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A Novel 4-day Linear Asymmetric rTMS for Adolescents With Treatment-Resistant Depression

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ClinicalTrials.gov Identifier: NCT03986658
Recruitment Status : Not yet recruiting
First Posted : June 14, 2019
Last Update Posted : August 15, 2019
Sponsor:
Collaborator:
Children's Hospital of Eastern Ontario
Information provided by (Responsible Party):
NeuroQore Inc.

Brief Summary:
In this observational pilot study, all patients with Treatment-Resistant Depression will receive the NeuroQore First Dawn rTMS intervention. This study will investigate the feasibility, safety and experiences of the procedures to inform a large-scale Randomized Control Trial (RCT).

Condition or disease Intervention/treatment
Treatment Resistant Depression Device: NeuroQore First Dawn rTMS System

Detailed Description:

Major Depressive Disorder (MDD) is characterized by at least one basic symptom occurring nearly every day for at least two weeks, for most of each day and an additional minimum of three symptoms that also are present nearly every day for at least two weeks. The common symptoms are sadness or ahedonia, i.e., a loss of pleasure in daily life. The additional required symptoms may be a change in weight (either gain or loss, without planning to do so), inability to sleep or increased sleep beyond the person's normal patterns, physical agitation or marked slowness in movement, loss of energy or fatigue, feelings of worthlessness or excessive guilt, inability to concentrate or make decisions, recurrent thoughts of death or thoughts of suicide. The symptom must cause dysfunction and must be different than the person's normal baseline level of function. Although MDD was initially thought to be an adult disorder, it has now been well described in adolescents.

MDD criteria for diagnosing adults is the same for adolescents, however, young people may present a bit differently in that they may be more irritable rather than being consistently sad. The lifetime prevalence of MDD in adolescents is 11% and recent data indicate that the 12-month prevalence increased from 8.7% in 2011 to 11% in 2014. If untreated, MDD can derail normal development, become chronic, and result in suicide. MDD is also associated with poor lifetime outcomes, such as, reoccurrence of MDD, higher rates of suicide, development of substance use disorders, and difficulties in social, work and physical health domains. Effective treatment consisting of a serotonin re-uptake inhibitor (SSRI) medication and/or cognitive behavioural therapy (CBT) or interpersonal psychotherapy (IPT), administered as early as possible, is optimal. Unfortunately, treating adolescent MDD is not easy. Although much progress has been made, 30-40% of adolescents will not respond to the gold standard of care.

Clinical researchers define treatment-resistant adolescent MDD as having failed adequate trials of an antidepressant medication, CBT or both. Those who do not respond have higher rates of suicide, poorer school achievement, and increased substance abuse disorders. Current recommendations for these individuals involve changing medications, adding medications of different categories, and adding CBT or IPT if not previously done. However, the success rate with these additional treatments can still leave 40% of youth non-responsive to one line of treatment also non-responsive to additional pharmacological/psychotherapeutic interventions. Several non-pharmacologic interventions have been used in adults, such as electroconvulsive therapy (ECT), vagus nerve stimulation, and repetitive transcranial magnetic stimulation (rTMS). Extreme approaches like ECT are only approved for adolescents when someone has not responded to multiple medication trials, failed at least one psychotherapy, or has severe MDD or bipolar disorder with psychosis.

rTMS is a promising intervention for adults and adolescents with major depressive disorder. Conventional rTMS has been limited to sine biphasic electromagnetic pulses with underwhelming clinical outcomes. NeuroQore has developed the First Dawn rTMS system, world's first and only rTMS system that can sustain a new form of electromagnetic pulse for therapeutic application. Safety and pilot studies with First Dawn have been conducted on healthy volunteers (N = 12) and adult patients with TRD (N = 20). Please see https://clinicaltrials.gov/ct2/show/NCT02667041 for more details on this completed pilot study.


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Study Type : Observational
Estimated Enrollment : 5 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: NeuroQore First Dawn rTMS System for Adolescent Treatment-Resistant Depression: Feasibility, Side Effects, and Patient Experience
Estimated Study Start Date : November 2019
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Repetitive Transcranial Magnetic Stimulation (rTMS)
NeuroQore First Dawn rTMS System
Device: NeuroQore First Dawn rTMS System
All participants will receive left dorsolateral prefrontal cortex rTMS.




Primary Outcome Measures :
  1. Patient Completion Rate [ Time Frame: 101 Days ]
    Number of patients who complete the study divided by the number of patients who enrol in the study.

  2. Patient Enrollment Rate [ Time Frame: Day 1 ]
    Number of patients who enroll divided by the number of patients who are approached about the study.


Secondary Outcome Measures :
  1. Changes in self-reported MDD symptoms. Measured with the Child Depression Inventory-2 (CDI-2). [ Time Frame: Day 1, 4 days, 7 days and 101 days. ]
    The Child Depression Inventory-2 takes 20 minutes to administer and is the most extensively used self-rated depression scale for children. The 27 items on the assessment are grouped into five major factor areas and is for children and youth up to the age of 17 years. Young people rate themselves based on how they feel and think, with each statement being rated from 0 to 2, with a range of scores from 0-54. A score of >20 is indicative of depression. Higher scores indicate increased depression. This scale has no sub-scales.

  2. Changes in clinician rated MDD symptoms. Measured with the Child Depression Rating Scale- Revised (CDRS-R) [ Time Frame: Day 1, 4 days, 7 days and 101 days. ]
    The Child Depression Rating Scale-Revised has 17 items, is for 6-18 year-olds, and takes 20-30 minutes to administer. This scale has items ranging from 1 to 5 or 1 to 7 (possible total score from 17 to 113) and is rated by a clinician. It is the most widely used rating scale for assessing severity of depression and changes in depressive symptoms for clinical research trials. A score of >40 is indicative of depression, whereas a score of <28 is used to define remission. Higher scores represent increased depression. There are no sub-scales for this measure.

  3. Children's Global Assessment Scale (C-GAS) [ Time Frame: Day 1, 4 days, 7 days and 101 days. ]
    This scale is the most widely used measure of social and psychiatric functioning for children aged 4-17 years. The Children's Global Assessment Scale is a single rating scale with a range of scores from 1 to 100, rated by the interviewer, synthesizing all sources of information at the end of intake. Higher scores indicate better function (12). It takes 1 minute to administer and assesses the adolescent's functioning within the past month of their life. We will adapt it to days or weeks, as below. This measure has no sub-scales.

  4. Side Effects Profile. Measured with the rTMS Side Effect Questionnaire. [ Time Frame: Day 1, after each of the four days of treatment, 11 days, 101 days. ]
    This questionnaire is a Likert rating scale scored set of items about headache, neck pain, hearing changes, impaired cognition, trouble concentrating, acute mood changes, and other general symptoms. It will assess the side effects severity, relationship to intervention and additional notes for clinician. The severity ratings will range from 1 (Absent) to 4 (Severe). Relationship to the rTMS ratings will range from 1 (None) to 5 (Definitive).

  5. Changes in mental status. Measured with the Mini-Mental State Examination (MMSE). [ Time Frame: Day 1, Days 2, 3, 4, 5, 11 days, 101 days. ]
    The Mini-Mental State Examination examines functions including registration (repeating named prompts), attention and calculation, recall, language, ability to follow simple commands and orientation. It takes 5-10 minutes to administer and each task has a score with a maximum of 30 points total. A score of 24 or higher purports to identify individuals who are cognitively intact. Higher scores indicate better mental function. This measure has no sub-scales.

  6. Changes in short-term verbal memory. Measured with the Hopkins Verbal Learning Test- Revised (HLVT-R). [ Time Frame: Day 1, Day 4, 11 days, 101 days. ]
    The Hopkins Verbal Learning Test- Revised takes 15 minutes to administer and is a brief verbal learning and memory test with six alternative forms. Each form contains 12 nouns, four words each from one of three semantic categories, to be learned over the course of the three learning tasks. Correct responses across these 3 learning trials are summed for the Total Recall score (range 0-36). After a 20-25 minute delay, free recall of the words is again attempted. The Delayed Recall score is the correct responses on that trial (range 0-12). Two more scores are calculated: Retention and Recognition Discrimination index. Retention is calculated as (Delayed Recall/higher score Trials 2 or 3) x 100. Recognition is calculated as the number of hits - number of false positives. For all scores, higher values indicate better performance, except false positive errors, which is the opposite.

  7. Participant experience. Measured with the Multi-Care Institute for Research and Innovation Research Participant Satisfaction Questionnaire [ Time Frame: 101 days ]
    We will adapt the Multi-Care Institute for Research and Innovation Research Participant Satisfaction Questionnaire for adolescents. The questionnaire includes 7 questions related to the study, 27 questions on a 5-point Likert scale (Strongly Agree, Agree, Neutral, Disagree, Strongly Disagree), two ranking questions, three free-text responses options, four demographic questions for a total of 45 questions. This measure was developed to assess the experience of participants in clinical trials. Likert scale questions will be evaluated with a "top box" score (the percentage of respondents who selected strongly agree for each question) and a Six Sigma percentile rank procedure. Free recall questions will be reviewed from a quality improvement perspective and to receive feedback for future trials.



Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Adolescent inpatients with Treatment-Resistant Depression
Criteria

Inclusion Criteria:

  • Age 15-17.99
  • Biologically male or female
  • Meet criteria for Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) Major Depressive Disorder
  • Meet criteria for current treatment resistant depression: failure of one adequate trial of an antidepressant medication
  • Have a score of >40 on the Child Depression Rating Scale- Revised (CDRS-R)
  • Have a score of >20 on the Child Depression Inventory (CDI-2)
  • Patients who select English as a preferred language to receive services

Exclusion Criteria:

  • Positive pregnancy test
  • Currently have one of the following DSM-5 disorders: Bipolar Disorder, Schizophrenia, Autism Spectrum Disorder, Intellectual Disability, Substance Abuse Disorder
  • Are using any medication that would lower seizure threshold or affect brain function
  • Are on psychotropic medication and have had a change in medication in the last 2 weeks
  • Fail the TMS safety screening questionnaire
  • Fail the Functional Magnetic Resonance Imaging (fMRI) screening process
  • Are left handed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03986658


Contacts
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Contact: Kathleen Pajer, MD 613-737-7600 ext 2723 kpajer@cheo.on.ca
Contact: Scott Taylor, BA 613-737-7600 ext 4136 staylor@cheo.on.ca

Locations
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Canada, Ontario
Children's Hospital of Eastern Ontario Not yet recruiting
Ottawa, Ontario, Canada, K1H 8L1
Contact: Kathleen Pajer, MD    613-737-7600 ext 2723    kpajer@cheo.on.ca   
Sub-Investigator: Robert Chen, MD, Toronto Western Hospital, University of Toronto         
Sub-Investigator: Paula Cloutier, MA         
Sub-Investigator: Addo Boafo, MD         
Sub-Investigator: Elka Miller, MD         
Sponsors and Collaborators
NeuroQore Inc.
Children's Hospital of Eastern Ontario
Investigators
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Principal Investigator: Kathleen Pajer, MD Children's Hospital of Eastern Ontario (CHEO)

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Responsible Party: NeuroQore Inc.
ClinicalTrials.gov Identifier: NCT03986658     History of Changes
Other Study ID Numbers: CHEO19P1
First Posted: June 14, 2019    Key Record Dates
Last Update Posted: August 15, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: clintrials.gov

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by NeuroQore Inc.:
Major Depressive Disorder
Repetitive Transcranial Magnetic Stimulation (rTMS)
Treatment-Resistant Depression
Adolescents

Additional relevant MeSH terms:
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Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders