Transcranial Magnetic Stimulation to Treat Prolonged Grief Disorder

NCT06953596 | Not Yet Recruiting

• 1 other identifier: 23732836368
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Grief is a normal response after the death of a loved one. With time, the grief response decreases and people learn to cope with their loss. However, for some, the response becomes more intense and distressing. This is called prolonged grief disorder (PGD). People with PGD experience emotional pain and a deep longing for their loved one. PGD normally occurs \<10% of people after a loss, but it has become more common since the COVID-19 pandemic (\~30%). If left untreated, PGD leads to poor quality of life and increased risk of death. Treatment options such as medication and therapy are available; however, they can cause negative side effects and take a long time to work. To help individuals with PGD, we need treatments that work well and quickly. Repetitive transcranial magnetic stimulation (rTMS) is a safe, non-invasive treatment that delivers magnetic pulses to brain areas responsible for mood. rTMS has been approved in Canada to treat mood disorders. There is research to show that rTMS is safe and well-tolerated, and that works well in treating Post-Traumatic Stress Disorder (PTSD), a condition with similar symptoms to PGD. To determine whether rTMS is effective for treating PGD, we first need to determine if rTMS as a treatment for PGD is safe and feasible among grieving individuals.

Conditions

Prolonged Grief Disorder; Complicated Grief

Keywords

Neuromodulation; Repetitive Transcranial Magnetic Stimulation; Bereavement; Proof-of-Concept; Feasibility; Intermittent Theta Burst Stimulation (iTBS)

Outcome Measures

Primary Outcomes (6)

• Recruitment Rate

  Number of individuals recruited divided by the recruitment period

  Through study completion, up to 9 months

• Enrollment Rate

  Number of individuals enrolled divided by the number of individuals approached

  Through study completion, up to 9 months

• Intervention Completion Rate

  Number of participants who complete the intervention divided by the number of participants enrolled

  Through study completion, up to 10 months

• Withdrawal Rate

  Number of participants who withdrew divided by the number of participants enrolled

  Through study completion, up to 16 months

• Follow-up Completion Rate

  Number of participants who complete follow-up divided by the number of participants enrolled

  Through study completion, up to 16 months

• Number of Participants with Adverse Events

  Proportion of participants who experience an adverse event

  Through intervention completion, up to 1 week

Secondary Outcomes (5)

• Prolonged Grief Disorder - Global Impression of Change

  Day 5 (last day of intervention), 2-week follow-up, 4-week follow-up, and monthly thereafter for up to 6 months

• Change in Prolonged Grief

  Baseline, day 5 (last day of intervention), 2-week follow-up, 4-week follow-up, and monthly thereafter for up to 6 months

• Prolonged Grief - Change in Post-Traumatic Stress

  Baseline, day 5 (last day of intervention), 2-week follow-up, 4-week follow-up, and monthly thereafter for up to 6 months

• Prolonged Grief - Change in Depression

  Baseline, day 5 (last day of intervention), 2-week follow-up, 4-week follow-up, and monthly thereafter for up to 6 months

• Prolonged Grief - Change in Work and Social Functioning

  Baseline, day 5 (last day of intervention), 2-week follow-up, 4-week follow-up, and monthly thereafter for up to 6 months

Study Arms (1)

rTMS Intervention

EXPERIMENTAL

Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

Interventions

Repetitive Transcranial Magnetic Stimulation (rTMS) DEVICE

Eight rTMS sessions will be administer per day at 60-minute intervals for 5 consecutive days. Each rTMS session will consist of 600 pulses of theta-burst stimulation (iTBS), a pattern of 3 TMS pulses every 200 milliseconds for 2 seconds (i.e., 3 x 50 Hz bursts repeated at 5 Hz) for 3 minutes at 100% of resting motor threshold. The left dorsomedial prefrontal cortex (DMPFC) will be targeted via the Fz EEG site (30% of the nasion-inion distance posteriorly along the nasion-inion line).

rTMS Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Bereaved individuals \>/= 18 years of age
• Score \>25 on the Inventory of Complicated Grief
• Must have a primary care physician
• Ability to understand and communicate in English
• Ability to provide first-person informed consent

You may not qualify if:

• Current or previously diagnosed seizure disorder
• Documented brain lesions
• Contraindications to TMS (i.e., metallic skull plates, clips, stimulators, pacemakers)
• Current substance abuse disorder (e.g., schizophrenia)
• Pregnancy or lactation, or trying to conceive
• Advanced, incurable illness with an expected prognosis of \<3 months - bereaved family members are known to be at elevated risk of death from medical illness, but if death is expected in the near future, it would be difficult to justify using an entire week of their limited time for an unproven therapy.

Sponsors & Collaborators

• Bruyère Health Research Institute.: lead

Study Sites (1)

Bruyere Health

Ottawa, Ontario, K1R 7A5, Canada

Location

Related Publications (12)

• Prigerson HG, Bierhals AJ, Kasl SV, Reynolds CF 3rd, Shear MK, Day N, Beery LC, Newsom JT, Jacobs S. Traumatic grief as a risk factor for mental and physical morbidity. Am J Psychiatry. 1997 May;154(5):616-23. doi: 10.1176/ajp.154.5.616.

  PMID: 9137115 BACKGROUND

• Szuhany KL, Malgaroli M, Miron CD, Simon NM. Prolonged Grief Disorder: Course, Diagnosis, Assessment, and Treatment. Focus (Am Psychiatr Publ). 2021 Jun;19(2):161-172. doi: 10.1176/appi.focus.20200052. Epub 2021 Jun 17.

  PMID: 34690579 BACKGROUND

• Buur C, Zachariae R, Komischke-Konnerup KB, Marello MM, Schierff LH, O'Connor M. Risk factors for prolonged grief symptoms: A systematic review and meta-analysis. Clin Psychol Rev. 2024 Feb;107:102375. doi: 10.1016/j.cpr.2023.102375. Epub 2023 Dec 29.

  PMID: 38181586 BACKGROUND

• Lapenskie J, Anderson K, Lawlor PG, Kabir M, Noel C, Heidinger B, Parsons HA, Cohen L, Gratton V, Besserer E, Adeli S, Murphy R, Warmels G, Bruni A, Bhimji K, Dyason C, Enright P, Desjardins I, Wooller K, Arsenault-Mehta K, Webber C, Bedard D, Iyengar A, Bush SH, Isenberg SR, Tanuseputro P, Vanderspank-Wright B, Downar J. Long-term bereavement outcomes in family members of those who died in acute care hospitals before and during the first wave of COVID-19: A cohort study. Palliat Med. 2024 Feb;38(2):264-271. doi: 10.1177/02692163231223394. Epub 2024 Jan 16.

  PMID: 38229211 BACKGROUND

• Downar J, Parsons HA, Cohen L, Besserer E, Adeli S, Gratton V, Murphy R, Warmels G, Bruni A, Bhimji K, Dyason C, Enright P, Desjardins I, Wooller K, Kabir M, Noel C, Heidinger B, Anderson K, Arsenault-Mehta K, Lapenskie J, Webber C, Bedard D, Iyengar A, Bush SH, Isenberg SR, Tanuseputro P, Vanderspank-Wright B, Lawlor P. Bereavement outcomes in family members of those who died in acute care hospitals before and during the first wave of COVID-19: A cohort study. Palliat Med. 2022 Sep;36(8):1305-1312. doi: 10.1177/02692163221109711. Epub 2022 Jul 4.

  PMID: 35786109 BACKGROUND

• Djelantik AAAMJ, Smid GE, Mroz A, Kleber RJ, Boelen PA. The prevalence of prolonged grief disorder in bereaved individuals following unnatural losses: Systematic review and meta regression analysis. J Affect Disord. 2020 Mar 15;265:146-156. doi: 10.1016/j.jad.2020.01.034. Epub 2020 Jan 13.

  PMID: 32090736 BACKGROUND

• Lundorff M, Holmgren H, Zachariae R, Farver-Vestergaard I, O'Connor M. Prevalence of prolonged grief disorder in adult bereavement: A systematic review and meta-analysis. J Affect Disord. 2017 Apr 1;212:138-149. doi: 10.1016/j.jad.2017.01.030. Epub 2017 Jan 23.

  PMID: 28167398 BACKGROUND

• Kentish-Barnes N, Prigerson HG. Is this bereaved relative at risk of prolonged grief? Intensive Care Med. 2016 Aug;42(8):1279-81. doi: 10.1007/s00134-015-4182-6. Epub 2015 Dec 23. No abstract available.

  PMID: 26699916 BACKGROUND

• Lenferink LIM, van den Munckhof MJA, de Keijser J, Boelen PA. DSM-5-TR prolonged grief disorder and DSM-5 posttraumatic stress disorder are related, yet distinct: confirmatory factor analyses in traumatically bereaved people. Eur J Psychotraumatol. 2021 Dec 9;12(1):1-14. doi: 10.1080/20008198.2021.2000131. eCollection 2021.

  PMID: 34912501 BACKGROUND

• Shear MK, Simon N, Wall M, Zisook S, Neimeyer R, Duan N, Reynolds C, Lebowitz B, Sung S, Ghesquiere A, Gorscak B, Clayton P, Ito M, Nakajima S, Konishi T, Melhem N, Meert K, Schiff M, O'Connor MF, First M, Sareen J, Bolton J, Skritskaya N, Mancini AD, Keshaviah A. Complicated grief and related bereavement issues for DSM-5. Depress Anxiety. 2011 Feb;28(2):103-17. doi: 10.1002/da.20780.

  PMID: 21284063 BACKGROUND

• Tang S, Xiang Z. Who suffered most after deaths due to COVID-19? Prevalence and correlates of prolonged grief disorder in COVID-19 related bereaved adults. Global Health. 2021 Feb 11;17(1):19. doi: 10.1186/s12992-021-00669-5.

  PMID: 33573673 BACKGROUND

• Prigerson HG, Kakarala S, Gang J, Maciejewski PK. History and Status of Prolonged Grief Disorder as a Psychiatric Diagnosis. Annu Rev Clin Psychol. 2021 May 7;17:109-126. doi: 10.1146/annurev-clinpsy-081219-093600. Epub 2021 Feb 1.

  PMID: 33524263 BACKGROUND

MeSH Terms

Conditions

Prolonged Grief Disorder

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Central Study Contacts

James Downar, MDCM, MHSc

CONTACT

613-562-6262; jdownar@toh.ca

Nadia Polskaia, PhD

CONTACT

613-562-6262; npolskaia@bruyere.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, Division of Palliative Care, University of Ottawa

Model Details: Single-centre, single-arm, open-label phase I/II proof-of-concept and feasibility clinical trial

Study Record Dates

• First Submitted: April 22, 2025
• First Posted: May 1, 2025
• Study Start: July 1, 2025
• Primary Completion: March 31, 2026
• Study Completion: April 30, 2026
• Last Updated: May 1, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)