iTBS Study for Depression (Randomized)

NCT03745768 | Completed Results FDA Device

• 1 other identifier: 201803023
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Executive function deficits are common in late life depression (LLD) and are associated with resistance to antidepressants, poor quality of life, considerable disability and increased suicidal risk. This study uses a novel type of Transcranial Magnetic Stimulation called intermittent Theta Burst Stimulation (iTBS). iTBS delivers high frequency (50Hz) magnetic pulses in "bursts" of 3 stimuli. It is posited that this intervention induces plasticity in the human cortex. Theoretical and empirical evidence from research studies informs that iTBS can improve depression and executive deficits, however, this has not been examined in older adults. This project examines iTBS's ability to improve depression and executive impairment in LLD. It also tests the effects of iTBS on brain connectivity within the Cognitive Control Network (CCN). This study will enhance understanding of LLD, providing critical pilot data to develop future randomized controlled clinical trials. Both active and sham interventions are administered sequentially to the left and right dorso-lateral prefrontal cortex. The total stimulation time is about 7 minutes. These interventions are administered for 6 weeks (Monday-Friday). 20 subjects will be randomized. Changes in mood from baseline to the end of study are measured with the Montgomery-Asberg Depression Rating Scale. Executive function at baseline and end of study are evaluated with the National Institutes of Health Toolbox executive domain battery. Safety assessments include: the 21 item Scale for suicidal ideation SSI. The frequency, intensity and burden of side effects rating (FIBSER) and the Altman Self Rating Mania scale (ASRM). Ancillary depression measures include the Quick Inventory of Depressive Symptoms (QIDS) and the Clinical Global Impression of Improvement scale. Subjects undergo functional Magnetic Resonance Imaging (fMRI) before and after the study interventions to test the effects of iTBS on the brain's functional connectivity. This research will provide meaningful information about the effects of iTBS on mood and executive function in older adults as well as information regarding its effects on brain function. Results of this pilot study will inform a grant submission and allow investigators to calculate power for a definitive randomized controlled clinical trial to test the efficacy of iTBS versus placebo.

Conditions

Executive Dysfunction; Depression

Keywords

depression; executive dysfunction; transcranial magnetic stimulation; intermittent theta burst stimulation; neuromodulation; older adults; geriatrics

Outcome Measures

Primary Outcomes (6)

• Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores From Baseline to the End of the Intervention

  We will assess the efficacy of iTBS in improving mood by determining if older adults randomized to iTBS will show significant decreases in the Montgomery-Asberg Depression Rating Scale consistent with improvement of depressive symptoms. The total score for the scale will be reported. The total scores range is 0 - 60 with 0 = minimum score and 60 the maximum score. A low score is better as it denotes less depressive symptoms.

  6 weeks

• Change in the NIH Toolbox Executive Domain Measure Flanker Inhibitory Control and Attention Test

  Improvement in executive function in participants will be assessed by determining if subjects randomized to iTBS show significant increases in their NIH Toolbox Flanker Inhibitory control and attention test from baseline to the end of 6 weeks, compared to those randomized to sham. NIH Tool box Flanker inhibitory control and attention test is a validated instrument measuring attention and inhibitory control. The age corrected standard score is used, for which the normative mean is 100 and the standard deviation is 15. This score compares the score of the test taker to those in the NIH tool box nationally representative sample at the same age, where a score of 100 indicates performance that was at the national average for the test-taking participant's age. A score of 115 or 85 for example would indicate that the participant's performance is 1SD above or below the national average respectively, when compared with like-aged participants. Higher scores indicate higher performance.

  6 weeks

• Change in the NIH Tool Box Executive Measure Dimensional Change Card Sort Test

  Improvement in executive function in participants will be assessed by determining if subjects randomized to iTBS show significant increases in their NIH Toolbox Dimensional change card sort test from baseline to the end of 6 weeks, compared to those randomized to sham. NIH Tool box Dimensional change card sort test is a validated instrument measuring cognitive flexibility. The age corrected standard score is used, for which the normative mean is 100 and the standard deviation is 15. This score compares the score of the test taker to those in the NIH tool box nationally representative sample at the same age, where a score of 100 indicates performance that was at the national average for the test-taking participant's age. A score of 115 or 85 for example would indicate that the participant's performance is 1SD above or below the national average respectively, when compared with like-aged participants. Higher scores indicate higher performance.

  6 weeks

• Change in the NIH Tool Box List Sorting Working Memory Measure

  Improvement in executive function in participants will be assessed by determining if subjects randomized to iTBS show significant increases in their NIH Toolbox list sorting working memory test from baseline to the end of 6 weeks, compared to those randomized to sham. NIH Tool box list sorting working memory test is a validated instrument measuring working memory. The age corrected standard score is used, for which the normative mean is 100 and the standard deviation is 15. This score compares the score of the test taker to those in the NIH tool box nationally representative sample at the same age, where a score of 100 indicates performance that was at the national average for the test-taking participant's age. A score of 115 or 85 for example would indicate that the participant's performance is 1SD above or below the national average respectively, when compared with like-aged participants. Higher scores indicate higher performance.

  6 weeks

• Connectivity Change Within the CNN, Fronto-parietal Network

  We will test the effects of iTBS on functional connectivity within the CNN ( fronto-parietal network) in depressed older adults obtained using resting state fMRI measuring BOLD signal in the brain. Depressed older adults randomized to iTBS versus sham will have a significant increase in functional connectivity within the fronto-parietal network from baseline to week 6.

  6 weeks

• Connectivity Change Within the CNN, Cingulo Opercular Network

  We will test the effects of iTBS on functional connectivity within the CNN cingulo opercular network in depressed older adults obtained using resting state fMRI measuring bold signal in the brain. Depressed older adults randomized to iTBS versus sham will have a significant increase in functional connectivity within the cingulo-opercular network from baseline to week 6.

  6 weeks

Study Arms (2)

Active iTBS Treatment

EXPERIMENTAL

Participants received Intermittent theta burst stimulation to the dorsolateral prefrontal cortex for 6 weeks

Device: Intermittent Theta Burst Stimulation

Sham Stimulation

SHAM COMPARATOR

Participants received Sham stimulation to the dorsolateral prefrontal cortex for 6 weeks.

Device: sham stimulation

Interventions

Intermittent Theta Burst Stimulation DEVICE

Intermittent theta burst stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain for 6 weeks.

Active iTBS Treatment

sham stimulation DEVICE

Sham stimulation delivered to the dorsolateral prefrontal cortex on the left and right sides of the brain for 6 weeks.

Sham Stimulation

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 60 - 85 years old
• Diagnosis of major depressive disorder (MDD), single or recurrent, with a current Major depression episode as diagnosed by the Mini-international Neuropsychiatric Interview (MINI 6.0)
• Montgomery Asberg Depression Scale score greater than or equal to 15 at baseline.
• Evidence of decreased executive function as evidenced by either of the following conditions: a) scoring below the mean normative scaled score on the average of the NIH Toolbox executive function measures: Flanker inhibitory control and attention test and the Dimensional sort card test, approximate score 70 - 100 as per PI discretion. b) Discrepancy of at least 10 points between the average of the picture vocabulary score and the reading recognition test score and the average of the Flanker inhibitory control and dimensional card sort test score. c) Frontal Systems Behavior Scale (FRSBE) T scores above 60 (indicative of borderline to clinically significant impairment) and at least 10 points (1 Standard Deviation) above subject's premorbid (pre-depression) scores.

You may not qualify if:

• Inability to complete NIH tool box cognitive testing
• Inability to provide informed consent
• \<22 score on the Montreal Cognitive Assessment MoCA indicative of moderate to severe cognitive impairment per PI discretion
• Lifetime diagnosis of bipolar I or II disorder or psychotic disorder as per the MINI interview
• current psychotic symptoms
• alcohol or other substance use disorder per DSM V criteria in the past 6 months
• High risk for suicide (active suicidal ideation/intent or plan and patient is unsafe to be in the outpatient setting), an urgent psychiatric referral will be made in those cases
• Have a diagnosis of obsessive compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalized anxiety disorder, social anxiety disorder, panic disorder), assessed by a study investigator to be primary
• Previous history of TMS
• history of failure to an adequate course of electroconvulsive therapy (ECT) such as equal or more than 7-9 electroconvulsive therapy treatments, per PI discretion
• Major unstable medical illness including advanced/uncontrolled diabetes, hypertension, renal disease or advanced cancer, per PI discretion
• Psychotropic use other than antidepressants (e.g., Benzodiazepines \[more than 2mg of lorazepam equivalent daily\], anticonvulsants \[except low dose of Neurontin approximately 600mg/day\] or cognitive enhancers such as N-Methyl D - Aspartate (NDMA) receptor antagonists \[Memantine HCL\], psychostimulants \[such as methylphenidate or modafinil\]) per PI discretion
• Recent changes or initiation of antidepressant therapy approximately in the last 4 weeks prior to intervention delivery, per PI discretion
• if participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study
• contraindications for TMS including the presence of metallic objects within 30 cm of the TMS coil, intracranial implants (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed; presence of intracardiac lines, defibrillators or a cardiac pacemaker and unable to assess safety; presence of implanted electronic devices that control physiologic functions and unable to assess safety

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University in St. Louis School of Medicine - Healthy Mind Lab

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Depression

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Results Point of Contact

• Title: Pilar Cristancho M.D.
• Organization: Washington University School of Medicine St. Louis

cristanchopimiento.l@wustl.edu

314 362 2413

Study Officials

• Pilar Cristancho, MD

  Washington University School of Medicine in St. Louis

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized controlled clinical trial testing iTBS versus sham

Study Record Dates

• First Submitted: November 14, 2018
• First Posted: November 19, 2018
• Study Start: April 5, 2018
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: July 6, 2022
• Results First Posted: July 6, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Upon publication pf study results
• Access Criteria: to request information e-mail PI: Pilar Cristancho at cristanchopimiento.l@wustl.edu

Locations

US (1)