Accelerated Bilateral Sequential Theta Burst Stimulation in Older Adults With Treatment-resistant Depression (CogniTReaD)

March 14, 2024 updated by: Ontario Shores Centre for Mental Health Sciences

Effects of Accelerated Bilateral Sequential Theta Burst Stimulation on Dual-task Cost, Depression, Cognition and Other Outcomes in Older Adults With Treatment-resistant Depression: A Randomized, Double-blind, Sham-controlled Trial

The CogniTReaD study is a pilot clinical trial that will compare the effects of active accelerated bilateral sequential theta burst stimulation (absTBS) and sham or inactive treatment. The goal is to see if absTBS can help older adults with treatment-resistant depression (TRD) by looking at dual-task cost and mood, as well as other cognitive functions, anxiety levels, quality of life, and physical performance, while also checking for any treatment side effects. The study will recruit participants who will receive different study treatments in a specific order. The study will be double-blinded, meaning neither the participants nor the researchers will know who is receiving which treatment. The study will include people who are 50 years old or older and diagnosed with treatment-resistant depression with at least a moderate severity of depression. This study seeks to discover if absTBS can modify a dementia risk marker (i.e., dual-task cost and depression) in older patients with TRD, and to determine the effect size for larger investigations in the future.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The CogniTReaD study is a two-arm, sham-controlled, double-blinded, treatment-sequenced, randomized clinical trial that will evaluate and explore the effects and safety of accelerated bilateral sequential theta burst stimulation (absTBS) compared to sham control in terms of improving dual-task cost, cognitive functions, depression, other outcomes (anxiety, health-related quality of life, activities of daily living, global impression, and other gait performance), and occurrence of adverse events (AE) measured at Week 2 (i.e., posttreatment acute effects) in older adults with treatment-resistant depression (TRD). We shall also evaluate the effects and safety of absTBS on improving dual-task cost, cognitive functions, depression and occurrence of AE in terms of AE occurrences measured at Week 6, Week 8, and Week 10 (i.e., posttreatment delayed effects) in older adults with TRD.

Study Type

Interventional

Enrollment (Estimated)

54

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, L1N 5S9
        • Recruiting
        • Ontario Shores Centre for Mental Health Sciences
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  1. Aged 50 years or older;
  2. Mini International Neuropsychiatric Interview (MINI)-confirmed diagnosis of a non-psychotic major depressive disorder;
  3. Currently in a major depressive episode with a score on HAMD-17 of 17 or more;
  4. Insufficient response (i.e., failure to achieve remission) to at least two appropriate courses of antidepressant medications during the current depressive episode (i.e., meeting the criteria for TRD);
  5. Participants taking or not taking any psychotropic medication/s. If the eligible participant is on any psychotropic medications, the participant should have taken the medication/s at a stable dose for at least 1 week before the start of study intervention treatment and be willing to remain on a stable dose throughout the study follow-up;
  6. Passing the TMS safety screen; and
  7. Those who have the capacity to provide consent and who voluntary consent to participate in the study.

Exclusion Criteria

  1. Those with MINI-confirmed active substance use disorder within the last 3 months;
  2. Those with lifetime MINI-confirmed diagnosis of bipolar I disorder, delusional disorder, schizophrenia, schizoaffective disorder, or schizophreniform disorder;
  3. Those with major unstable medical comorbidities (i.e., rapidly deteriorating medical/neurological conditions that poses a significant risk to a person's life);
  4. Those with a diagnosis of dementia confirmed using the Global Clinical Dementia Rating (CDR) with a score greater than or equal to 1.
  5. Those with significant neurological conditions, such as those with any disease process associated with increased intracranial pressure, space-occupying intracranial lesion, history of epilepsy/seizure except those induced by ECT, or febrile seizure of infancy or a single occurrence of seizure associated with a known drug, cerebral aneurysm, or major head trauma resulting to loss of consciousness more than 5 minutes;
  6. Those with cardiac pacemaker or implanted mediation pump;
  7. Those with intracranial implants/hardwares, including but not limited to aneurysm clips, shunts, stimulators, cochlear implants, electrodes, or any other metal material inside or near the head (excluding the mouth) that cannot be safely removed;
  8. Those who are taking more than 2 mg of Lorazepam daily (or equivalent) or taking any dose of an anticonvulsant that may potentially hamper rTMS efficacy;
  9. Those who are unable to express and understand using the English language; and
  10. Individuals who are pregnant or who are likely pregnant.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: absTBS-sham treatment sequence arm
Those assigned to the accelerated bilateral sequential theta burst stimulation (absTBS)-sham arm shall receive the blinded active absTBS treatment at Week 1. At Week 3, they shall receive the blinded sham treatment.
Device: active accelerated bilateral sequential theta burst stimulation and sham treatment

We shall use the Magpro device (Magventure) employing the specialized Active/Sham B70 coil.

absTBS shall be administered consisting of 6 sessions daily (with a 50-minute interval between treatment sessions) on Mondays to Fridays or for a maximum of 5 working days of daily treatment. The target stimulation intensity will be set at 90 to 120% of the subject's resting motor threshold (RMT). Each session shall be composed of administration of continuous theta burst stimulation (triplet burst pulses at 50 Hz, repeated at 5 Hz, for a total of 600 pulses per session over 40 seconds administered on the right dorsolateral prefrontal cortex) and then intermittent theta burst stimulation (triplet burst pulses at 50 Hz bursts, repeated at 5 Hz, 2 s on and 8 s off, for a total of 600 pulses per session over about 3 min, administered on the left dorsolateral prefrontal cortex).

The sham treatment will be conducted for the same number of sessions and duration as the absTBS treatment sessions.
Other: Sham-absTBS treatment sequence arm
In the sham-absTBS arm, the blinded sham treatment shall be administered at Week 1. The blinded active absTBS treatment shall be given at Week 3.
Device: active accelerated bilateral sequential theta burst stimulation and sham treatment

We shall use the Magpro device (Magventure) employing the specialized Active/Sham B70 coil.

absTBS shall be administered consisting of 6 sessions daily (with a 50-minute interval between treatment sessions) on Mondays to Fridays or for a maximum of 5 working days of daily treatment. The target stimulation intensity will be set at 90 to 120% of the subject's resting motor threshold (RMT). Each session shall be composed of administration of continuous theta burst stimulation (triplet burst pulses at 50 Hz, repeated at 5 Hz, for a total of 600 pulses per session over 40 seconds administered on the right dorsolateral prefrontal cortex) and then intermittent theta burst stimulation (triplet burst pulses at 50 Hz bursts, repeated at 5 Hz, 2 s on and 8 s off, for a total of 600 pulses per session over about 3 min, administered on the left dorsolateral prefrontal cortex).

The sham treatment will be conducted for the same number of sessions and duration as the absTBS treatment sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Dual-task Cost
Time Frame: Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Change in Hamilton Depression Rating Scale 17 (HAMD-17) score
Time Frame: Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Adverse events (AE)
Time Frame: Week 1, Week 2, Week 3, Week 6, Week 8, and Week 10

An AE is defined as any untoward medical occurrence associated with any of the study interventions (active absTBS or sham) whether or not considered related to the study intervention.

A serious AE to any serious and unforeseen occurrence related or possibly related to the participation in the study that can lead to hospitalization, disability, or death.
Week 1, Week 2, Week 3, Week 6, Week 8, and Week 10

Secondary Outcome Measures

Outcome Measure
Time Frame
Change in Alzheimer's Disease Assessment Scale-Cognitive-13 (ADAS-Cog-13) score
Time Frame: Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Change in Alzheimer's Disease Assessment Scale-Cognitive-13 (ADAS-Cog-13) plus modalities score
Time Frame: Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Change in Trail Making A (TMT-A) score
Time Frame: Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Change in Trail Making B (TMT-B) score
Time Frame: Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Change in Digit Symbol Substitution Test (DSST) score
Time Frame: Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Change in Digit Span Forward (DSF) score
Time Frame: Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Change in Digit Span Backward (DSB) score
Time Frame: Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Change in Category Verbal Fluency (CVF) score
Time Frame: Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Change in Montreal Cognitive Assessment (MoCA) score
Time Frame: Week 0 (baseline), Week 2
Week 0 (baseline), Week 2
Change in Colour Word Interference Test (CWIT) score
Time Frame: Week 0 (baseline), Week 2
Week 0 (baseline), Week 2
Change in Patient Health Questionnaire-9 (PHQ-9) score
Time Frame: Week 0 (baseline), Week 2
Week 0 (baseline), Week 2
Change in Geriatric Depression Scale 30 (GDS-30) score
Time Frame: Week 0 (baseline), Week 2
Week 0 (baseline), Week 2
Change in Generalized Anxiety Disorder 7 (GAD-7) score
Time Frame: Week 0 (baseline), Week 2
Week 0 (baseline), Week 2
Change in Short Form 36 (SF-36) score
Time Frame: Week 0 (baseline), Week 2
Week 0 (baseline), Week 2
Change in Alzheimer Disease Cooperative Study - Activities of Daily Living inventory (ADCS-ADL) score
Time Frame: Week 0 (baseline), Week 2
Week 0 (baseline), Week 2
Change in Lawton-Brody Instrumental Activities of Daily Living (LB-IADL) score
Time Frame: Week 0 (baseline), Week 2
Week 0 (baseline), Week 2
Change in Clinical Global Impression (CGI) score
Time Frame: Week 0 (baseline), Week 2
Week 0 (baseline), Week 2
Change in Short Physical Performance Battery (SPPB) score
Time Frame: Week 0 (baseline), Week 2
Week 0 (baseline), Week 2
Change in Timed Up & Go (TUG) score
Time Frame: Week 0 (baseline), Week 2
Week 0 (baseline), Week 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ontario Shores Centre for Mental Health Sciences

Collaborators

Sunnybrook Health Sciences Centre

Investigators

  • Principal Investigator: Amer M. Burhan, MBChB, MSc, Ontario Shores Centre for Mental Health Sciences and University of Toronto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2024

Primary Completion (Estimated)

March 30, 2026

Study Completion (Estimated)

March 30, 2026

Study Registration Dates

First Submitted

March 14, 2024

First Submitted That Met QC Criteria

March 14, 2024

First Posted (Actual)

March 21, 2024

Study Record Updates

Last Update Posted (Actual)

March 21, 2024

Last Update Submitted That Met QC Criteria

March 14, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23-015-B

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Anonymized individual participant data can be made available by request from qualified researchers/investigators.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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