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

NCT03603561 | Unknown

• 1 other identifier: 1808
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

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

Keywords

bipolar depression; TMS; transcranial magnetic stimulation; add-on treatment

Outcome Measures

Primary Outcomes (1)

• 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

  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

  Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)

• Changes in suicidal thoughts - clinician-rated

  Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)

• Changes in cognitive symptoms (1)

  Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)

• Changes in cognitive symptoms (2)

  Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)

• Changes in cognitive symptoms (3)

  Baseline, 3 days after cTBS or sham (+/- day 7), 10 days after cTBS or sham (+/- day 14)

Study Arms (2)

Active cTBS

ACTIVE COMPARATOR

Device: cTBS

Sham cTBS

SHAM COMPARATOR

Device: Sham cTBS

Interventions

cTBS 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.

Active cTBS

Sham cTBS 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.

Sham cTBS

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Universiteit Antwerpen: lead
• Universitair Ziekenhuis Brussel: collaborator

Study Sites (2)

University Hospital of Brussels

Brussels, 1000, Belgium

NOT YET RECRUITING

University Psychiatric Hospital Duffel

Duffel, 2570, Belgium

RECRUITING

Related Publications (1)

• 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.

  PMID: 15664172 BACKGROUND

MeSH Terms

Conditions

Bipolar Disorder; Depression; Mood Disorders; Mental Disorders

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Behavioral Symptoms; Behavior

Central Study Contacts

Kaat Hebbrecht, Dr

CONTACT

15304048; kaat.hebbrecht@emmaus.be

Bernard Sabbe, PhD

CONTACT

15304034; bernard.sabbe@ua.ac.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 5, 2018
• First Posted: July 27, 2018
• Study Start: August 1, 2018
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: April 25, 2019

Record last verified: 2019-04

Locations

BE (2)