Clinical trial NCT03986658: Linear Asymmetric rTMS in Adolescent Treatment-Resistant Depression: Tolerability of Treatment Durations Ranging From Ten Days to One Day
Official title: Dose-Response Study of Linear Asymmetric rTMS in Adolescent Treatment-Resistant Depression: Tolerability of Treatment Durations Ranging From Ten Days to One Day
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Treatment Resistant Depression
Keywords: Major Depressive Disorder
Repetitive Transcranial Magnetic Stimulation (rTMS)
Treatment-Resistant Depression
Adolescents
Lead sponsor: NeuroQore Inc.
Sponsor class: INDUSTRY
Collaborators: name: Children's Hospital of Eastern Ontario
First posted: 2019-06-14
Enrollment: 19
Sex: ALL
Minimum age (years): 15
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: rTMS
Primary purpose: TREATMENT

Brief summary: This is a pilot interventional study to investigate the acceptability, tolerability, and side effect profile for varying numbers of treatment sessions/day of a new rTMS treatment in adolescents with treatment-resistant depression (TRD). Conventional rTMS has been limited to sinusoidal biphasic electromagnetic pulses. In contrast, the First Dawn rTMS system by NeuroQore can sustain a repetitive linear asymmetric pulse. In addition, identification of rTMS treatment sites in adolescents with TRD most often relies on anatomic landmarks, but the First Dawn rTMS system utilizes personal fMRI data in a novel algorithm to determine where to apply the rTMS in each patient.

Based on adult data in healthy volunteers and patients with TRD, the investigators propose that the First Dawn rTMS system will be acceptable and well-tolerated by adolescents and will have minimal side effects. Please see https://clinicaltrials.gov/ct2/show/NCT02667041 for details on the completed pilot study in adults.

The investigators aim to investigate acceptability, tolerability, and side effects in groups of patients receiving treatment in numbers of sessions/day that are gradually accelerated over the course of the study. Results will be used to inform the development of a randomized controlled trial.

Detailed description: The 18 patients will be placed into 6 sub-groups sequentially as they are enrolled. All patients will receive a maximum of 30,000 pulses in their treatment course, as tolerated. The first group will receive daily sessions, similar to standard rTMS treatment. Each of the remaining groups will be set to receive more frequent sessions/day in decreasing numbers of days on a graduated schedule while holding the total number of pulses for each patient's treatment course at 30,000 pulses. in addition, the investigators will recruit one healthy volunteer to test fMRI server data transfer and analysis. This healthy volunteer will not receive rTMS.

Primary Objectives

The primary objectives of this study are to assess: 1) the feasibility of enrollment (number of patients who enroll divided by the number of patients approached), 2) study retention (number of patients completing the study divided by the number enrolled), and 3) AE/SE profile of the treatment at each protocol level and 4) patient experience in the study across the sample and within the sub-groups.

Secondary Objectives

The secondary objectives of this study are to: 1) evaluate daily changes in symptoms of depression and mental status; 2) evaluate fMRI changes in the LDLPFC after treatment; 3) evaluate post-treatment and 3-month changes in depression symptoms, global function, mental status, verbal memory.

Eligibility criteria: Inclusion:

1. Meets criteria for DSM-5 MDD, as determined by a structured psychiatric interview.
2. Meets criteria for TRD:

   1. failed two adequate courses of antidepressant medication OR
   2. failed adequate course of medication AND one course of psychotherapy.
3. Score of \> 40 on Child Depression Rating Scale-Revised OR score of \> 20 on Child Depression Inventory-2.
4. Fluent in speaking and reading English.

Exclusion:

1. Positive pregnancy test.
2. Current or past: bipolar disorder, psychotic disorder, autism spectrum disorder, intellectual disability, substance use disorder, conduct disorder, as determined by a structured psychiatric interview.
3. Medical illness that could lower the seizure threshold, e.g., epilepsy from any cause.
4. Medications that could lower the seizure threshold or affect brain function.
5. Psychotropic medications changed in two weeks prior to enrollment.
6. Fails the TMS safety screening questionnaire.
7. Fails fMRI screening process.
8. Left-handed (may indicate different cortical lateralization which could affect outcomes).
9. Involuntarily committed to the hospital.

Primary outcomes:
measure: Patient Enrollment Rate
timeFrame: Through study completion, an average of 10 months
measure: Patient Completion Rate
timeFrame: Through study completion, an average of 10 months
measure: Side Effects Profile
timeFrame: Through study completion, an average of 10 months
measure: Patient Experience
timeFrame: Through study completion, an average of 10 months
Secondary outcomes:
measure: Change in self-reported MDD symptoms
timeFrame: Change from baseline score to score at 3 months
measure: Change in clinician-rated MDD symptoms
timeFrame: Change from baseline score to score at 3 months
measure: Change in function
timeFrame: Change from baseline score to score at 3 months
measure: Change in mental status
timeFrame: Change from baseline score to score at 3 months
measure: Change in short-term verbal memory
timeFrame: Change from baseline score to score at 3 months
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
Study officials:
affiliation: Children's Hospital of Eastern Ontario (CHEO)
name: Kathleen Pajer, MD
role: PRINCIPAL_INVESTIGATOR
References: