Transcranial Magnetic Stimulation for Psychological Distress in Patients With Advanced Illness

NCT04257227 | Recruiting

• 1 other identifier: M16-19-035
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Psychological and existential distress are a common cause of suffering among patients nearing the end of life, and a major reason for requesting medical aid in dying. Existing treatments for psychological and existential suffering have low efficacy and are challenging to use in a palliative context. There is a need to develop scalable, brief, and rapidly effective therapeutic approaches that can reduce psychological and existential distress in patients nearing the end of life. Repetitive Transcranial Magnetic Stimulation is an effective treatment for refractory depression, and new protocols and increasing availability of rTMS may make this therapy feasible and acceptable for patients who suffer from psychological or existential distress near the end of life. Among patients with advanced illness followed by a PC provider, the study objectives are to:

1. 1.Identify the lowest and range of therapeutic rTMS dose to relieve psychological distress, including an analysis of clinical predictors of response.
2. 2.Test the feasibility and preliminary efficacy of rTMS for the treatment of psychological distress including: 1) ease of recruitment; 2) completion of follow-up; 3) effect size and variance estimates of treatment for primary and secondary outcomes; and 4) patient satisfaction with treatment.

Conditions

Depressive Symptoms; Depression, Anxiety; Psychological Distress; Terminal Illness

Keywords

palliative care; end of life; repetitive transcranial magnetic stimulation; dose-finding; feasibility

Outcome Measures

Primary Outcomes (7)

• Change in Psychological Distress, Depression

  17-Item Hamilton Rating Scale for Depression (HRSD); scores 0-52; higher score is more severe depression

  Baseline (1 day prior to treatment start); after each day of rTMS treatment; 2 weeks, 4, and 8 weeks after intervention completion, if participant is alive

• Change in Psychological Distress, Depression and Anxiety

  The Hospital Anxiety and Depression Scale (HADS); scores 0-21; higher score is more severe anxiety/depression

  Baseline (1 day prior to treatment start); after each day of rTMS treatment; 2 weeks, 4, and 8 weeks after intervention completion, if participant is alive

• Recruitment Rate

  Total number of participants divided by the total number of eligible patients approached

  Measured upon study enrollment termination (estimated at 8 months for dose-finding study)

• Recruitment Rate

  Total number of participants divided by the total number of eligible patients approached

  Measured upon study enrollment termination (estimated at 12 months for feasibility randomized clinical trial)

• Completion of Intervention

  The total number of rTMS sessions completed per day (maximum 8 sessions/day)

  Through intervention completion, up to 1 week

• Completion of Intervention

  The total number of days of rTMS treatment received (maximum 5 days)

  Last day of rTMS treatment, at treatment day 5

• Completion of Follow-up

  Proportion of enrolled participants who complete all assessments at 2 weeks, 4 weeks, and 8 weeks post-intervention

  Upon study completion (up to 20 months)

Secondary Outcomes (4)

• Anxiety

  Baseline (1 day prior to treatment start); end of last rTMS treatment day; 2 weeks, 4 weeks, 8 weeks, and 3 months after intervention completion, if participant is alive

• Existential Distress

  Baseline (1 day prior to treatment start); end of last rTMS treatment day; 2 weeks, 4 weeks, 8 weeks, and 3 months after intervention completion, if participant is alive

• Death Anxiety

  Baseline (1 day prior to treatment start); end of last rTMS treatment day; 2 weeks, 4 weeks, 8 weeks, and 3 months after intervention completion, if participant is alive

• Participant Quality of Life: WHOQOL-Bref

  Baseline (1 day prior to treatment start); end of last rTMS treatment day; 2 weeks, 4 weeks, 8 weeks, and 3 months after intervention completion, if participant is alive

Study Arms (1)

rTMS Intervention Group

EXPERIMENTAL

Device: repetitive Transcranial Magnetic Stimulation (rTMS)

Interventions

repetitive Transcranial Magnetic Stimulation (rTMS) DEVICE

The rTMS intervention will be performed in a dedicated rTMS patient room on the PC unit, where the patient can remain in their bed seated upwards at a 45 degree angle, or seated in a chair. The stimulation intensity for treatment will be determined by measuring the resting and active motor threshold (rMT and aMT) using single pulse TMS over the motor cortex using standard techniques as in previous trials. Investigators will use left-sided intermittent theta burst stimulation (iTBS). The trained team member will locate the left DLPFC using the BeamF3 technique. For the open-label dose-finding study, this region will be stimulated intermittently at 3 TMS pulses every 200 milliseconds for 2 seconds (i.e. 30 stimulations). This procedure is repeated every 10 seconds for a total duration of 3 minutes during which 600 total pulses are delivered. Participants will receive up to 8 3-minute sessions daily at 45 minute intervals for 5 days (consecutively or in a seven-day window if need be).

Also known as: intermittent theta burst stimulation (iTBS)

rTMS Intervention Group

Eligibility Criteria

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

You may qualify if:

• PC unit patients and PC patients in the community with advanced (terminal) illness
• \>1 month life expectancy
• Experiencing psychological distress, as indicated by a score of 7 or greater on the Depression, Anxiety, or Well-being subscale of the Edmonton Symptom Assessment System (ESAS)
• Ability to understand and communicate in English

You may not qualify if:

• Current or previously diagnosed seizure disorder or first-degree relative with current or previously diagnosed seizure disorder
• Documented brain lesions
• Inability to remain still while sitting up (45 degrees) for the duration of therapy
• Known contraindications to rTMS, including: metallic skull plates, clips, or stimulators; pacemakers and other electronic implants; pregnancy; recurrent headaches with no known cause that do not respond to over-the-counter medications; current or previous skull fracture or traumatic brain injury; previous brain surgery; medications that lower seizure threshold

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Lotte & John Hecht Memorial Foundation: collaborator
• Bruyère Health Research Institute.: collaborator
• Canadian Cancer Society (CCS): collaborator

Study Sites (1)

Elisabeth Bruyère Hospital

Ottawa, Ontario, K1N5C8, Canada

RECRUITING

Related Publications (27)

• Bauereiss N, Obermaier S, Ozunal SE, Baumeister H. Effects of existential interventions on spiritual, psychological, and physical well-being in adult patients with cancer: Systematic review and meta-analysis of randomized controlled trials. Psychooncology. 2018 Nov;27(11):2531-2545. doi: 10.1002/pon.4829. Epub 2018 Aug 2.

  PMID: 29958339 BACKGROUND

• Arrieta O, Angulo LP, Nunez-Valencia C, Dorantes-Gallareta Y, Macedo EO, Martinez-Lopez D, Alvarado S, Corona-Cruz JF, Onate-Ocana LF. Association of depression and anxiety on quality of life, treatment adherence, and prognosis in patients with advanced non-small cell lung cancer. Ann Surg Oncol. 2013 Jun;20(6):1941-8. doi: 10.1245/s10434-012-2793-5. Epub 2012 Dec 22.

  PMID: 23263699 BACKGROUND

• Colleoni M, Mandala M, Peruzzotti G, Robertson C, Bredart A, Goldhirsch A. Depression and degree of acceptance of adjuvant cytotoxic drugs. Lancet. 2000 Oct 14;356(9238):1326-7. doi: 10.1016/S0140-6736(00)02821-X.

  PMID: 11073026 BACKGROUND

• Skarstein J, Aass N, Fossa SD, Skovlund E, Dahl AA. Anxiety and depression in cancer patients: relation between the Hospital Anxiety and Depression Scale and the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire. J Psychosom Res. 2000 Jul;49(1):27-34. doi: 10.1016/s0022-3999(00)00080-5.

  PMID: 11053601 BACKGROUND

• Bovero A, Sedghi NA, Opezzo M, Botto R, Pinto M, Ieraci V, Torta R. Dignity-related existential distress in end-of-life cancer patients: Prevalence, underlying factors, and associated coping strategies. Psychooncology. 2018 Nov;27(11):2631-2637. doi: 10.1002/pon.4884. Epub 2018 Sep 24.

  PMID: 30189464 BACKGROUND

• Li M, Watt S, Escaf M, Gardam M, Heesters A, O'Leary G, Rodin G. Medical Assistance in Dying - Implementing a Hospital-Based Program in Canada. N Engl J Med. 2017 May 25;376(21):2082-2088. doi: 10.1056/NEJMms1700606. No abstract available.

  PMID: 28538128 BACKGROUND

• Hendry M, Pasterfield D, Lewis R, Carter B, Hodgson D, Wilkinson C. Why do we want the right to die? A systematic review of the international literature on the views of patients, carers and the public on assisted dying. Palliat Med. 2013 Jan;27(1):13-26. doi: 10.1177/0269216312463623. Epub 2012 Nov 5.

  PMID: 23128904 BACKGROUND

• Salt S, Mulvaney CA, Preston NJ. Drug therapy for symptoms associated with anxiety in adult palliative care patients. Cochrane Database Syst Rev. 2017 May 18;5(5):CD004596. doi: 10.1002/14651858.CD004596.pub3.

  PMID: 28521070 BACKGROUND

• Lo C, Hales S, Jung J, Chiu A, Panday T, Rydall A, Nissim R, Malfitano C, Petricone-Westwood D, Zimmermann C, Rodin G. Managing Cancer And Living Meaningfully (CALM): phase 2 trial of a brief individual psychotherapy for patients with advanced cancer. Palliat Med. 2014 Mar;28(3):234-42. doi: 10.1177/0269216313507757. Epub 2013 Oct 29.

  PMID: 24170718 BACKGROUND

• Chochinov HM, Kristjanson LJ, Breitbart W, McClement S, Hack TF, Hassard T, Harlos M. Effect of dignity therapy on distress and end-of-life experience in terminally ill patients: a randomised controlled trial. Lancet Oncol. 2011 Aug;12(8):753-62. doi: 10.1016/S1470-2045(11)70153-X. Epub 2011 Jul 6.

  PMID: 21741309 BACKGROUND

• Downar J, Blumberger DM, Daskalakis ZJ. Repetitive transcranial magnetic stimulation: an emerging treatment for medication-resistant depression. CMAJ. 2016 Nov 1;188(16):1175-1177. doi: 10.1503/cmaj.151316. Epub 2016 Aug 22. No abstract available.

  PMID: 27551033 BACKGROUND

• Tik M, Hoffmann A, Sladky R, Tomova L, Hummer A, Navarro de Lara L, Bukowski H, Pripfl J, Biswal B, Lamm C, Windischberger C. Towards understanding rTMS mechanism of action: Stimulation of the DLPFC causes network-specific increase in functional connectivity. Neuroimage. 2017 Nov 15;162:289-296. doi: 10.1016/j.neuroimage.2017.09.022. Epub 2017 Sep 12.

  PMID: 28912081 BACKGROUND

• Blumberger DM, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, Knyahnytska Y, Kennedy SH, Lam RW, Daskalakis ZJ, Downar J. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Lancet. 2018 Apr 28;391(10131):1683-1692. doi: 10.1016/S0140-6736(18)30295-2. Epub 2018 Apr 26.

  PMID: 29726344 BACKGROUND

• Brunelin J, Jalenques I, Trojak B, Attal J, Szekely D, Gay A, Januel D, Haffen E, Schott-Pethelaz AM, Brault C; STEP Group; Poulet E. The efficacy and safety of low frequency repetitive transcranial magnetic stimulation for treatment-resistant depression: the results from a large multicenter French RCT. Brain Stimul. 2014 Nov-Dec;7(6):855-63. doi: 10.1016/j.brs.2014.07.040. Epub 2014 Aug 7.

  PMID: 25192980 BACKGROUND

• McGirr A, Van den Eynde F, Tovar-Perdomo S, Fleck MP, Berlim MT. Effectiveness and acceptability of accelerated repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depressive disorder: an open label trial. J Affect Disord. 2015 Mar 1;173:216-20. doi: 10.1016/j.jad.2014.10.068. Epub 2014 Nov 11.

  PMID: 25462419 BACKGROUND

• Fitzgerald PB, Hoy KE, Elliot D, Susan McQueen RN, Wambeek LE, Daskalakis ZJ. Accelerated repetitive transcranial magnetic stimulation in the treatment of depression. Neuropsychopharmacology. 2018 Jun;43(7):1565-1572. doi: 10.1038/s41386-018-0009-9. Epub 2018 Feb 5.

  PMID: 29467437 BACKGROUND

• Baeken C, Marinazzo D, Wu GR, Van Schuerbeek P, De Mey J, Marchetti I, Vanderhasselt MA, Remue J, Luypaert R, De Raedt R. Accelerated HF-rTMS in treatment-resistant unipolar depression: Insights from subgenual anterior cingulate functional connectivity. World J Biol Psychiatry. 2014 May;15(4):286-97. doi: 10.3109/15622975.2013.872295. Epub 2014 Jan 21.

  PMID: 24447053 BACKGROUND

• Holtzheimer PE 3rd, McDonald WM, Mufti M, Kelley ME, Quinn S, Corso G, Epstein CM. Accelerated repetitive transcranial magnetic stimulation for treatment-resistant depression. Depress Anxiety. 2010 Oct;27(10):960-3. doi: 10.1002/da.20731.

  PMID: 20734360 BACKGROUND

• Fitzgerald PB, Hoy K, Gunewardene R, Slack C, Ibrahim S, Bailey M, Daskalakis ZJ. A randomized trial of unilateral and bilateral prefrontal cortex transcranial magnetic stimulation in treatment-resistant major depression. Psychol Med. 2011 Jun;41(6):1187-96. doi: 10.1017/S0033291710001923. Epub 2010 Oct 7.

  PMID: 20925972 BACKGROUND

• Cooper YA, Pianka ST, Alotaibi NM, Babayan D, Salavati B, Weil AG, Ibrahim GM, Wang AC, Fallah A. Repetitive transcranial magnetic stimulation for the treatment of drug-resistant epilepsy: A systematic review and individual participant data meta-analysis of real-world evidence. Epilepsia Open. 2017 Dec 27;3(1):55-65. doi: 10.1002/epi4.12092. eCollection 2018 Mar.

  PMID: 29588988 BACKGROUND

• Hamilton M. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol. 1967 Dec;6(4):278-96. doi: 10.1111/j.2044-8260.1967.tb00530.x. No abstract available.

  PMID: 6080235 BACKGROUND

• Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361-70. doi: 10.1111/j.1600-0447.1983.tb09716.x.

  PMID: 6880820 BACKGROUND

• Kissane DW, Wein S, Love A, Lee XQ, Kee PL, Clarke DM. The Demoralization Scale: a report of its development and preliminary validation. J Palliat Care. 2004 Winter;20(4):269-76.

  PMID: 15690829 BACKGROUND

• Templer DI. The construction and validation of a Death Anxiety Scale. J Gen Psychol. 1970 Apr;82(2d Half):165-77. doi: 10.1080/00221309.1970.9920634. No abstract available.

  PMID: 4394812 BACKGROUND

• 46. World Health Organization. WHOQOL-BREf: Introduction, administration, scoring, and generic version of the assessment. Dec 1996. Retrieved from: https://www.who.int/mental_health/media/en/76.pdf

  BACKGROUND

• Oberman L, Edwards D, Eldaief M, Pascual-Leone A. Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. J Clin Neurophysiol. 2011 Feb;28(1):67-74. doi: 10.1097/WNP.0b013e318205135f.

  PMID: 21221011 BACKGROUND

• Downar J, Lapenskie J, Anderson K, Edwards J, Watt C, Dionne M, Rice J, Kabir M, Lawlor P, Downar J. Accelerated transcranial magnetic stimulation for psychological distress in advanced cancer: A phase 2a feasibility and preliminary efficacy clinical trial. Palliat Med. 2024 Apr;38(4):485-491. doi: 10.1177/02692163241234799. Epub 2024 Mar 14.

  PMID: 38482823 DERIVED

MeSH Terms

Conditions

Depression; Anxiety Disorders; Death

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Central Study Contacts

James Downar, MDCM, MHSc

CONTACT

6135626262; jdownar@toh.ca

Julie Lapenskie, MSc

CONTACT

613-562-6262; jlapenskie@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: SPONSOR

Model Details: Open-label dose-finding study, to be followed by either a sham-crossover or sham-control randomized clinical trial based on results of the dose-finding study. Study design described here is for the dose-finding study, and information will be updated once the randomized clinical trial is started.

Study Record Dates

• First Submitted: December 11, 2019
• First Posted: February 5, 2020
• Study Start: November 2, 2020
• Primary Completion: January 20, 2025
• Study Completion: January 20, 2025
• Last Updated: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)