Effects of brain stimulation on bipolar disorder symptoms and brain activity

Elucidating Neural Mechanisms of Hypo/mania Using Theta Burst Stimulation

This study is testing if a type of brain stimulation can help reduce symptoms and change brain activity in adults with bipolar disorder compared to those without it.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 134 (estimated)
• Ages: 18 Years to 35 Years
• Sex: All
• Sponsor: University of Pittsburgh (Academic / other)
• Locations: 1 site (Pittsburgh, Pennsylvania)
• Trial ID: NCT04696471 on ClinicalTrials.gov

What this trial studies

This study investigates the impact of continuous theta burst stimulation (cTBS) on brain activity and emotional responses in adults with and without Bipolar Disorder. Participants will undergo a series of brain stimulation sessions combined with functional magnetic resonance imaging (fMRI) to assess changes in brain activity while engaging in a reward-based task. The study aims to determine whether cTBS can reduce brain activity and improve symptoms in individuals with Bipolar Disorder compared to those without the condition. A sham stimulation will be included to ensure the validity of the results, with both participants and researchers blinded to the stimulation type during the sessions.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-35 with a diagnosis of Bipolar Disorder I/II in remission or with mild-moderate hypomania.

Not a fit: Patients with severe psychotic symptoms or those currently on antidepressant monotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to new non-invasive treatment options for managing symptoms of Bipolar Disorder.

How similar studies have performed: Other studies using transcranial magnetic stimulation have shown promising results in treating mood disorders, suggesting potential success for this approach.

Eligibility criteria

Inclusion Criteria:

1. All participants

   * 18-35 years of age
   * Scoring less than or equal to 8 on the Hamilton Rating Scale for Depression (HRSD) at screen visit
2. Participants with Bipolar Disorder (BD)

   * Diagnosis of Bipolar Disorder I/II (BDI/II) (DSM-5 criteria) in remission (euthymic for \>2 months) or with mild-moderate hypomania
   * \<15 on the Young Mania Rating Scale
   * Not psychotic
   * \<3 on delusions, hallucinations, unusual thought content, and conceptual disorganization items of the Positive and Negative Syndrome Scale (PANSS)
   * Unmedicated or on any combination (except antidepressant monotherapy) of anxiolytics (benzodiazepines, buspirone, pregabalin, hydroxyzine) as needed, and/or atypical antipsychotics, and/or lithium, and/or other mood stabilizers, and/or non-SNRI antidepressants and/or non benzodiazepine hypnotics taken for \>2 months, as these are commonly-prescribed medications for BD
3. Participants without Bipolar Disorder

   * No present or lifetime history of BD or psychiatric disorder other than anxiety or non BD mood disorders
   * Not in a current depressive episode
   * No family history of BD

Exclusion Criteria:

1. All participants

   * History of head injury, neurological, pervasive developmental disorder (e.g. autism), systemic medical disease and treatment (medical records, participant report)
   * Family history of epilepsy (TBS exclusion criterion)
   * Use of substances with seizure risk (e.g., stimulants) in the past month, assessed as at screening, baseline, and before each fMRI-cTBS-fMRI session
   * Mini-Mental State Examination score (cognitive state) \<24
   * Premorbid National Adult Reading Test Intelligent Quotient estimate\<85
   * Visual disturbance: \<20/40 Snellen visual acuity
   * Left/mixed handedness
   * History of alcohol/substance use disorder (SUD; all substances, including nicotine), and/or illicit substance use (except cannabis) over the last 6 months (SCID-5). Note: lifetime/present cannabis use (at non-abuse (\<3 times in the past month) and non SUD levels) will be allowed, given its common usage in BD and young adults. Cannabis SUD over the last 6 months will not be allowed. Urine tests on scan days will exclude current illicit substance use (except cannabis). Salivary alcohol tests on scan days will exclude intoxicated individuals
   * Binge drinking in the week before, and/or \>3 units/day for the 3 days before, and/or alcohol in the last 12 hrs before, any cTBS scan day, confirmed at screening and scan days (to avoid TBS during alcohol withdrawal). Alcohol/nicotine/ caffeine/cannabis use (below SCID-5 SUD, binge levels) will be allowed, and used as covariates
   * MRI exclusion criteria: metallic objects, e.g., surgical implants; claustrophobia; proneness; positive pregnancy test for females (performed at the MRRC) or self-report pregnancy
   * Inability to understand English
   * \<18 years of age or \>35 year of age

     * SNRI antidepressants and bupropion will not be allowed, as they can elevate seizure risk, a contraindication for TBS
     * Scoring greater than or equal to 8 on HRSD and in depressive episode is confirmed on SCID-5 at screen visit
     * Scoring greater than or equal to 18 on HRSD at any visit
     * In current depressive episode
2. Participants with Bipolar Disorder

   * BD diagnosis other than BDI/II
   * More severe hypo/mania (YMRS\>15)
   * Psychosis
   * Using psychotropic medications other than those allowed in inclusion criteria
3. Participants without Bipolar Disorder

   * Present/ lifetime history of any psychiatric disorder other than anxiety and non BD mood disorders
   * Family history of of BD

Where this trial is running

Pittsburgh, Pennsylvania

• University of Pittsburgh — Pittsburgh, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Mary Phillips, MD, MD — University of Pittsburgh
• Study coordinator: Simona Graur, MSW, LCSW

Conditions Bipolar Disorder; Magnetic Resonance Imaging; Transcranial Magnetic Stimulation