Bipolar DisorderNCT03603561
Continuous Theta Burst Stimulation as an add-on Treatment for Bipolar Depression
A study testing cTBS in people with Bipolar Disorder and Bipolar Depression, run by Universiteit Antwerpen at 2 sites in Belgium.
Trial summary
This study aims to investigate the clinical efficacy of continuous theta burst stimulation (cTBS) on the right DLPFC as an add-on treatment in bipolar depression. The study consists of three phases. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Bipolar Disorder, Bipolar Depression, Bipolar I Disorder
- What is being tested?
- cTBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 2 sitesBelgium
- Study dates
- 1 Aug 2018to Jul 2020
- Phase
- Interventional
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnostic and Statistical Manual-IV defined bipolar subjects (bipolar types I and II), depressed or mixed phase, confirmed by the Mini-International Neuropsychiatric Interview (MINI-plus 5.0.0.)
- Hamilton Rating Scale for Depression-17 score of 17 or more.
- Stable psychotropic medication regimen for at least 2 weeks prior to randomization and patient is willing to remain on a stable regimen from screening (S) after the second measurement point T2 (2 to 3 weeks).
- Antidepressants:
- On stable antidepressant treatment for 4 weeks.
- Stable antidepressant medication but dose has been recently changed (higher/lower dose): duration of 2 weeks should lie between change of medication dose and screening (S).
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- If the patient recently stopped the antidepressant treatment, a wash-out period of 14 days is necessary.
- Mood stabilizers:
- On a stable dose of mood-stabilizing medication (e.g., lithium, valproate, carbamazepine, lamotrigine, antipsychotic agents) for at least 4 weeks. In case of change in dose of the mood stabilizing medication, participants can be included given that no or minimal improvement is seen after 2 weeks of dosing.
- Atypical antipsychotics
- On a stable dose of for at least 4 weeks. In case of change in dose of antipsychotics, participants can be included given that no or minimal improvement is seen after 2 weeks of dosing.
- Benzodiazepines are permitted to a maximum allowed dose of equivalent of 40 mg diazepam. If the dosage has been recently changed: stable dose during 2 weeks.
- Able to read, understand and sign the Informed Consent Form.
Who cannot join
- Contra-indications for TMS treatment:
- Current or past history of epilepsy.
- The risk of seizure with any reasons.
- Organic brain damage (for example mass brain lesions, cerebrovascular accident, …).
- Neurosurgical interventions.
- Having a pacemaker or metal or magnetic objects in the brain.
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- Unipolar depression
- Psychotic disorder (MINI-plus 5.0.0; DSM-IV codes 295.10, 295.20, .30, .40, .60, .70, .90, 297.10, 298.90); exceptions are: depression with psychotic features MINI-Plus 5.0.0; DSM code 296.23)
- Current alcohol dependence (MINI-plus 5.0.0. DSM IV code 303.9) (in the last year)
- Current substance abuse or dependence (DSM-IV codes 304.00-.90, 305.20 -.70) (in the last year), with the exception of nicotine and caffeine (DSM IV codes 305.10 and 305.90)
- Suicide attempt within 6 months before the start of the study
- Pregnancy or lactation
Trial locations and contacts
2 sites in 1 country.
Belgium2 sites, 2 recruiting
- Not yet recruiting
University Hospital of Brussels
Brussels, 1000
Chris Baeken, PhD, 9 332 43 94 ext. +32, chris.baeken@uzbrussel.be
Dieter Zeeuws, MD, 2 477 60 12 ext. +32, dieter.zeeuws@uzbrussel.be
- Recruiting
University Psychiatric Hospital Duffel
Duffel, 2570
Kaat Hebbrecht, Dr, 15304048 ext. +32, kaat.hebbrecht@emmaus.be
Bernard Sabbe, PhD, 15304034 ext. +32, bernard.sabbe@ua.ac.be
About this study
Official title: Continuous Theta Burst Transcranial Magnetic Stimulation as an add-on Treatment for Bipolar Depression: a Multicenter Randomized Sham-controlled Trial
This study aims to investigate the clinical efficacy of continuous theta burst stimulation (cTBS) on the right DLPFC as an add-on treatment in bipolar depression. The study consists of three phases.
Phase 1: Bipolar depressed patients will be selected by a certified psychiatrist, who will administer (semi-)structured clinical interviews (M.I.N.I.-Plus 5.0.0, HRSD-17). The presence of exclusion criteria will be evaluated. Eligible patients will undergo MRI brain imaging for TMS neuronavigation
Read more
Phase 2: Baseline clinical, cognitive and psychomotor assessments will take place. Patients will also undergo blood samples for laboratory and research assessments.
TBS involves applying triple-pulse 50 Hz bursts given at a rate of 5 Hz uninterrupted trains (1). Patients will be treated with in total 20 continuous Theta Burst Stimulation (cTBS) session (900 pulses per session) over the right dorsolateral prefrontal cortex, which will be spread over 4 days. A stimulation intensity of 100% of the subject's resting motor threshold (rMT) of the right abductor pollicis brevis muscle will used.
Patients will be randomized to receive either the real cTBS or sham treatment. Sham stimulation will be applied with a sham coil. The sham coil produces identical sounds but is not associated with a stimulus sensation compared to the coil delivering real stimulation cTBS. The investigators expect that real cTBS treatment and not sham will result in a significant and clinical meaningful response.
Phase 3: Two post-treatment assessment moments will take place respectively 3 (max. 4) days and 10 (max. 11) days after the last treatment day. The assessments are the same clinical, cognitive and psychomotor assessments as in phase 2.
- Conditions
- Bipolar Disorder, Bipolar Depression, Bipolar I Disorder, Bipolar II Disorder, Depression, Mood Disorders
- Being tested
- cTBS, Sham cTBS
- Keywords
- bipolar depression, TMS, transcranial magnetic stimulation, add-on treatment
- Medical subject headings
- Bipolar Disorder, Depression, Mood Disorders, Mental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cTBSDevice
In the cTBS arm, the patients will receive 5 daily session cTBS (5 times uninterrupted train of 900 pulses) separated by a 15 min interval. Patients will be treated with in total 20 cTBS sessions over the right dorsolateral prefrontal cortex, spread over 4 days. A stimulation intensity of 100 % of the resting motor threshold (rMT) of the right abductor pollicis brevis muscle will be used.
Sham cTBSDevice
The sham coil has been specifically developed to mimic the real one but is not associated with a stimulus sensation compared to the coil delivering real stimulation cTBS.
| Study group | Role | What they receive |
|---|---|---|
| Active cTBS | Active comparator | Not described Receives: Device: cTBS |
| Sham cTBS | Sham comparator | Not described Receives: Device: Sham cTBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in depression severity clinician-rated
Hamilton rating scale for depression (HRSD-17); total scores ranging from 0 to 52. A higher score is indicative of greater depressive pathology
Measured: Screening, baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Secondary outcomes (14)
Changes in depression severity self-report
Beck Depression Inventory (BDI-II); total scores ranging from 0 to 63. Higher total scores indicate more severe depressive symptoms.
Measured: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Changes in suicidal thoughts - clinician-rated
Columbia-suicide severity rating scale (total score ranges from 0 to 25; a higher score represent a higher intensity of suicidality)
Measured: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Changes in cognitive symptoms (1)
Continuous performance test (CPT), a measure of a person's sustained and selective attention: d-prime (the quotient of hits/false alarms that indicate the response sensitivity for discrimination of target from nontarget stimuli). Greater scores represent better ability to distinguish and detect X and non-X stimuli (better sustained attention)
Measured: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Changes in cognitive symptoms (2)
Symbol Digit Substitution Test (SDST), examining processing speed. Differentiating between the cognitive and the psychomotor processes of slowing (matching time and writing time; msec)
Measured: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Changes in cognitive symptoms (3)
Stroop test; examining response inhibition (Stroop response interference score)
Measured: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Changes in psychomotor symptoms (1)
CORE assessment of psychomotor functioning; total score ranging from 0 to 54. A higher score is indicative of psychomotor impairment (a score of 21 or more is indicative of melancholic depression)
Measured: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Changes in psychomotor symptoms (2)
Accelometer tool (MotionWatch 8®, CamNtech, Cambridge, UK; measuring gross motor performance): total day activity level (counts per hour). Lower values indicate reduction in gross motor activity. *Cut-off levels from a control group are being collected in another research project of this research group.
Measured: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Changes in psychomotor symptoms (3)
Line-copying task (LCT): initiation and movement time (msec)
Measured: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Change in biological markers (1)
Plasma levels of C reactive protein (CRP)
Measured: Baseline and 10 days after cTBS or sham (+/- day 14)
Change in biological markers (2)
Cytokines (pg/ml)
Measured: Baseline and 10 days after cTBS or sham (+/- day 14)
Change in biological markers (3)
Kynurenines tryptophan catabolites (TRYCAT) levels (mmol/l)
Measured: Baseline and 10 days after cTBS or sham (+/- day 14)
Change in biological markers (4)
Brain-derived neurotrophic factor (BDNF; ng/ml)
Measured: Baseline and 10 days after cTBS or sham (+/- day 14)
Differences in adverse events following cTBS or sham - self report
Adverse effects questionnaire
Measured: 3 days after cTBS or sham (+/- day 7)
Differences in development of (hypo)manic symptoms
Young mania rating scale (YMRS): evaluates the presence and severity of mania. The score ranges from 0 to 60. Scores higher than 12 are indicative for mania, scores of 2 or lower indicate euthymia.
Measured: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2018
- Study start1 Aug 2018
- Primary completionJul 2020 (estimated)
- Study completionJul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universiteit Antwerpen
- Sponsor type
- University, hospital or other
- Collaborators
- Universitair Ziekenhuis Brussel
- Responsible party
- Principal investigator, Kaat Hebbrecht, Universiteit Antwerpen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03603561
- Sponsor's protocol ID
- 1808
- Status last verified
- Apr 2019
- First submitted
- 5 Jun 2018
- Last updated
- 25 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033.
PubMed 15664172
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Continuous Theta Burst Transcranial Magnetic Stimulation as an add-on Treatment for Bipolar Depression: a Multicenter Randomized Sham-controlled Trial
- ClinicalTrials.gov ID
- NCT03603561
- Acronym / sponsor ID
- 1808
- Conditions
- Bipolar Disorder, Bipolar Depression, Bipolar I Disorder, Bipolar II Disorder, Depression, Mood Disorders
- Keywords
- bipolar depression, TMS, transcranial magnetic stimulation, add-on treatment
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Universiteit AntwerpenUniversity, hospital or other
- Collaborators
- Universitair Ziekenhuis Brussel
- Study start
- 1 Aug 2018 (actual)
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Jul 2020 (estimated)
- First posted
- 27 Jul 2018 (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.
This study aims to investigate the clinical efficacy of continuous theta burst stimulation (cTBS) on the right DLPFC as an add-on treatment in bipolar depression. The study consists of three phases.
Phase 1: Bipolar depressed patients will be selected by a certified psychiatrist, who will administer (semi-)structured clinical interviews (M.I.N.I.-Plus 5.0.0, HRSD-17). The presence of exclusion criteria will be evaluated. Eligible patients will undergo MRI brain imaging for TMS neuronavigation
Phase 2: Baseline clinical, cognitive and psychomotor assessments will take place. Patients will also undergo blood samples for laboratory and research assessments.
TBS involves applying triple-pulse 50 Hz bursts given at a rate of 5 Hz uninterrupted trains (1). Patients will be treated with in total 20 continuous Theta Burst Stimulation (cTBS) session (900 pulses per session) over the right dorsolateral prefrontal cortex, which will be spread over 4 days. A stimulation intensity of 100% of the subject's resting motor threshold (rMT) of the right abductor pollicis brevis muscle will used.
Patients will be randomized to receive either the real cTBS or sham treatment. Sham stimulation will be applied with a sham coil. The sham coil produces identical sounds but is not associated with a stimulus sensation compared to the coil delivering real stimulation cTBS. The investigators expect that real cTBS treatment and not sham will result in a significant and clinical meaningful response.
Phase 3: Two post-treatment assessment moments will take place respectively 3 (max. 4) days and 10 (max. 11) days after the last treatment day. The assessments are the same clinical, cognitive and psychomotor assessments as in phase 2.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active cTBS | Active comparator | Device: cTBS |
| Sham cTBS | Sham comparator | Device: Sham cTBS |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Diagnostic and Statistical Manual-IV defined bipolar subjects (bipolar types I and II), depressed or mixed phase, confirmed by the Mini-International Neuropsychiatric Interview (MINI-plus 5.0.0.)
- Hamilton Rating Scale for Depression-17 score of 17 or more.
- Stable psychotropic medication regimen for at least 2 weeks prior to randomization and patient is willing to remain on a stable regimen from screening (S) after the second measurement point T2 (2 to 3 weeks).
- On stable antidepressant treatment for 4 weeks.
- Stable antidepressant medication but dose has been recently changed (higher/lower dose): duration of 2 weeks should lie between change of medication dose and screening (S).
Key exclusion criteria (12 listed)
- Contra-indications for TMS treatment:
- Unipolar depression
- Psychotic disorder (MINI-plus 5.0.0; DSM-IV codes 295.10, 295.20, .30, .40, .60, .70, .90, 297.10, 298.90); exceptions are: depression with psychotic features MINI-Plus 5.0.0; DSM code 296.23)
- Current alcohol dependence (MINI-plus 5.0.0. DSM IV code 303.9) (in the last year)
- Current substance abuse or dependence (DSM-IV codes 304.00-.90, 305.20 -.70) (in the last year), with the exception of nicotine and caffeine (DSM IV codes 305.10 and 305.90)
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 |
|---|---|---|
| cTBSIn the cTBS arm, the patients will receive 5 daily session cTBS (5 times uninterrupted train of 900 pulses) separated by a 15 min interval. Patients will be treated with in total 20 cTBS sessions over the right dorsolateral prefrontal cortex, spread over 4 days. A stimulation intensity of 100 % of the resting motor threshold (rMT) of the right abductor pollicis brevis muscle will be used. | Device | Active cTBS |
| Sham cTBSThe sham coil has been specifically developed to mimic the real one but is not associated with a stimulus sensation compared to the coil delivering real stimulation cTBS. | Device | Sham cTBS |
Primary outcome
Changes in depression severity clinician-rated
Time frame: Screening, baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Hamilton rating scale for depression (HRSD-17); total scores ranging from 0 to 52. A higher score is indicative of greater depressive pathology
14 secondary outcomes
Changes in depression severity self-report
Time frame: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Changes in suicidal thoughts - clinician-rated
Time frame: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Changes in cognitive symptoms (1)
Time frame: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Changes in cognitive symptoms (2)
Time frame: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Changes in cognitive symptoms (3)
Time frame: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Changes in psychomotor symptoms (1)
Time frame: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Changes in psychomotor symptoms (2)
Time frame: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Changes in psychomotor symptoms (3)
Time frame: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Change in biological markers (1)
Time frame: Baseline and 10 days after cTBS or sham (+/- day 14)
Change in biological markers (2)
Time frame: Baseline and 10 days after cTBS or sham (+/- day 14)
Change in biological markers (3)
Time frame: Baseline and 10 days after cTBS or sham (+/- day 14)
Change in biological markers (4)
Time frame: Baseline and 10 days after cTBS or sham (+/- day 14)
Differences in adverse events following cTBS or sham - self report
Time frame: 3 days after cTBS or sham (+/- day 7)
Differences in development of (hypo)manic symptoms
Time frame: Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2019.
- Background: PubMed 15664172Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033.
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing cTBS in people with Bipolar Disorder and Bipolar Depression, run by Universiteit Antwerpen at 2 sites in Belgium.
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 13 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 25 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 2 sites in Belgium. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kaat Hebbrecht, Dr (15304048 ext. +32, kaat.hebbrecht@emmaus.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in depression severity clinician-rated (time frame: Screening, baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)). 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 NCT03603561, 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 25 Apr 2019.