Bipolar DisorderPhase 4FLAMENCT02389712
16-week Comparative Effectiveness Trial of Lamotrigine vs. Fluoxetine for Bipolar Depression
A Phase 4 study testing Lamotrigine and Fluoxetine in people with Bipolar Disorder, run by Mayo Clinic at 1 site in United States.
Trial summary
The FLAME Study is a 16-week clinical trial to study treatment with lamotrigine or fluoxetine in bipolar I, II and bipolar schizoaffective depressed adults. The purpose of the trial is to have a better understanding of whether individuals with a particular gene type and other inherited biological markers will have a… 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?
- Lamotrigine and Fluoxetine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2015to 23 May 2018
- 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
- Adult participants, age 18-65.
- Outpatients or inpatients with a diagnosis of bipolar I, II or schizoaffective bipolar disorder, depressed phase, non-psychotic, (DSM-5 criteria, Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders Module D confirmed)
- At least mild symptom severity of depression as defined by the Clinical Global Impression for Bipolar Disorder (CGI-BP, Spearing et al. 1997) >2.
- Bipolar I participants must be on conventional mood stabilizing treatment [lithium, divalproex or valproate, or an atypical antipsychotic]. Participants with a bipolar II disorder may pursue the FLAME Study as monotherapy.
- Negative urine pregnancy test.
- Participants not planning pregnancy in the near future (6 months).
- Negative urine toxicology screen (except cannabis).
- No evidence of clinically significant laboratory screening tests (complete blood count (CBC); electrolytes; thyroid stimulating hormone (TSH); creatinine/blood urea nitrogen, Aspartate Aminotransferase (AST)/ALT). Clinical laboratory evaluation within the last three months is acceptable.
Who cannot join
- Inability or unwilling to provide informed consent.
- Inability to understand English.
- Actively suicidal participants at screening or enrollment visit as defined by a response of 3 or 4 on question 4 of the Bipolar Inventory of Symptoms Scale (BISS).
- Active delusions or hallucinations defined as a score of 3 or 4 on the BISS question 40 (persecutory ideas) or 41 (delusions or hallucinations).
- Impaired insight as defined as a score of 3 or 4 on BISS question 42 (insight).
- Hypomania defined by a BISS manic subscore of ≥15.
Show all 17Show fewer
- Axis I or II comorbidity that by referring mental health professional and/or study psychiatrist is primary need of treatment. (This will be assessed by the site principal investigator, who has >10 years clinical experience with this population. Hospital discharge summaries and outpatient medical records may be reviewed (i.e., adequate trials of mood stabilizing treatments with minimal to no response, prominent self-injurious behavior in the absence of significant mood symptomatology, or atypical cycle patterns) to make this decision.
- Pregnant participants
- Unwilling or unable to taper any current antidepressant therapy
- Participants currently breastfeeding
- Female not practicing a reliable form of birth control (condom, intrauterine device (IUD), Depo-Provera injection)
- Due to lamotrigine pharmacokinetics, female subjects wishing to commence oral contraceptive therapy (OCT) within 3 months of enrollment date or anticipate discontinuing OCT during study (stable oral contraceptive therapy exception).
- History of active substance abuse disorder within the last 3 months (other than caffeine or cannabis)
- Participants with medical contraindications that preclude lamotrigine or fluoxetine treatment
- History of severe adverse reaction to lamotrigine and/or fluoxetine
- Current carbamazepine or oxcarbazepine treatment
- Unstable active medical illness
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 16-week Open Randomized Comparative Effectiveness Trial of Lamotrigine vs. Fluoxetine for Bipolar Depression: Pharmacogenomic and Biomarker Predictors of Response
The FLAME Study is a 16-week clinical trial to study treatment with lamotrigine or fluoxetine in bipolar I, II and bipolar schizoaffective depressed adults. The purpose of the trial is to have a better understanding of whether individuals with a particular gene type and other inherited biological markers will have a good response to fluoxetine or lamotrigine, or alternatively, would be more likely to have side effects to this medication.
Read the detailed description
Depression is the predominant prevailing mood state of bipolar disorder and it is associated with substantial morbidity and mortality. However, in comparison to acute mania, bipolar depression is understudied both from the standpoint of its pathophysiology as well as clinical trials and treatment development. Given the lack of evidence-based guidelines, clinicians and participants enter a treatment phase with little guidance.
The FLAME Study is a 16-week, open randomized comparative effectiveness trial evaluating genomic predictors and biomarkers of response and adverse events to treatment with lamotrigine (n=200) and fluoxetine (n=200) for bipolar I, II and bipolar schizoaffective depressed adults (18-65). Participants will be recruited over a 5-year period.
It is known that functionally significant genetic polymorphisms of pharmacokinetics and pharmacodynamic pathways can influence individual differences in repose to specific medications. We propose to evaluate the contribution of these pharmacogenomic variations to lamotrigine and fluoxetine treatment response and adverse events. We will correlate clinical phenotypes of response and adverse events to treatment with genotype and haplotype variations of drug metabolism, neurotransmitter biosynthesis, (metabolism, storage, release, reuptake), receptor and intracellular signaling-that have been previously implicated to either lamotrigine or fluoxetine. These initial steps will be complemented with genome-wide analysis (GWA), pathway analysis and other candidate gene studies.
Based on our results we aim to develop a translational treatment algorithm of bipolar depression that may help individualized treatment for bipolar depression. This algorithm for participants could potentially increase the likelihood of successful treatment interventions, deliver the "right treatment, for the right participant at the right time", and decrease the number of ineffective treatments and/or risk for serious adverse events.
- Conditions
- Bipolar Disorder
- Being tested
- Lamotrigine, Fluoxetine
- Keywords
- Bipolar Disorder, Mayo Clinic
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LamotrigineDrug
Also called Lamictal
Lamotrigine dosing: 25 mg daily x 2 weeks, 50 mg daily x 2 weeks, 100 mg daily x 2 weeks, 200 mg (100 mg bid)) x 4 weeks. If patient still has at least mild depressive symptoms, the dose can be increased to 300 mg daily for 2 weeks and 400 mg for 4 weeks. Dose will be held for treatment response and can be reduced for side effects.
FluoxetineDrug
Also called Prozac
Fluoxetine dosing: 20mg for month 1, 40mg for month 2, and if still depressed (CGI ≥ 3) 60mg for month 3 and 4. Lower doses of fluoxetine will be prescribed for those with side effects. For known Cytochrome P450 2D6 poor metabolizers, fluoxetine will not be dosed > 40mg.
| Study group | Role | What they receive |
|---|---|---|
| Lamotrigine | Active comparator | Subjects on this arm will be randomized to Lamotrigine. Receives: Drug: Lamotrigine |
| Fluoxetine | Active comparator | Subjects on this arm will be randomized to Fluoxetine. Receives: Drug: Fluoxetine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inventory for Depressive Symptoms
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2015 (estimated)
- Study startMar 2015
- Primary completion23 May 2018
- Study completion23 May 2018
Why it stopped: Difficulties with recruitment
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.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- J Willard and Alice S. Marriott Foundation
- Responsible party
- Principal investigator, Mark Frye, Mayo Clinic
- Investigators
- Mark A Frye, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02389712
- Sponsor's protocol ID
- 13-003545-1
- Other IDs
- UL1TR000135
- Acronym
- FLAME
- Status last verified
- Jun 2019
- First submitted
- 10 Mar 2015
- Last updated
- 19 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 16-week Open Randomized Comparative Effectiveness Trial of Lamotrigine vs. Fluoxetine for Bipolar Depression: Pharmacogenomic and Biomarker Predictors of Response
- ClinicalTrials.gov ID
- NCT02389712
- Acronym / sponsor ID
- FLAME / 13-003545-1
- Conditions
- Bipolar Disorder
- Keywords
- Bipolar Disorder, Mayo Clinic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulties with recruitment
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- J Willard and Alice S. Marriott Foundation
- Study start
- Mar 2015
- Primary completion
- 23 May 2018 (actual)
- Study completion
- 23 May 2018 (actual)
- First posted
- 17 Mar 2015 (estimated)
- Results
- Posted 11 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The FLAME Study is a 16-week clinical trial to study treatment with lamotrigine or fluoxetine in bipolar I, II and bipolar schizoaffective depressed adults. The purpose of the trial is to have a better understanding of whether individuals with a particular gene type and other inherited biological markers will have a good response to fluoxetine or lamotrigine, or alternatively, would be more likely to have side effects to this medication.
Detailed description
Depression is the predominant prevailing mood state of bipolar disorder and it is associated with substantial morbidity and mortality. However, in comparison to acute mania, bipolar depression is understudied both from the standpoint of its pathophysiology as well as clinical trials and treatment development. Given the lack of evidence-based guidelines, clinicians and participants enter a treatment phase with little guidance.
The FLAME Study is a 16-week, open randomized comparative effectiveness trial evaluating genomic predictors and biomarkers of response and adverse events to treatment with lamotrigine (n=200) and fluoxetine (n=200) for bipolar I, II and bipolar schizoaffective depressed adults (18-65). Participants will be recruited over a 5-year period.
It is known that functionally significant genetic polymorphisms of pharmacokinetics and pharmacodynamic pathways can influence individual differences in repose to specific medications. We propose to evaluate the contribution of these pharmacogenomic variations to lamotrigine and fluoxetine treatment response and adverse events. We will correlate clinical phenotypes of response and adverse events to treatment with genotype and haplotype variations of drug metabolism, neurotransmitter biosynthesis, (metabolism, storage, release, reuptake), receptor and intracellular signaling-that have been previously implicated to either lamotrigine or fluoxetine. These initial steps will be complemented with genome-wide analysis (GWA), pathway analysis and other candidate gene studies.
Based on our results we aim to develop a translational treatment algorithm of bipolar depression that may help individualized treatment for bipolar depression. This algorithm for participants could potentially increase the likelihood of successful treatment interventions, deliver the "right treatment, for the right participant at the right time", and decrease the number of ineffective treatments and/or risk for serious adverse events.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lamotrigine | Active comparator | Drug: LamotrigineSubjects on this arm will be randomized to Lamotrigine. |
| Fluoxetine | Active comparator | Drug: FluoxetineSubjects on this arm will be randomized to Fluoxetine. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Adult participants, age 18-65.
- Outpatients or inpatients with a diagnosis of bipolar I, II or schizoaffective bipolar disorder, depressed phase, non-psychotic, (DSM-5 criteria, Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders Module D confirmed)
- At least mild symptom severity of depression as defined by the Clinical Global Impression for Bipolar Disorder (CGI-BP, Spearing et al. 1997) >2.
- Bipolar I participants must be on conventional mood stabilizing treatment [lithium, divalproex or valproate, or an atypical antipsychotic]. Participants with a bipolar II disorder may pursue the FLAME Study as monotherapy.
- Negative urine pregnancy test.
Key exclusion criteria (17 listed)
- Inability or unwilling to provide informed consent.
- Inability to understand English.
- Actively suicidal participants at screening or enrollment visit as defined by a response of 3 or 4 on question 4 of the Bipolar Inventory of Symptoms Scale (BISS).
- Active delusions or hallucinations defined as a score of 3 or 4 on the BISS question 40 (persecutory ideas) or 41 (delusions or hallucinations).
- Impaired insight as defined as a score of 3 or 4 on BISS question 42 (insight).
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 |
|---|---|---|
| LamotrigineAlso: LamictalLamotrigine dosing: 25 mg daily x 2 weeks, 50 mg daily x 2 weeks, 100 mg daily x 2 weeks, 200 mg (100 mg bid)) x 4 weeks. If patient still has at least mild depressive symptoms, the dose can be increased to 300 mg daily for 2 weeks and 400 mg for 4 weeks. Dose will be held for treatment response and can be reduced for side effects. | Drug | Lamotrigine |
| FluoxetineAlso: ProzacFluoxetine dosing: 20mg for month 1, 40mg for month 2, and if still depressed (CGI ≥ 3) 60mg for month 3 and 4. Lower doses of fluoxetine will be prescribed for those with side effects. For known Cytochrome P450 2D6 poor metabolizers, fluoxetine will not be dosed > 40mg. | Drug | Fluoxetine |
Primary outcome
Inventory for Depressive Symptoms
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Mark A Frye, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lamotrigine and Fluoxetine in people with Bipolar Disorder, run by Mayo Clinic at 1 site in United States.
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 8 inclusion and 17 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: stopped early, as of the sponsor's last update on 19 Jun 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 United States. 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. 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 11 Jun 2019). 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?
Inventory for Depressive Symptoms (time frame: 12 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 19 Jun 2019.