A Pilot fMRI Study of TMS in Late-Life Severe Worry

NCT03577106 | Completed Results FDA Device

• 1 other identifier: STUDY19020109
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators will test a novel intervention through experimental therapeutic approach using fMRI-directed Intermittent Theta Burst Stimulation (iTBS), a high frequency TMS paradigm, for the treatment of severe, uncontrollable worry. While worry is a universal human experience, severe and excessive worry has been recently linked to increased risk of stroke and other cardiovascular diseases, increased risk of conversion to Alzheimer's disease as well as to higher risk of all-cause mortality in midlife and late-life. Severe, uncontrollable worry has been repeatedly associated with reduced quality of life and impaired functioning. Current treatment choices (antidepressant/anxiolytic medications and psychotherapeutic interventions) have been proven moderately efficacious in reducing anxiety/depression burden, but ineffective in reducing worry severity, a phenomenon that may contribute to the high relapse rates associated with mood and anxiety disorders. Our research indicated that worry severity is associated with hyperactivation in specific regions such as orbital frontal cortex, superior parietal gyrus, amygdala and parahippocampal gyrus. This pilot study will explore the efficacy of targeting one of these regions with iTBS. Based on investigators' previous results, the most accessible target is the right superior parietal gyrus (rSPG) - a region that remained significantly associated with severe worry after controlling for effects of comorbid depression or overall anxiety. As this region showed an increased in cerebrovascular flow in association with worry severity, investigators will use iTBS (5x/week for 2 weeks) to modulate cortical plasticity in this region and consequently, to reduce worry severity. TMS during wakefulness has been shown to alter subsequent sleep \[4\], Further, changes in sleep in response to TMS has been associated with how participants respond to the TMS as a treatment \[5\]. Thus, the study will measure sleep throughout the protocol to determine whether sleep changes as a function of TMS and whether sleep changes are associated with treatment response.

Conditions

Anxiety Disorders Generalized

Keywords

transcranial magnetic stimulation; TMS; MRI; magnetic resonance imaging; fMRI; functional magnetic resonance imaging; sleep; intermittent theta burst stimulation; iTBS

Outcome Measures

Primary Outcomes (2)

• Change in Worry Severity From Baseline to Post-intervention as Measured by the Penn State Worry Questionnaire (PSWQ)

  Penn State Worry Questionnaire (PSWQ) scores range from 16 to 80 with higher levels indicating greater worry severity.

  Baseline and within 2 weeks post-TMS intervention

• Participants Who Responded to TMS

  The breakdown of participants who responded to TMS treatment; responders had Penn State Worry Questionnaire (PSWQ) scores that decreased by 30% or more from the baseline timepoint to the end of TMS treatment.

  Baseline and the end of TMS intervention (approximately two weeks)

Study Arms (1)

Transcranial magnetic stimulation (TMS)

EXPERIMENTAL

Device: Transcranial magnetic stimulation (TMS)

Interventions

Transcranial magnetic stimulation (TMS) DEVICE

Theta Burst Stimulation (TBS), a form of TMS, will be targeted to the Inferior Parietal Cortex based on neural navigation software. TBS will be delivered for about 5-6 minutes, five days a week for two weeks, for a total of ten sessions.

Transcranial magnetic stimulation (TMS)

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have completed Dr. Andreescu's study R01MH108509/PRO15080120.
• Penn State Worry Questionnaire score of 55 or above.

You may not qualify if:

• Any form of psychosis or Bipolar Disorder, dementia, a history of substance abuse within the last six months
• Use of antidepressants within the last five to fourteen days (adequate washout interval to be determined by the principal investigator (PI) based on each specific antidepressant). For fluoxetine, the washout interval will be six weeks. However, for participants who are prescribed low dose psychotropics for pain, sleep disturbances, and/or medical conditions (e.g. amitriptyline for peripheral neuropathy, low dose trazodone as a sleep aid), these will be allowed in most circumstances. We will include participants on certain dosages of the most commonly prescribed antidepressants (for medical reasons) as follows: amitriptyline up to 50 mg/d, doxepin up to 50 mg/d, trazodone up to 100 mg/d, and imipramine up to 50 mg/d. We will review other cases individually and the PI will decide if the participants are eligible for the study and if they may continue the current medication.
• Unable to complete MRI scans: presence of ferromagnetic metal in the body, claustrophobia
• Contraindications for TMS:
• Presence of a neurologic disorder or medical condition known to alter seizure threshold(e.g., stroke, aneurysm, brain surgery, structural brain lesion, brain injury, frequent/severe headaches)
• Recurrent seizures or epilepsy in participant
• Pregnancy
• Metallic implants in body located at 30 cm or less from the position of the magnetic coil; presence in the body of other devices that may be affected by magnetic field (e.g. pacemakers).
• Unable to temporarily discontinue benzodiazepines 48 hours prior to MRI scan. Participants on high doses of benzodiazepines (e.g., greater than or equivalent to 2 mg of lorazepam) will be excluded, given the complexity and potential complications of benzodiazepine taper/withdrawal.

Sponsors & Collaborators

• Carmen Andreescu: lead

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (4)

• Saeki T, Nakamura M, Hirai N, Noda Y, Hayasaka S, Iwanari H, Hirayasu Y. Localized potentiation of sleep slow-wave activity induced by prefrontal repetitive transcranial magnetic stimulation in patients with a major depressive episode. Brain Stimul. 2013 May;6(3):390-6. doi: 10.1016/j.brs.2012.08.004. Epub 2012 Aug 31.

  PMID: 22964349 BACKGROUND

• Rosenquist PB, Krystal A, Heart KL, Demitrack MA, McCall WV. Left dorsolateral prefrontal transcranial magnetic stimulation (TMS): sleep factor changes during treatment in patients with pharmacoresistant major depressive disorder. Psychiatry Res. 2013 Jan 30;205(1-2):67-73. doi: 10.1016/j.psychres.2012.09.011. Epub 2012 Sep 25.

  PMID: 23021320 BACKGROUND

• Golden J, Conroy RM, Bruce I, Denihan A, Greene E, Kirby M, Lawlor BA. The spectrum of worry in the community-dwelling elderly. Aging Ment Health. 2011 Nov;15(8):985-94. doi: 10.1080/13607863.2011.583621. Epub 2011 Jul 12.

  PMID: 21749221 BACKGROUND

• Tully PJ, Cosh SM, Baune BT. A review of the affects of worry and generalized anxiety disorder upon cardiovascular health and coronary heart disease. Psychol Health Med. 2013;18(6):627-44. doi: 10.1080/13548506.2012.749355. Epub 2013 Jan 16.

  PMID: 23324073 BACKGROUND

MeSH Terms

Conditions

Generalized Anxiety Disorder

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Limitations and Caveats

Due to COVID, we were only able to recruit a total of 21 participants instead of 40 who were to complete full treatment. The treatment was only a typical 'half' dose consisting of 10 sessions of TMS rather than 20, which is typical. Three participants started TMS and decided to withdraw due to discomfort from TMS.

Results Point of Contact

• Title: Scott Ward
• Organization: UPMC

wards7@upmc.edu

412-683-7105

Study Officials

• Carmen Andreescu, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 31, 2018
• First Posted: July 5, 2018
• Study Start: December 6, 2018
• Primary Completion: May 4, 2022
• Study Completion: May 4, 2022
• Last Updated: June 22, 2023
• Results First Posted: June 22, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)