Depression Mental and Behavioural Disorders
Conditions
Interventions
Current interventions as of 13/10/2021:
The study is a multicentre parallel-group, double-blinded randomised controlled trial of the efficacy of Connectivity Guided Intermittent theta-burst stimulatio
in patients over the age of 18 who have a diagnosis of moderate to severe major depressive disorder and have treatment-resistant depression. The study will look to recruit 266 patients (133 in each tr
after 1/9/20 with restart following a break in recruitment with the COVID-19 pandemic the following sites reopened to recruitment
Nottingham, London, Newcastle and Oldham with a revision to recruitment rates and use of remote methods when possible. Recruitment will be from both primary and secondary care settings by a letter of
Sponsors
Nottinghamshire Healthcare NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 13/10/2021: 1. Adults >18 years 2. Diagnosis of MDD (defined according to DSM-5) that is treatment resistant (defined as scoring 2 or more (42) on the Massachusetts General Hospital Treatment Resistant Depression staging score (51) See appendix on more detailed scoring of treatment resistance 3. HDRS-17 score of 16 or more (moderate to severe depression) (52) 4. Capacity to provide informed consent before any trial-related activities Previous inclusion criteria: 1. Adults >18 years 2. Diagnosis of MDD (defined according to DSM-5) that is treatment resistant (defined as scoring 2 or more on the Massachusetts General Hospital Treatment Resistant Depression staging score) 3. Capacity to provide informed consent before any trial-related activities
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 02/07/2019: History of bipolar disorder (due to risk of mania) or depression secondary to other mental disorder 2. Neurological conditions e.g. brain neoplasm, cerebrovascular events, epilepsy, neurodegenerative disorders, and prior brain surgery 3. Standard contraindications to MRI i.e. irremovable metal objects in and around body e.g. cardiac pacemaker, implanted medication pump and pregnancy (any doubt resolved by pregnancy test, women of childbearing age taking precautions against pregnancy) This will include other potential complicated factors such as red tattoo’s which consist of iron on the head, neck and back and claustrophobia (we offer mock scanner testing and training in some sites) 4. Major unstable medical illness requiring further investigation or treatment. 5. Change in prescribed medication 2 weeks before baseline assessment. 6. Prescription of lamotrigine, gabapentin, pregabalin in the 2 weeks prior to baseline assessment. 7. Daily prescription of benzodiazepine above 5 mg diazepam equivalents, zopiclone above 7.5 mg, zolpidem above 10 mg or zaleplon above 10 mg. These drugs should not be used intermittently in the 2 weeks before baseline assessment. 8. Current substance abuse or dependence defined by DSM-5 criteria) 9. Prior TMS treatment. 10. At risk of suicidality. 11. Potential complicated factors relating to the TMS treatment i.e. hairstyles which would impair magnetic transmission and piercings. (Participants would only be excluded if they chose to not make the changes required to ensure effective treatment.) 12. Involved with any other clinical trial at the time of consent or 6 months prior. 13. Unable to read or understand English. Previous exclusion criteria: 1. History of bipolar disorder (due to risk of mania) or depression secondary to other mental disorder 2. Neurological conditions e.g. brain neoplasm, cerebrovascular events, epilepsy, neurodegenerative disorders, and prior brain surgery 3. Standard contradictions to MRI i.e. irremovable metal objects in and around body e.g. cardiac pacemaker, implanted medication pump and pregnancy (any doubt resolved by pregnancy test, women of childbearing age taking precautions against pregnancy). This will include other potential complicated factors such as red tattoos which consist of iron on the head, neck and back and claustrophobia (we offer mock scanner testing and training in some sites) 4. Major unstable medical illness requiring further investigation or treatment 5. Change in prescribed medication in the 2 weeks preceding the start of TMS trial or prescription of lamotrigine, pregabalin, gabapentin or benzodiazepines that act on brain glutamate or GABA (only occasional use of other hypnotic drugs zopiclone, zolpidem, zoleplon and promethazine will be allowed) 6. Current substance abuse or dependence (defined by DSM-5 criteria) 7. Prior TMS treatment 8. At risk of suicidality 9. Potential complicated factors relating to the TMS treatment i.e hairstyles which would impair magnetic transmission and piercings (participants would only be excluded if they chose to not make the changes required to ensure effective treatment) 10. Involved with any other clinical trial at the time of consent or 6 months prior 11. Unable to read or understand English
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 13/10/2021: The efficacy of cgiTBS compared with standard rTMS measured using the Hamilton Depression Rating Scale (HDRS-17) at baseline, 8, 16 and 26 weeks post randomisation date Previous primary outcome measure: The efficacy of cgiTBS at 16 weeks (primary clinical outcome, 50% drop in HDRS-17 score from baseline to 16 weeks) and 26 weeks compared with standard rTMS; in people with TRD ; Timepoint(s): 16 and 26 weeks post randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 13/10/2021: 1. Depression scored using the Hamilton Depression Rating Scale (HDRS-17) score measured at baseline 8, 16 and 26 weeks post randomisation date 2. Remission rate measured using the Hamilton Depression Rating Scale (HDRS-17) score (defined as a score of 8 or less on the HDRS-17) at 8, 16 and 26 weeks 3. Depression symptoms measured using the Beck Depression Inventory 11 (BDI2), a self-rated measure at baseline, 8, 16 and 26 weeks post randomisation date. 4. Cognitive functioning measured using the THINC Integrated Tool (THINCIT), at baseline, 8, 16 and 26 weeks post randomisation date. Due to the pandemic to reduce face to face contact this is only measured at baseline and 16 weeks post randomisation date 5. Self-rated measure of symptoms of depression measured using the Patient Health Questionnaire (PHQ-9) at baseline, 8, 16 and 26 weeks post randomisation date 6. Self-rated measure of anxiety and depression measured using the Generalised Anxiety Disorder Assessment (GAD-7), baseline, 8, 16 and 26 weeks post randomisation date 7. Self-rated measure of impairment in functioning measured using the Work and Social Adjustment Scale (WSAS) at baseline, 8, 16 and 26 weeks post randomisation date 8. Self-rated health utility, quality of life and pain measured using EuroQol-5D-5L, at baseline, 8, 16 and 26 weeks post randomisation date 9. Mood measured using the Quick Inventory of Depressive Symptomology (QIDS-SR16) at baseline, 8 and 16 weeks post randomisation date 10. Patient acceptability and patient experience of overall improvement measured using the Patient Global Impression of Change (1-5 scale very much improved to very much worse) after each treatment session and at 8, 16 and 26 weeks post randomisation date 11. Adverse events measured using a checklist which will be asked after each TMS session 12. Neural mechanism of efficacy in cgiTBS and rTMS measured using FC, eFC, GABA at baseline and 16 weeks post random | — |
Countries
England, United Kingdom
Outcome results
None listed