iTBS in Refractory Pediatric Depression

Depression Clinical Trial

Official title:

Evaluating the Efficacy and Tolerability of Targeted Transcranial Magnetic Stimulation in Youth

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03845504
• Other study ID #: 45848
• Status: Terminated
• Phase: N/A
• Start date: November 19, 2018
• Est. completion date: October 9, 2019

Study information

• Verified date: November 2023
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This work will mark the first step in understanding the neural targets for rTMS in youth with difficult to treat depressive symptoms, creating benchmarks for optimizing the safety and efficacy of rTMS for pediatric populations through precision targeting, and encourage funding applications for larger sham- controlled randomized clinical studies.

Description:

Problem Statement: Depression is a global health problem with limited novel and targeted solutions. Currently available interventions (medication and psychotherapy) have failed to provide adequate clinical improvement in 40% of adolescents with depression and only produce remission in 30% of youth. There is a clear need to develop better targeted interventions for this growing population of youth.

Specific Aims Aim 1: To examine the efficacy of a targeting strategy to optimize repetitive transcranial magnetic stimulation (rTMS) delivered to the left dorsolateral prefrontal cortex (DLPFC) to reduce depressive symptoms in adolescents between 12-17 years of age. Hypothesis 1: Six weeks of open-label daily intermittent theta-burst stimulation (iTBS) sessions delivered to the left DLPFC will be effective at reducing depressive symptoms between baseline and 10- week follow-up. Hypothesis 2: iTBS over left DLPFC will decrease functional connectivity between left DLPFC and subcallosal cingulate cortex (SCC) and will reduce depression-related hyperconnectivity between nodes of the default mode network (DMN). Hypothesis 3: Higher anti-correlation between left DLPFC and SCC and lower cingulate glutamate concentrations will predict better clinical outcome following iTBS.

Aim 2: To determine the tolerability of iTBS in adolescents between 12-17 years of age. Hypothesis 1: iTBS will be well tolerated without any more than minimal side effects. Hypothesis 2: iTBS will result in sufficient cortical excitability, as measured by 64-channel-EEG pre, during, and post iTBS, to induce an antidepressant effect but not induce seizures or other adverse events.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: October 9, 2019
• Est. primary completion date: October 9, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 21 Years

Eligibility

Inclusion Criteria:

• 10 participants ages 12-21 years of age

• with at least moderate to severe depressive symptoms confirmed by the Children's Depression Rating Scale-Revised (CDRS-R>40) or Hamilton Rating Scale for Depression (HRSD-17 = 18)

• able to commit to protocol schedule and provide Informed consent by a legal guardian and assent by a youth participant

• have had at least one prior antidepressant treatment failure with adequate dose and duration

Exclusion Criteria:

• prior neurological diagnosis (neurodevelopmental disorders, strokes/traumatic brain injuries, brain tumor, epilepsy)

• contraindications for TMS or MRI e.g. have any implanted metal

• unstable medical conditions

• acute suicide risk, defined as an attempt in past 6 months that required medical treatment, or history of =2 suicide attempts in the past 12 months, or has a clear cut plan for suicide

• pregnancy, suspected pregnancy or not on birth control if sexually active; 6) Inability to locate and quantify a motor threshold

• any factor that the PI determines to be reason for exclusion.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder

Intervention

Device:
• Intermittent Theta Burst Stimulation
Stimulation will be administered using the MagVenture MagPro rTMS Research System at currently FDA approved parameters (www.magvitatms.com). The TBS parameters will be 3-pulse 50-Hz bursts given every 200 ms (at 5 Hz) and an intensity of 80% active motor threshold, as measured from the right first dorsal interosseous muscle by a hand-held 700-mm figure-of-eight coil. rTMS will be applied for 9 min delivering a total of 1800 pulses/session.

Locations

Country	Name	City	State
United States	Stanford University Pediatric Mood Disorders Program	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

References & Publications (5)

Blumberger DM, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, Knyahnytska Y, Kennedy SH, Lam RW, Daskalakis ZJ, Downar J. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Lancet. 2018 Apr 28;391(10131):1683-1692. doi: 10.1016/S0140-6736(18)30295-2. Epub 2018 Apr 26. Erratum In: Lancet. 2018 Jun 23;391(10139):e24. — View Citation

Li CT, Chen MH, Juan CH, Liu RS, Lin WC, Bai YM, Su TP. Effects of prefrontal theta-burst stimulation on brain function in treatment-resistant depression: A randomized sham-controlled neuroimaging study. Brain Stimul. 2018 Sep-Oct;11(5):1054-1062. doi: 10.1016/j.brs.2018.04.014. Epub 2018 Apr 23. — View Citation

Oberman LM, Pascual-Leone A, Rotenberg A. Modulation of corticospinal excitability by transcranial magnetic stimulation in children and adolescents with autism spectrum disorder. Front Hum Neurosci. 2014 Aug 13;8:627. doi: 10.3389/fnhum.2014.00627. eCollection 2014. — View Citation

Wall CA, Croarkin PE, Maroney-Smith MJ, Haugen LM, Baruth JM, Frye MA, Sampson SM, Port JD. Magnetic Resonance Imaging-Guided, Open-Label, High-Frequency Repetitive Transcranial Magnetic Stimulation for Adolescents with Major Depressive Disorder. J Child Adolesc Psychopharmacol. 2016 Sep;26(7):582-9. doi: 10.1089/cap.2015.0217. Epub 2016 Feb 5. — View Citation

Weigand A, Horn A, Caballero R, Cooke D, Stern AP, Taylor SF, Press D, Pascual-Leone A, Fox MD. Prospective Validation That Subgenual Connectivity Predicts Antidepressant Efficacy of Transcranial Magnetic Stimulation Sites. Biol Psychiatry. 2018 Jul 1;84(1):28-37. doi: 10.1016/j.biopsych.2017.10.028. Epub 2017 Nov 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Children's Depression Rating Scale - Revised (CDRS-R) Score From	Standardized assessment to determine depression severity. The CDRS-R total score is the sum of the responses to 17 questions. Each question is graded on a 5- or 7-point scale. Total score ranges from 17-113. In general, higher values of CDRS-R total score represent greater severity of illness. Response to treatment is determined by a = 50% reduction in score from baseline to end of treatment.	Baseline and week 6
Secondary	Change in Hamilton Depression Rating Scale (HDRS-17)	Standardized assessment to determine depression severity. HDRS-17, a clinician-rated measure of depressive symptoms that consists of 17 items rated using a semi-structured interview. Eight of the 17 HDRS-17 items are rated on a 5-point scale (0=absent; 1=doubtful or mild; 2=mild to moderate; 3=moderate to severe; 4=very severe), while the remaining 9 items are rated on a 3-point scale (0=absent; 1=doubtful or mild; 2=clearly present), yielding a minimum total score of 0 (least severe) and a maximum score of 52 (most severe). Response to treatment is determined by a = 50% reduction in score from baseline to end of treatment.	Baseline and week 6