Depression, BipolarPhase 2/3TDCS-BDNCT02152878
Transcranial Direct Current Stimulation for the Treatment of Bipolar Depression
A Phase 2/3 study testing Active stimulation in people with Depression, Bipolar, run by University of Sao Paulo at 1 site in Brazil.
Trial summary
Non-invasive brain stimulation therapies have been increasingly investigated in recent years as a treatment for neuropsychiatric disorders, particularly mood disorders. They are particularly appealing since many patients are either refractory or present side effects to standard pharmacological regimens. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Depression, Bipolar
- What is being tested?
- Active stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteBrazil
- Study dates
- Apr 2014to Nov 2016
- Phase
- Phase 2/3
- 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
- bipolar depressed (type I, II or not otherwise specified) participants with symptoms in spite of an adequate treatment course with mood stabilizers.
- the depressive episode has to be of at least moderate intensity (baseline HDRS>=16)
- read and understand Portuguese
Who cannot join
- other neuropsychiatric conditions, such as schizophrenia, substance dependence, dementias, traumatic brain injury, epilepsy and so forth (although participants with anxiety disorders can be included whether the primary diagnosis is BDD);
- mixed states, defined as simultaneously presenting (hypo)manic symptoms with a Young Manic Rating Scale (YMRS) > 8;
- pregnancy;
- specific contra-indications to tDCS;
- severe/life-threatening clinical conditions. Participants will have to be drug-free or at stable drug regimen for at least 6 weeks prior to trial onset. Benzodiazepine drugs will be allowed, although only at low doses (less than 20mg/day of diazepam or equivalent).
Trial locations and contacts
1 site in 1 country.
About this study
Non-invasive brain stimulation therapies have been increasingly investigated in recent years as a treatment for neuropsychiatric disorders, particularly mood disorders. They are particularly appealing since many patients are either refractory or present side effects to standard pharmacological regimens. TDCS (transcranial direct current stimulation). a novel non- pharmacological brain stimulation technique, might help in overcoming some of these issues, since it has low cost, high portability and it is relatively easy to use. TDCS consists in applying a weak, direct current through two electrodes placed over the scalp; the anode and the cathode increasing and decreasing cortical excitability during and beyond the period of stimulation. It is also a safe technique with only mild adverse effects described. Previous studies, some of them from our group, have described that tDCS is an effective technique for major depression. However, the role of tDCS as a treatment for bipolar depression (BD) has been insufficiently investigated. Therefore, our aim is to address the antidepressant effects of tDCS in BD in a randomized, sham- controlled trial in a refractory sample.
Read the detailed description
BD represents the greatest burden on patients with bipolar disorder, since the depressive episodes are the most frequent and also particularly associated with suicide 7. BD treatment is controversial, with some stricter guidelines recommending only lithium, lamotrigine and quetiapine as a first-treatment, whereas others allow the use of antidepressants (which can increase manic switch and should be used in association with mood stabilizers) and other anticonvulsants and antipsychotics 8. For refractory BD the available level I evidence is very scarce, with only seven studies exploring this issue hitherto 9. Therefore, the importance of this study proposal is justified considering the burden of the disease, the paucity of current therapeutic studies and the promising results presented for tDCS in unipolar disorder.
- Conditions
- Depression, Bipolar
- Being tested
- Sham stimulation, Active stimulation
- Keywords
- transcranial direct current stimulation, non invasive brain stimulation, bipolar disorder, depression
- Medical subject headings
- Bipolar Disorder, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sham stimulationDevice
Also called TDCS
For sham tDCS, the device will be turned off after 30 seconds of stimulation.
Active stimulationDevice
For active tDCS, we will place the anode and the cathode over the left and right dorsolateral prefrontal cortex areas, respectively (corresponding to F3 and F4 according to the EEG 10-20 system). We will use 5x5 cm electrodes and a 2mA current for 30 minutes per day. This montage is known as "bifrontal" setup and has been previously used in major depression trials
| Study group | Role | What they receive |
|---|---|---|
| Active stimulation | Active comparator | Active stimulation (tDCS) will be used in the dose of 2mA /30 min per day, for 10 days and two extra sessions every other week (total of 12 sessions). Receives: Device: Active stimulation |
| Sham stimulation | Placebo comparator | For Sham Transcranial Direct Current Stimulation, the device is automatically turned off after 30 seconds of stimulation and remains turned off. Receives: Device: Sham stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Hamilton Scale for Depression, 17 items
Continuous measure (score change)
Measured: week 0 (baseline), week 2, week 4 and week 6 (endpoint)
Secondary outcomes (1)
Change in Montgomery-Asberg Depression Rating Scale
Continuous measure (score changes)
Measured: week 0 (baseline), week 2, week 4 and week 6 (endpoint)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2014 (estimated)
- Study startApr 2014
- Primary completionJul 2016
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Depression, BipolarStudies of the same condition, open and under way.
- More trials run by University of Sao PauloThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- Brain & Behavior Research Foundation
- Responsible party
- Principal investigator, Andre Brunoni, University of Sao Paulo
- Investigators
- Andre R Brunoni, MD, PhD, Principal investigator, University of Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02152878
- Sponsor's protocol ID
- BETTER
- Acronym
- TDCS-BD
- Status last verified
- Nov 2016
- First submitted
- 29 May 2014
- Last updated
- 22 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Goerigk S, Cretaz E, Sampaio-Junior B, Vieira ELM, Gattaz W, Klein I, Lafer B, Teixeira AL, Carvalho AF, Lotufo PA, Bensenor IM, Buhner M, Padberg F, Brunoni AR. Effects of tDCS on neuroplasticity and inflammatory biomarkers in bipolar depression: Results from a sham-controlled study. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 8;105:110119. doi: 10.1016/j.pnpbp.2020.110119. Epub 2020 Oct 4.
PubMed 33022345Tortella G, Sampaio-Junior B, Moreno ML, Moffa AH, da Silva AF, Lafer B, Lotufo PA, Gattaz W, Borrione L, Machado-Vieira R, Goerigk S, Bensenor IM, Brunoni AR. Cognitive outcomes of the bipolar depression electrical treatment trial (BETTER): a randomized, double-blind, sham-controlled study. Eur Arch Psychiatry Clin Neurosci. 2021 Feb;271(1):93-100. doi: 10.1007/s00406-020-01121-2. Epub 2020 Mar 27.
PubMed 32221654Sampaio-Junior B, Tortella G, Borrione L, Moffa AH, Machado-Vieira R, Cretaz E, Fernandes da Silva A, Fraguas R, Aparicio LV, Klein I, Lafer B, Goerigk S, Bensenor IM, Lotufo PA, Gattaz WF, Brunoni AR. Efficacy and Safety of Transcranial Direct Current Stimulation as an Add-on Treatment for Bipolar Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Feb 1;75(2):158-166. doi: 10.1001/jamapsychiatry.2017.4040.
PubMed 29282470
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcranial Direct Current Stimulation for the Treatment of Bipolar Depression
- ClinicalTrials.gov ID
- NCT02152878
- Acronym / sponsor ID
- TDCS-BD / BETTER
- Conditions
- Depression, Bipolar
- Keywords
- transcranial direct current stimulation, non invasive brain stimulation, bipolar disorder, depression
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Collaborators
- Brain & Behavior Research Foundation
- Study start
- Apr 2014
- Primary completion
- Jul 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 2 Jun 2014 (estimated)
- 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.
Non-invasive brain stimulation therapies have been increasingly investigated in recent years as a treatment for neuropsychiatric disorders, particularly mood disorders. They are particularly appealing since many patients are either refractory or present side effects to standard pharmacological regimens. TDCS (transcranial direct current stimulation). a novel non- pharmacological brain stimulation technique, might help in overcoming some of these issues, since it has low cost, high portability and it is relatively easy to use. TDCS consists in applying a weak, direct current through two electrodes placed over the scalp; the anode and the cathode increasing and decreasing cortical excitability during and beyond the period of stimulation. It is also a safe technique with only mild adverse effects described. Previous studies, some of them from our group, have described that tDCS is an effective technique for major depression. However, the role of tDCS as a treatment for bipolar depression (BD) has been insufficiently investigated. Therefore, our aim is to address the antidepressant effects of tDCS in BD in a randomized, sham- controlled trial in a refractory sample.
Detailed description
BD represents the greatest burden on patients with bipolar disorder, since the depressive episodes are the most frequent and also particularly associated with suicide 7. BD treatment is controversial, with some stricter guidelines recommending only lithium, lamotrigine and quetiapine as a first-treatment, whereas others allow the use of antidepressants (which can increase manic switch and should be used in association with mood stabilizers) and other anticonvulsants and antipsychotics 8. For refractory BD the available level I evidence is very scarce, with only seven studies exploring this issue hitherto 9. Therefore, the importance of this study proposal is justified considering the burden of the disease, the paucity of current therapeutic studies and the promising results presented for tDCS in unipolar disorder.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active stimulation | Active comparator | Device: Active stimulationActive stimulation (tDCS) will be used in the dose of 2mA /30 min per day, for 10 days and two extra sessions every other week (total of 12 sessions). |
| Sham stimulation | Placebo comparator | Device: Sham stimulationFor Sham Transcranial Direct Current Stimulation, the device is automatically turned off after 30 seconds of stimulation and remains turned off. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- bipolar depressed (type I, II or not otherwise specified) participants with symptoms in spite of an adequate treatment course with mood stabilizers.
- the depressive episode has to be of at least moderate intensity (baseline HDRS>=16)
- read and understand Portuguese
Key exclusion criteria (5 listed)
- other neuropsychiatric conditions, such as schizophrenia, substance dependence, dementias, traumatic brain injury, epilepsy and so forth (although participants with anxiety disorders can be included whether the primary diagnosis is BDD);
- mixed states, defined as simultaneously presenting (hypo)manic symptoms with a Young Manic Rating Scale (YMRS) > 8;
- pregnancy;
- specific contra-indications to tDCS;
- severe/life-threatening clinical conditions. Participants will have to be drug-free or at stable drug regimen for at least 6 weeks prior to trial onset. Benzodiazepine drugs will be allowed, although only at low doses (less than 20mg/day of diazepam or equivalent).
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 |
|---|---|---|
| Sham stimulationAlso: TDCSFor sham tDCS, the device will be turned off after 30 seconds of stimulation. | Device | Sham stimulation |
| Active stimulationFor active tDCS, we will place the anode and the cathode over the left and right dorsolateral prefrontal cortex areas, respectively (corresponding to F3 and F4 according to the EEG 10-20 system). We will use 5x5 cm electrodes and a 2mA current for 30 minutes per day. This montage is known as "bifrontal" setup and has been previously used in major depression trials | Device | Active stimulation |
Primary outcome
Change in Hamilton Scale for Depression, 17 items
Time frame: week 0 (baseline), week 2, week 4 and week 6 (endpoint)
Continuous measure (score change)
1 secondary outcome
Change in Montgomery-Asberg Depression Rating Scale
Time frame: week 0 (baseline), week 2, week 4 and week 6 (endpoint)
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 22 Nov 2016.
- Derived from this study: PubMed 33022345Goerigk S, Cretaz E, Sampaio-Junior B, Vieira ELM, Gattaz W, Klein I, Lafer B, Teixeira AL, Carvalho AF, Lotufo PA, Bensenor IM, Buhner M, Padberg F, Brunoni AR. Effects of tDCS on neuroplasticity and inflammatory biomarkers in bipolar depression: Results from a sham-controlled study. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 8;105:110119. doi: 10.1016/j.pnpbp.2020.110119. Epub 2020 Oct 4.
- Derived from this study: PubMed 32221654Tortella G, Sampaio-Junior B, Moreno ML, Moffa AH, da Silva AF, Lafer B, Lotufo PA, Gattaz W, Borrione L, Machado-Vieira R, Goerigk S, Bensenor IM, Brunoni AR. Cognitive outcomes of the bipolar depression electrical treatment trial (BETTER): a randomized, double-blind, sham-controlled study. Eur Arch Psychiatry Clin Neurosci. 2021 Feb;271(1):93-100. doi: 10.1007/s00406-020-01121-2. Epub 2020 Mar 27.
- Derived from this study: PubMed 29282470Sampaio-Junior B, Tortella G, Borrione L, Moffa AH, Machado-Vieira R, Cretaz E, Fernandes da Silva A, Fraguas R, Aparicio LV, Klein I, Lafer B, Goerigk S, Bensenor IM, Lotufo PA, Gattaz WF, Brunoni AR. Efficacy and Safety of Transcranial Direct Current Stimulation as an Add-on Treatment for Bipolar Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Feb 1;75(2):158-166. doi: 10.1001/jamapsychiatry.2017.4040.
- Website of Interdisciplinary Neuromodulation ServiceLink provided by the sponsor.
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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.
Andre R Brunoni, MD, PhD principal investigator
University of Sao Paulo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Active stimulation in people with Depression, Bipolar, run by University of Sao Paulo at 1 site in Brazil.
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 3 inclusion and 5 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 22 Nov 2016. 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 Brazil. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Change in Hamilton Scale for Depression, 17 items (time frame: week 0 (baseline), week 2, week 4 and week 6 (endpoint)). 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 NCT02152878, which also lists 3 linked publications.
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 22 Nov 2016.