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

Depressive Disorder, Treatment-Resistant Clinical Trial

— CogniTReaD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06323486
• Other study ID #: 23-015-B
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2024
• Est. completion date: March 30, 2026

Study information

• Verified date: March 2024
• Source: Ontario Shores Centre for Mental Health Sciences
• Contact: Amer M. Burhan, MBChB, MSc
• Phone: 905.430.4055
• Email: burhana[@]ontarioshores.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: March 30, 2026
• Est. primary completion date: March 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant

Intervention

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.

Locations

Country	Name	City	State
Canada	Ontario Shores Centre for Mental Health Sciences	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Ontario Shores Centre for Mental Health Sciences	Sunnybrook Health Sciences Centre

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Dual-task Cost		Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Primary	Change in Hamilton Depression Rating Scale 17 (HAMD-17) score		Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Primary	Adverse events (AE)	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	Change in Alzheimer's Disease Assessment Scale-Cognitive-13 (ADAS-Cog-13) score		Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Secondary	Change in Alzheimer's Disease Assessment Scale-Cognitive-13 (ADAS-Cog-13) plus modalities score		Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Secondary	Change in Trail Making A (TMT-A) score		Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Secondary	Change in Trail Making B (TMT-B) score		Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Secondary	Change in Digit Symbol Substitution Test (DSST) score		Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Secondary	Change in Digit Span Forward (DSF) score		Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Secondary	Change in Digit Span Backward (DSB) score		Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Secondary	Change in Category Verbal Fluency (CVF) score		Week 0 (baseline), Week 2, Week 6, Week 8, and Week 10
Secondary	Change in Montreal Cognitive Assessment (MoCA) score		Week 0 (baseline), Week 2
Secondary	Change in Colour Word Interference Test (CWIT) score		Week 0 (baseline), Week 2
Secondary	Change in Patient Health Questionnaire-9 (PHQ-9) score		Week 0 (baseline), Week 2
Secondary	Change in Geriatric Depression Scale 30 (GDS-30) score		Week 0 (baseline), Week 2
Secondary	Change in Generalized Anxiety Disorder 7 (GAD-7) score		Week 0 (baseline), Week 2
Secondary	Change in Short Form 36 (SF-36) score		Week 0 (baseline), Week 2
Secondary	Change in Alzheimer Disease Cooperative Study - Activities of Daily Living inventory (ADCS-ADL) score		Week 0 (baseline), Week 2
Secondary	Change in Lawton-Brody Instrumental Activities of Daily Living (LB-IADL) score		Week 0 (baseline), Week 2
Secondary	Change in Clinical Global Impression (CGI) score		Week 0 (baseline), Week 2
Secondary	Change in Short Physical Performance Battery (SPPB) score		Week 0 (baseline), Week 2
Secondary	Change in Timed Up & Go (TUG) score		Week 0 (baseline), Week 2