Continuous Theta Burst Stimulation as an add-on Treatment for Bipolar Depression

NCT ID: NCT03603561

Last Updated: 2019-04-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-01
• Study Completion Date: 2020-07-31

Brief 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.

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.

Conditions

Bipolar Disorder; Bipolar Depression; Bipolar I Disorder; Bipolar II Disorder; Depression; Mood Disorders; Mental Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Active cTBS

Group Type: ACTIVE_COMPARATOR

cTBS

Intervention Type: DEVICE

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 cTBS

Group Type: SHAM_COMPARATOR

Sham cTBS

Intervention Type: DEVICE

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.

Interventions

cTBS

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.

Intervention Type: DEVICE

Sham cTBS

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.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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).
• 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.

Exclusion Criteria

• 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.
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universitair Ziekenhuis Brussel

OTHER

Sponsor Role: collaborator

Universiteit Antwerpen

OTHER

Sponsor Role: lead

Responsible Party

Kaat Hebbrecht

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Hospital of Brussels

Brussels, , Belgium

Site Status: NOT_YET_RECRUITING

University Psychiatric Hospital Duffel

Duffel, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Kaat Hebbrecht, Dr

Role: CONTACT

kaat.hebbrecht@emmaus.be

15304048 ext. +32

Bernard Sabbe, PhD

Role: CONTACT

bernard.sabbe@ua.ac.be

15304034 ext. +32

Facility Contacts

Chris Baeken, PhD

Role: primary

chris.baeken@uzbrussel.be

9 332 43 94 ext. +32

Dieter Zeeuws, MD

Role: backup

dieter.zeeuws@uzbrussel.be

2 477 60 12 ext. +32

Kaat Hebbrecht, Dr

Role: primary

kaat.hebbrecht@emmaus.be

15304048 ext. +32

Bernard Sabbe, PhD

Role: backup

bernard.sabbe@ua.ac.be

15304034 ext. +32

References

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.

Reference Type: BACKGROUND

PMID: 15664172 (View on PubMed)

Other Identifiers

1808

Identifier Type: -

Identifier Source: org_study_id