search
Back to results

Lithium Versus Cariprazine in the Acute Phase Treatment of Bipolar Depression (DUAG9) (DUAG9)

Primary Purpose

Depression, Bipolar

Status
Recruiting
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Lithium
Cariprazine
Sponsored by
Aalborg University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Depression, Bipolar

Eligibility Criteria

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

Inclusion Criteria: A diagnosis of bipolar disorder, type 1 or type 2, and a current episode of depression according to DSM-5 Severity of depression: A score of at least 21 on the self-reported Major Depression Inventory (MDI). No start or dose increase of psychotropic medication (except for benzodiazepines and benzodiazepine-like drugs (zopiclone, zolpidem, and melatonin)) in the two weeks prior to inclusion. No new start of formalized psychotherapy sessions, excluding psychoeducation, during the 4 weeks prior to inclusion. Age criteria: Subjects must be at least 18 years old and below 65 at the time of randomization. The duration of the current depressive episode must be between 4 and 52 weeks as judged by the investigator at the time of randomization. Clinical uncertainty regarding which of the alternatives, cariprazine and lithium, would be the better choice in the specific case. Female participants should be sterile or non-fertile or, in case of being fertile, they must have a negative pregnancy test AND use safe anticonception. Signed document of informed consent. Exclusion Criteria: Prior or ongoing acute treatment of a depressive episode lasting > 14 days with either lithium or cariprazine as judged by the investigator. ECT within the current depressive episode. A score of MAS > 6. A diagnosis of dementia. High risk of non-adherence at the investigator's discretion. Not understanding the Danish language as judged by the investigator Psychiatric coercion in the form of forced admission or detainment OR sentence to forensic psychiatric care. Presence of clinically relevant delusions, hallucinations or other psychotic symptoms as judged by the investigator. Suicidality according to C-SSRS with a positive response to question 4 or 5 or upon investigator's discretion. Medical conditions like cancer, kidney failure, epilepsy, deep brain stimulation device, or other medical conditions interfering with study the outcome and safety as judged by investigator's discretion. Current harmful use or dependency of alcohol or drugs according to DSM-5. Known allergy to any of the substances in the study medication.

Sites / Locations

  • Aalborg University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Lithium

Cariprazine

Arm Description

Lithium citrate from 12 mmol increased to result in af 12-hour se-lithium between 0.6 and 0.8 mmol/l

Cariprazine from 1.5 mg to 3 mg daily in a single dose.

Outcomes

Primary Outcome Measures

Change in Hamilton Depressions scale, version 6 (HDS-6)
The primary aim is to investigate whether cariprazine is superior to lithium or vice versa in the acute treatment of patients with bipolar type 1 or 2 in a current depressive episode measured as change on the Hamilton Depression Scale, 6 item version, HDS-6. (Values 0- 22, higher scores mean a worse outcome).

Secondary Outcome Measures

Difference-in-difference for HDS-17
Difference-in-differences for secondary continuous measures: Hamilton Depression Scale, 17 item version, HDS-17. (Values 0- 52, higher scores mean a worse outcome)
Difference-in-differences in HDS-6 for the PP 8 population
Difference-in-differences (baseline to 8 weeks) in HDS-6 for the PP 8 population. Hamilton Depression Scale, 6 item version, HDS-6. (Values 0- 22, higher scores mean a worse outcome).
Between-groups difference in proportion of responders and remitters in HDS-6 Scores.
Between-groups difference in proportion of responders and remitters at week 4 and 8 in HDS-6 scores. Hamilton Depression Scale, 6 item version, HDS-6. (Values 0- 22, higher scores mean a worse outcome).
Between-groups difference in proportion of responders and remitters
Between-groups difference in proportion of responders and remitters with response and remission defined by HDS-6 score without clinical relevant manic symptoms (MAS <7) at planned or premature endpoint. Hamilton Depression Scale, 6 item version, HDS-6. (Values 0- 22, higher scores mean a worse outcome).
Between-groups difference in the proportion of patients with 'acceptable wellbeing'
Between-groups difference in the proportion of patients with 'acceptable wellbeing', defined as the subject reporting ≥50 on the WHO-5 questionnaire at endpoint. WHO-five Well-being Index, WHO-5 (Values 0- 100, higher scores mean a better outcome).
Between-groups difference in proportion of switches to mania/hypomania.
Between-groups difference in proportion of switches to mania/hypomania with or without mixed features, defined as mania/hypomania after DSM-5 or symptoms requiring treatment (switch or response occurring at any time in the study period)
Between-groups difference in "(switch to mania or hypomania) / (response) -ratio",
Between-groups difference in "(switch to mania or hypomania) / (response) -ratio", defined as the number of subjects switching to mania or hypomania (as defined above) divided by the total number of responders, including those responders switching to mania
Between-group differences in reason for and time to all cause treatment discontinuation
Between-group differences in reason for and time to all cause treatment discontinuation (lack of effect, lack of tolerability, lost to follow-up, or other cause).
Between-group difference in treatment compliance.
Between-group difference in treatment compliance. Treatment compliance is defined as the proportion of received treatments out of the planned until drop-out or end of study.
Between-group difference in reasons for premature discontinuation
Between-group difference for the ITT population in reasons for premature discontinuation
Difference-in-difference for MAS
Difference-in-differences for secondary continuous measures: MAS Bech-Rafaelsens Mania scale .(Values 0- 44, higher scores mean a worse outcome).
Difference-in-difference for MES
Difference-in-differences for secondary continuous measures: MES Bech-Rafaelsens Melancholia scale, MES .(Values 0- 44, higher scores mean a worse outcome).
Difference-in-differences for MADRS
Difference-in-differences for secondary continuous measures: MADRS Montgomery-Aaberg Depression Rating Scale, MADRS .(Values 0- 60, higher scores mean a worse outcome).
Difference-in-difference for YMRS
Difference-in-differences for secondary continuous measures:YMRS Young Mania Rating Scale, YMRS .(Values 0- 60, higher scores mean a worse outcome).
Difference-in-differences for ASRM-14
Difference-in-differences for secondary continuous measures:ASRM-14 Altman Self-Rating Mania Scale-14, .(Values 0- 56, higher scores mean a worse outcome).
Difference-in-differences for MDI
Difference-in-differences for secondary continuous measures:MDI Major Depression Inventory, MDI (Values 0- 58, higher scores mean a worse outcome).
Difference-in-differences for WHO-5 questionnaire
Difference-in-differences for secondary continuous measures: WHO-5 questionnaire. WHO-five Well-beeing Index, WHO-5 (Values 0- 100, higher scores mean a better outcome).
Difference-in-difference for SCIP
Difference-in-differences for secondary continuous measures: SCIP Screen for Cognitive Impairment in Psychiatry, SCIP (Values 0- 64+, higher scores mean a better outcome)
Difference-in-difference for COBRA
Difference-in-differences for secondary continuous measures: COBRA Cognitive complaints in bipolar disorder Ratings assessment, COBRA, (Values 0- 48, higher scores mean a worse outcome).
Difference-in-difference for FAST
Difference-in-differences for secondary continuous measures: FAST Functioning Assessment Short Test, FAST (Values 0 - 72, higher scores mean a worse outcome).
Difference-in-difference for PSQI
Difference-in-differences for secondary continuous measures:PSQI PIttsburgh Sleep Quality Index, PSQI (Values 0 - 21, higher scores mean a worse outcome).
Difference-in-difference for CGI-S
Difference-in-differences for secondary continuous measures: CGI-S Clinical Global Impression Scale - Severity, CGI-S (Values 1 -7, higher scores mean a worse outcome).
Difference-in-difference for CGI-I
Difference-in-differences for secondary continuous measures:CGI-I Clinical Global Impression Scale - Global Improvement CGI- I (Values 1 -7, higher scores mean a worse outcome).
Difference-in-difference for C-SSRS
Difference-in-differences for secondary continuous measures: C-SSRS Columbia-Suicide Severity Rating Scale, C-SSRS (Values 1 - 5, higher scores mean a worse outcome).
Difference-in-difference for accumulated benzodiazepine dose
Difference-in-differences for secondary continuous measures: accumulated benzodiazepine dose as diazepam equivalents (DSKP)
Difference-in-difference for time to all-causes discontinuation
Difference-in-differences for secondary continuous measures: for time to all-causes discontinuation
Difference-in-difference for time to all-causes. all-causes study endpoint.
Difference-in-differences for secondary continuous measures: all-causes study endpoint.
Between-group difference in reasons for time to all cause discontinuation.
Between-group difference for the ITT population in reasons for time to all cause discontinuation.
Between-group difference in reasons for treatment expectation.
Between-group difference for the ITT population in reasons for treatment expectation.
Between-group difference in reasons for adverse events.
Between-group difference for the ITT population in reasons for adverse events.
Between-group difference in reasons for serious adverse events.
Between-group difference for the ITT population in reasons for serious adverse events.

Full Information

First Posted
March 29, 2023
Last Updated
June 19, 2023
Sponsor
Aalborg University Hospital
Collaborators
Mental Health Center, Glostrup, Mental Health Center North Zealand, Mental Health Department Odense, University Clinic, Psychiatric Center Copenhagen, Rigshospitalet
search

1. Study Identification

Unique Protocol Identification Number
NCT05913947
Brief Title
Lithium Versus Cariprazine in the Acute Phase Treatment of Bipolar Depression (DUAG9)
Acronym
DUAG9
Official Title
Lithium Versus Cariprazine in the Acute Phase Treatment of Bipolar Depression: a Pragmatic Head-to-head Open, Randomized Multicenter Study: The 9th Study of the Danish University Antidepressant Group (DUAG 9)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 13, 2022 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Aalborg University Hospital
Collaborators
Mental Health Center, Glostrup, Mental Health Center North Zealand, Mental Health Department Odense, University Clinic, Psychiatric Center Copenhagen, Rigshospitalet

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
The goal is to study the effect of lithium compared to cariprazine in patients with depression in a bipolar disease. The main question it aims to answer is: Difference in change between the two groups from baseline to after 8 weeks treatment on Hamilton Ratings Scale for Depression, 6-item version (HDS-6) Participants will be randomized to treatment with either lithium or cariprazin. Will meet for interview and ratings 4 times during study period. In two meetings, there will be made blood samples and ECG. At one meeting also a Urine sample. Will be contacted for telephone interviews at 6 occasions.
Detailed Description
The primary aim is to investigate whether cariprazine is superior to lithium or vice versa in the acute treatment of patients with bipolar type 1 or 2 in a current depressive episode measured as change on the Hamilton Depression Scale, 6 item version (HDS-6) from baseline to 8 weeks of treatment. Secondarily, we aimed at comparing the two study medications on various other clinically relevant variables. These include depressive and manic symptomatology, sleep patterns, general well-being, cognitive function, social functioning and suicidal ideation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression, Bipolar

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
122 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Lithium
Arm Type
Experimental
Arm Description
Lithium citrate from 12 mmol increased to result in af 12-hour se-lithium between 0.6 and 0.8 mmol/l
Arm Title
Cariprazine
Arm Type
Experimental
Arm Description
Cariprazine from 1.5 mg to 3 mg daily in a single dose.
Intervention Type
Drug
Intervention Name(s)
Lithium
Other Intervention Name(s)
Litarex, ATC; N05AN01
Intervention Description
The starting dose (day one) of lithium citrate is 12 mmol (one tablet of lithium citrate contains 6 mmol lithium) given once a day before bedtime. On day three the dose is increased to 18 mmol. Dose adjustments are permitted after 7 days in a flexible manner to result in a 12-hour se-lithium between 0.6 and 0.8 mmol/l, aiming for the upper limit at the treating physician's discretion.
Intervention Type
Drug
Intervention Name(s)
Cariprazine
Other Intervention Name(s)
Reagila, ATC: N05AX15
Intervention Description
The starting dose for cariprazine is 1.5 mg daily in a single dose, and subsequently, after a minimum of two weeks, the dose can be increased to 3 mg and decreased again to 1.5 mg daily at the treating physician's discretion.
Primary Outcome Measure Information:
Title
Change in Hamilton Depressions scale, version 6 (HDS-6)
Description
The primary aim is to investigate whether cariprazine is superior to lithium or vice versa in the acute treatment of patients with bipolar type 1 or 2 in a current depressive episode measured as change on the Hamilton Depression Scale, 6 item version, HDS-6. (Values 0- 22, higher scores mean a worse outcome).
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Difference-in-difference for HDS-17
Description
Difference-in-differences for secondary continuous measures: Hamilton Depression Scale, 17 item version, HDS-17. (Values 0- 52, higher scores mean a worse outcome)
Time Frame
Week 4 and 8
Title
Difference-in-differences in HDS-6 for the PP 8 population
Description
Difference-in-differences (baseline to 8 weeks) in HDS-6 for the PP 8 population. Hamilton Depression Scale, 6 item version, HDS-6. (Values 0- 22, higher scores mean a worse outcome).
Time Frame
8 weeks
Title
Between-groups difference in proportion of responders and remitters in HDS-6 Scores.
Description
Between-groups difference in proportion of responders and remitters at week 4 and 8 in HDS-6 scores. Hamilton Depression Scale, 6 item version, HDS-6. (Values 0- 22, higher scores mean a worse outcome).
Time Frame
Week 4 and week 8
Title
Between-groups difference in proportion of responders and remitters
Description
Between-groups difference in proportion of responders and remitters with response and remission defined by HDS-6 score without clinical relevant manic symptoms (MAS <7) at planned or premature endpoint. Hamilton Depression Scale, 6 item version, HDS-6. (Values 0- 22, higher scores mean a worse outcome).
Time Frame
Week 4 and 8
Title
Between-groups difference in the proportion of patients with 'acceptable wellbeing'
Description
Between-groups difference in the proportion of patients with 'acceptable wellbeing', defined as the subject reporting ≥50 on the WHO-5 questionnaire at endpoint. WHO-five Well-being Index, WHO-5 (Values 0- 100, higher scores mean a better outcome).
Time Frame
up to 8 weeks
Title
Between-groups difference in proportion of switches to mania/hypomania.
Description
Between-groups difference in proportion of switches to mania/hypomania with or without mixed features, defined as mania/hypomania after DSM-5 or symptoms requiring treatment (switch or response occurring at any time in the study period)
Time Frame
up to 8 weeks
Title
Between-groups difference in "(switch to mania or hypomania) / (response) -ratio",
Description
Between-groups difference in "(switch to mania or hypomania) / (response) -ratio", defined as the number of subjects switching to mania or hypomania (as defined above) divided by the total number of responders, including those responders switching to mania
Time Frame
up to 8 weeks
Title
Between-group differences in reason for and time to all cause treatment discontinuation
Description
Between-group differences in reason for and time to all cause treatment discontinuation (lack of effect, lack of tolerability, lost to follow-up, or other cause).
Time Frame
up to 8 weeks
Title
Between-group difference in treatment compliance.
Description
Between-group difference in treatment compliance. Treatment compliance is defined as the proportion of received treatments out of the planned until drop-out or end of study.
Time Frame
up to 8 weeks
Title
Between-group difference in reasons for premature discontinuation
Description
Between-group difference for the ITT population in reasons for premature discontinuation
Time Frame
up to 8 weeks
Title
Difference-in-difference for MAS
Description
Difference-in-differences for secondary continuous measures: MAS Bech-Rafaelsens Mania scale .(Values 0- 44, higher scores mean a worse outcome).
Time Frame
Week 4 and 8
Title
Difference-in-difference for MES
Description
Difference-in-differences for secondary continuous measures: MES Bech-Rafaelsens Melancholia scale, MES .(Values 0- 44, higher scores mean a worse outcome).
Time Frame
Week 4 and 8
Title
Difference-in-differences for MADRS
Description
Difference-in-differences for secondary continuous measures: MADRS Montgomery-Aaberg Depression Rating Scale, MADRS .(Values 0- 60, higher scores mean a worse outcome).
Time Frame
Week 4 and 8
Title
Difference-in-difference for YMRS
Description
Difference-in-differences for secondary continuous measures:YMRS Young Mania Rating Scale, YMRS .(Values 0- 60, higher scores mean a worse outcome).
Time Frame
Week 4 and 8
Title
Difference-in-differences for ASRM-14
Description
Difference-in-differences for secondary continuous measures:ASRM-14 Altman Self-Rating Mania Scale-14, .(Values 0- 56, higher scores mean a worse outcome).
Time Frame
Week 4 and 8
Title
Difference-in-differences for MDI
Description
Difference-in-differences for secondary continuous measures:MDI Major Depression Inventory, MDI (Values 0- 58, higher scores mean a worse outcome).
Time Frame
Week 4 and 8
Title
Difference-in-differences for WHO-5 questionnaire
Description
Difference-in-differences for secondary continuous measures: WHO-5 questionnaire. WHO-five Well-beeing Index, WHO-5 (Values 0- 100, higher scores mean a better outcome).
Time Frame
Week 4 and 8
Title
Difference-in-difference for SCIP
Description
Difference-in-differences for secondary continuous measures: SCIP Screen for Cognitive Impairment in Psychiatry, SCIP (Values 0- 64+, higher scores mean a better outcome)
Time Frame
Week 8
Title
Difference-in-difference for COBRA
Description
Difference-in-differences for secondary continuous measures: COBRA Cognitive complaints in bipolar disorder Ratings assessment, COBRA, (Values 0- 48, higher scores mean a worse outcome).
Time Frame
Week 8
Title
Difference-in-difference for FAST
Description
Difference-in-differences for secondary continuous measures: FAST Functioning Assessment Short Test, FAST (Values 0 - 72, higher scores mean a worse outcome).
Time Frame
Week 4 and 8
Title
Difference-in-difference for PSQI
Description
Difference-in-differences for secondary continuous measures:PSQI PIttsburgh Sleep Quality Index, PSQI (Values 0 - 21, higher scores mean a worse outcome).
Time Frame
Week 4 and 8
Title
Difference-in-difference for CGI-S
Description
Difference-in-differences for secondary continuous measures: CGI-S Clinical Global Impression Scale - Severity, CGI-S (Values 1 -7, higher scores mean a worse outcome).
Time Frame
Week 4 and 8
Title
Difference-in-difference for CGI-I
Description
Difference-in-differences for secondary continuous measures:CGI-I Clinical Global Impression Scale - Global Improvement CGI- I (Values 1 -7, higher scores mean a worse outcome).
Time Frame
Week 4 and 8
Title
Difference-in-difference for C-SSRS
Description
Difference-in-differences for secondary continuous measures: C-SSRS Columbia-Suicide Severity Rating Scale, C-SSRS (Values 1 - 5, higher scores mean a worse outcome).
Time Frame
Week 4 and 8
Title
Difference-in-difference for accumulated benzodiazepine dose
Description
Difference-in-differences for secondary continuous measures: accumulated benzodiazepine dose as diazepam equivalents (DSKP)
Time Frame
Up to 8 weeks
Title
Difference-in-difference for time to all-causes discontinuation
Description
Difference-in-differences for secondary continuous measures: for time to all-causes discontinuation
Time Frame
Up to 8 weeks
Title
Difference-in-difference for time to all-causes. all-causes study endpoint.
Description
Difference-in-differences for secondary continuous measures: all-causes study endpoint.
Time Frame
Up to 8 weeks
Title
Between-group difference in reasons for time to all cause discontinuation.
Description
Between-group difference for the ITT population in reasons for time to all cause discontinuation.
Time Frame
Up to 8 weeks
Title
Between-group difference in reasons for treatment expectation.
Description
Between-group difference for the ITT population in reasons for treatment expectation.
Time Frame
Up to 8 weeks
Title
Between-group difference in reasons for adverse events.
Description
Between-group difference for the ITT population in reasons for adverse events.
Time Frame
Up to 8 weeks
Title
Between-group difference in reasons for serious adverse events.
Description
Between-group difference for the ITT population in reasons for serious adverse events.
Time Frame
Up to 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: A diagnosis of bipolar disorder, type 1 or type 2, and a current episode of depression according to DSM-5 Severity of depression: A score of at least 21 on the self-reported Major Depression Inventory (MDI). No start or dose increase of psychotropic medication (except for benzodiazepines and benzodiazepine-like drugs (zopiclone, zolpidem, and melatonin)) in the two weeks prior to inclusion. No new start of formalized psychotherapy sessions, excluding psychoeducation, during the 4 weeks prior to inclusion. Age criteria: Subjects must be at least 18 years old and below 65 at the time of randomization. The duration of the current depressive episode must be between 4 and 52 weeks as judged by the investigator at the time of randomization. Clinical uncertainty regarding which of the alternatives, cariprazine and lithium, would be the better choice in the specific case. Female participants should be sterile or non-fertile or, in case of being fertile, they must have a negative pregnancy test AND use safe anticonception. Signed document of informed consent. Exclusion Criteria: Prior or ongoing acute treatment of a depressive episode lasting > 14 days with either lithium or cariprazine as judged by the investigator. ECT within the current depressive episode. A score of MAS > 6. A diagnosis of dementia. High risk of non-adherence at the investigator's discretion. Not understanding the Danish language as judged by the investigator Psychiatric coercion in the form of forced admission or detainment OR sentence to forensic psychiatric care. Presence of clinically relevant delusions, hallucinations or other psychotic symptoms as judged by the investigator. Suicidality according to C-SSRS with a positive response to question 4 or 5 or upon investigator's discretion. Medical conditions like cancer, kidney failure, epilepsy, deep brain stimulation device, or other medical conditions interfering with study the outcome and safety as judged by investigator's discretion. Current harmful use or dependency of alcohol or drugs according to DSM-5. Known allergy to any of the substances in the study medication.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sanne V. Hovgesen, MD
Phone
+45 25487706
Email
sanne.hovgesen@rn.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Simon Johnsen, MsN
Phone
+45 50589034
Email
simonjohnsen@rn.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
René E. Nielsen, Prof, MD,PhD
Organizational Affiliation
Psychiatry, Aalborg University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aalborg University Hospital
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sanne V. Hovgesen, MD
Phone
+45 29217805
Email
sanne.hovgesen@rn.dk
First Name & Middle Initial & Last Name & Degree
Simon Johnsen
Phone
+45 61395631
Email
simon.johnsen@rn.dk

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Lithium Versus Cariprazine in the Acute Phase Treatment of Bipolar Depression (DUAG9)

We'll reach out to this number within 24 hrs