Maisonneuve-Rosemont Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Citalopram 20mg or 40 mg (phase 2) in people with Major Depressive Disorder, run by Ciusss de L'Est de l'Île de Montréal at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2019.