Bipolar DisorderPhase 4NCT02870283

Cost- Effectiveness and Quality of Life Assessment in Mood Disorder

A Phase 4 study testing Lithium, Valproic Acid and Carbamazepine in people with Bipolar Disorder, run by Federal University of Rio Grande do Sul.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

To evaluate the effectiveness of three systematic interventions for Bipolar Disorder (BD) mixed episodes using medications available in the Brazilian Public Healthcare System (SUS), and assessment of the quality of life of these patients. A randomized pragmatic trial was conducted. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Bipolar Disorder
What is being tested?: Lithium, Valproic Acid and Carbamazepine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 107 participants
Where: No sites listed yet
Study dates: May 2010to Sep 2015
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

ages between 18 and 65;
BD current acute mixed episode;
total capacity to understand and respond to self-applied instruments;
the presence of symptoms in the last 30 days;
abstinence for at least 30 days for drug addicts.

Who cannot join

presence of Organic Brain Syndrome (OBS);
pregnancy or lactation;
criteria for psychiatric hospitalization.

About this study

Official title: Assessment of Cost- Effectiveness Interventions and the Quality of Life in Patients With Mood Disorders Through Resources Available in Brazilian Public Health

A randomized pragmatic trial was conducted. An algorithm was developed for the treatment of episodes of bipolar mixed episodes.

Read the detailed description

The study design was that of a pragmatic randomized clinical trial to evaluate the effectiveness of treatments for mood disorders in a public healthcare context in the city of Porto Alegre, in southern Brazil. The algorithm was originally developed for the treatment of mixed episodes by a Delphi panel of experts from psychiatric associations in Brazil. All subjects provided an informed consent form, in writing, in order to participate in the study protocol, which was approved by the institutional ethics committee.

Procedures and measurements of the study

The subjects under evaluation were selected and they followed the stages defined by the treatment protocol:

Sample selection by being referred from the primary healthcare clinics in the municipality;
Informative talk about mood disorders and the research, with the informed consent forms being provided to the subjects;
Screening for BD mixed episodes with the use of the Patient Health Questionnaire (PHQ-9), and Hypomanic Symptoms Checklist Brazilian Version (HCL -32-BV);
Diagnostic evaluation through the Mini International Neuropsychiatric Interview (MINI) and clinical interview for individuals with positive results in the screening instruments;
Baseline and demographic assessments using standardized semi-structured interviews in the first and second visits;
In each clinic visit, the severity of the symptoms were evealuated using the Clinical Global Impression Scale (CGI), Hamilton Rating Scale for Depression (HRSD), and Young Manic Rating Scale (YMRS);
Biweekly follow-up, changed to monthly after stabilization - with a maximum follow-up period of 52 weeks.

Conditions: Bipolar Disorder
Being tested: Lithium, Valproic Acid, Carbamazepine
Keywords: Cost effectiveness, Bipolar disorder, Mixed episodes, Quality of life
Medical subject headings: Bipolar Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LithiumDrug
Also called carbolitium
Valproic AcidDrug
Also called depakene
CarbamazepineDrug
Also called tegretol

Study groups in NCT02870283
Study group	Role	What they receive
Lithium	Active comparator	Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine). Group (A) Started Lithium (900mg-1500mg) Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks. 1. First step: Monotherapy with Lithium (900-1500mg) Non responsive patients: 2nd step. 2. Second step: Randomization for lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) OR lithium (900mg-1500mg) + carbamazepine (600mg-1200mg). Non responsive patients: 3rd step. 3. Third step: Crossover lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) X lithium (900mg-1500mg) + carbamazepine (600mg-1200mg). Non responsive patients: 4th step. 4. Fourth step: Association with risperidone (1-6mg) Receives: Drug: Lithium
Acid Valproic	Active comparator	Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine). Group (B) Started Valproic Acid (1000mg-1500mg). Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks. 1. First step: Monotherapy with Valproic Acid (1000mg-1500mg) Non responsive patients: 2nd step. 2. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step. 3. Third step: Crossover: lithium (900mg-1500mg) + carbamazepine (600mg-1200mg). Non responsive patients: 4th step. 4. Fourth step: Association with risperidone (1-6mg) Receives: Drug: Valproic Acid
Carbamazepine	Active comparator	Subjects were randomized into three groups: (lithium, valproic acid, or carbamazepine). Group (C) Started Carbamazepine (600mg-1200mg). Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks. 1. First step: Monotherapy with Carbamazepine (600mg-1200mg). Non responsive patients: 2nd step. 2. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step. 3. Third step: Crossover: lithium (900mg-1500mg) + valproic acid (1000mg-1500mg). Non responsive patients: 4th step. 4. Fourth step: Association with risperidone (1-6mg) Receives: Drug: Carbamazepine

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Response to Treatment"
Response to treatment was defined as a 50% reduction from baseline scores in Hamilton Rating Scale for Depression (HRSD)and Young Mania Rating Scale (YMRS) scales HRSD was developed to evaluate and quantify depression.Its abbreviated version,. Scoring is based on the 17-item scale and scores of 0-7 are considered as being normal. The cutoff points are: 8-17 for mild depression,18-24 for moderate depression, and 25 or more for severe depression. The maximum score being 52 on the 17-point scale.
YMRS is is the most widely used assessment tool for manic symptoms. The scale consists of 11 items .The YMRS follows the style of the Hamilton Rating Scale for Depression (HAM-D) with each item given a severity rating. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/agressive behavior), while the remaining seven items are graded on a 0 to 4 scale. Scores of YMRS > 20 generates indicate mania
Measured: 8 weeks

Secondary outcomes (2)

Number of Participants With Remission to Treatment
The remission outcome was established as obtaining three consecutive visits with scores of values considered asymptomatic Hamilton Rating Scale for Depression(HRSD <7 points) and Young Mania Rating Scale (YMRS <6 points) during the trial. The subjects that were asymptomatic for at least 6-8 month were considered to be in partial remission and complete if at least 12 months without symptoms, according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).
Measured: 8 months
Quality of Life - WHOQOL Bref Intrument
Quality of Life - WHOQOL -BREF instrument scores scores 0-20 . higher scores mean a better outcome. The quality of life was assessed for entire algorithm. There were no comparisons between each arms of the study.
Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2010Sep 2015

First posted17 Aug 2016 (estimated)
Study startMay 2010
Primary completionNov 2014
Study completionSep 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Bipolar 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 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 107 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02870283
Sponsor's protocol ID: 09-013
Status last verified: Aug 2016
First submitted: 26 May 2016
Last updated: 20 Nov 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

Lima AF, Miguel SR, Cohen M, Zimmermann JJ, Shansis FM, Cruz LN, Ziegelmann PK, Polanczyk CA, Fleck MP. Effectiveness evaluation of mood disorder treatment algorithms in Brazilian public healthcare patients. Braz J Psychiatry. 2018 Jan-Mar;40(1):26-34. doi: 10.1590/1516-4446-2016-2147. Epub 2017 Aug 21.
PubMed 28832750

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Safety and Feasibility of DBS for Bipolar Depression
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All Bipolar Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 20 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Assessment of Cost- Effectiveness Interventions and the Quality of Life in Patients With Mood Disorders Through Resources Available in Brazilian Public Health
ClinicalTrials.gov ID: NCT02870283
Acronym / sponsor ID: 09-013
Conditions: Bipolar Disorder
Keywords: Cost effectiveness, Bipolar disorder, Mixed episodes, Quality of life
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 107 participants (actual)
Lead sponsor: Federal University of Rio Grande do SulUniversity, hospital or other
Study start: May 2010
Primary completion: Nov 2014 (actual)
Study completion: Sep 2015 (actual)
First posted: 17 Aug 2016 (estimated)
Results: Posted 2 Sep 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

A randomized pragmatic trial was conducted. An algorithm was developed for the treatment of episodes of bipolar mixed episodes.

Detailed description

Procedures and measurements of the study

The subjects under evaluation were selected and they followed the stages defined by the treatment protocol:

Sample selection by being referred from the primary healthcare clinics in the municipality;
Informative talk about mood disorders and the research, with the informed consent forms being provided to the subjects;
Screening for BD mixed episodes with the use of the Patient Health Questionnaire (PHQ-9), and Hypomanic Symptoms Checklist Brazilian Version (HCL -32-BV);
Diagnostic evaluation through the Mini International Neuropsychiatric Interview (MINI) and clinical interview for individuals with positive results in the screening instruments;
Baseline and demographic assessments using standardized semi-structured interviews in the first and second visits;
In each clinic visit, the severity of the symptoms were evealuated using the Clinical Global Impression Scale (CGI), Hamilton Rating Scale for Depression (HRSD), and Young Manic Rating Scale (YMRS);
Biweekly follow-up, changed to monthly after stabilization - with a maximum follow-up period of 52 weeks.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Lithium	Active comparator	Drug: LithiumSubjects were randomized into three groups: (lithium, valproic acid, or carbamazepine). Group (A) Started Lithium (900mg-1500mg) Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks. 1. First step: Monotherapy with Lithium (900-1500mg) Non responsive patients: 2nd step. 2. Second step: Randomization for lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) OR lithium (900mg-1500mg) + carbamazepine (600mg-1200mg). Non responsive patients: 3rd step. 3. Third step: Crossover lithium (900mg-1500mg) + valproic acid (1000mg-1500mg) X lithium (900mg-1500mg) + carbamazepine (600mg-1200mg). Non responsive patients: 4th step. 4. Fourth step: Association with risperidone (1-6mg)
Acid Valproic	Active comparator	Drug: Valproic AcidSubjects were randomized into three groups: (lithium, valproic acid, or carbamazepine). Group (B) Started Valproic Acid (1000mg-1500mg). Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks. 1. First step: Monotherapy with Valproic Acid (1000mg-1500mg) Non responsive patients: 2nd step. 2. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step. 3. Third step: Crossover: lithium (900mg-1500mg) + carbamazepine (600mg-1200mg). Non responsive patients: 4th step. 4. Fourth step: Association with risperidone (1-6mg)
Carbamazepine	Active comparator	Drug: CarbamazepineSubjects were randomized into three groups: (lithium, valproic acid, or carbamazepine). Group (C) Started Carbamazepine (600mg-1200mg). Subjects evaluated for responsiveness every 2 weeks. Responsive to treatment patients remain in the same step. Max. step duration of 8 weeks. 1. First step: Monotherapy with Carbamazepine (600mg-1200mg). Non responsive patients: 2nd step. 2. Second step: Association with lithium (900mg-1500mg). Non responsive patients: 3rd step. 3. Third step: Crossover: lithium (900mg-1500mg) + valproic acid (1000mg-1500mg). Non responsive patients: 4th step. 4. Fourth step: Association with risperidone (1-6mg)

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

ages between 18 and 65;
BD current acute mixed episode;
total capacity to understand and respond to self-applied instruments;
the presence of symptoms in the last 30 days;
abstinence for at least 30 days for drug addicts.

Key exclusion criteria (3 listed)

presence of Organic Brain Syndrome (OBS);
pregnancy or lactation;
criteria for psychiatric hospitalization.

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
LithiumAlso: carbolitium	Drug	Lithium
Valproic AcidAlso: depakene	Drug	Acid Valproic
CarbamazepineAlso: tegretol	Drug	Carbamazepine

Primary outcome

Number of Participants With Response to Treatment"
Time frame: 8 weeks
Response to treatment was defined as a 50% reduction from baseline scores in Hamilton Rating Scale for Depression (HRSD)and Young Mania Rating Scale (YMRS) scales HRSD was developed to evaluate and quantify depression.Its abbreviated version,. Scoring is based on the 17-item scale and scores of 0-7 are considered as being normal. The cutoff points are: 8-17 for mild depression,18-24 for moderate depression, and 25 or more for severe depression. The maximum score being 52 on the 17-point scale. YMRS is is the most widely used assessment tool for manic symptoms. The scale consists of 11 items .The YMRS follows the style of the Hamilton Rating Scale for Depression (HAM-D) with each item given a severity rating. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/agressive behavior), while the remaining seven items are graded on a 0 to 4 scale. Scores of YMRS > 20 generates indicate mania

2 secondary outcomes

Number of Participants With Remission to Treatment
Time frame: 8 months
Quality of Life - WHOQOL Bref Intrument
Time frame: 12 weeks

Results and safety

Results posted to the registry on 2 Sep 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lithium	38	35
Acid Valproic	35	26
Carbamazepine	34	15

Primary outcome: Number of Participants With Response to Treatment"

Time frame: 8 weeks. Count of participants. Unit: Participants

Measure	Lithium n = 38	Acid Valproic n = 35	Carbamazepine n = 34
Value	31	28	27

2 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lithium	0 of 38 (0%)	0 of 38 (0%)	0 of 38
Acid Valproic	0 of 35 (0%)	0 of 35 (0%)	0 of 35
Carbamazepine	0 of 34 (0%)	0 of 34 (0%)	0 of 34

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28832750Lima AF, Miguel SR, Cohen M, Zimmermann JJ, Shansis FM, Cruz LN, Ziegelmann PK, Polanczyk CA, Fleck MP. Effectiveness evaluation of mood disorder treatment algorithms in Brazilian public healthcare patients. Braz J Psychiatry. 2018 Jan-Mar;40(1):26-34. doi: 10.1590/1516-4446-2016-2147. Epub 2017 Aug 21.
Individual participant dataSharing planned: No

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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.

Marcelo Fleck, PhD principal investigator

Federal University of Rio Grande do Sul

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Lithium, Valproic Acid and Carbamazepine in people with Bipolar Disorder, run by Federal University of Rio Grande do Sul.

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 5 inclusion and 3 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 20 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Response to Treatment" (time frame: 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02870283, which also lists 1 linked publication.

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 20 Nov 2020.