NCT05900271

Brief Summary

INTRODUCTION Recent findings from three small studies (total n=59) suggest that three changes in repetitive Transcranial Magnetic Stimulation (rTMS) protocols, called the Stanford Neuromodulation Therapy (SNT) protocol, contribute to extreme high overall remission of 79% in patients with treatment resistant depression (TRD), whereas remission using a standard 10 Hz rTMS protocol is 25%. The improvement using the SNT protocol is achieved by combining 1) accelerated treatment with multiple sessions per day, 2) applying a higher overall pulse dose of stimulation, using intermittent Theta Burst Stimulation (iTBS), and 3) precise targeting of the region in the left dorsolateral prefrontal cortex (DLPFC), using functional MRI guided neuronavigation. OBJECTIVE To determine if the SNT protocol is more (cost-) effective compared to standard 10 Hz rTMS in patients with TRD, even though the number of pulses given in both protocols is equal, i.e., 90,000. STUDY DESIGN Multicenter randomized controlled trial comparing SNT with standard 10Hz rTMS with a follow-up of 25 weeks. STUDY POPULATION 108 Patients with TRD (no response to 2 or more evidence-based treatments). INTERVENTION 50 sessions using the SNT protocol in 5 days. The region of the left DLPFC most anticorrelated with the subgenual anterior cingulate cortex in each participant will be targeted based on subject-specific functional resting state MRI. COMPARISON 30 standard daily 10 Hz rTMS sessions in six weeks, targeting the left DLPFC based on standard measurement procedures of the skull. OUTCOME MEASURES

  • Remission, based on the Hamilton depression rating scale
  • Cost effectiveness, based on healthcare resource use
  • Quality of life and positive mental health
  • Tolerability and safety
  • Relapse
  • Description of opportunities and difficulties with regard to implementation SAMPLE SIZE The investigators will enrol 108 patients (α=0.05, power is 0.80) including adjustment for attrition. COST EFFECTIVENESS ANALYSIS SNT is faster and possibly more effective than 10Hz rTMS leading to a total cost reduction of 22 million each year considering less expensive healthcare, reduced illness duration and absence from work. TIME SCHEDULE Within 36 months, the investigators will recruit and treat 108 patients with TRD: each center will recruit 9 patients per year. After the last follow-up assessments, the investigators will finalise the study within 12 months and report the results.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
108

participants targeted

Target at P50-P75 for not_applicable

Timeline
19mo left

Started Nov 2023

Longer than P75 for not_applicable

Geographic Reach
1 country

4 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress61%
Nov 2023Dec 2027

First Submitted

Initial submission to the registry

May 10, 2023

Completed
1 month until next milestone

First Posted

Study publicly available on registry

June 12, 2023

Completed
5 months until next milestone

Study Start

First participant enrolled

November 15, 2023

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2027

Expected
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2027

Last Updated

April 5, 2024

Status Verified

April 1, 2024

Enrollment Period

3.4 years

First QC Date

May 10, 2023

Last Update Submit

April 4, 2024

Conditions

Treatment Resistant Depression

Keywords

TMStreatment resistant depression

Outcome Measures

Primary Outcomes (1)

  • Remission

    Clinical outcome is remission, which is defined as a score of 7 or lower on the clinician-rated HDRS-17 (17-itemHamilton Depression Rating Scale, scores 0-52 with higher score indicating worse outcome) measured one week after the last treatment session.

    After 1 week.

Secondary Outcomes (5)

  • Health-related quality of life

    After 1-, 5-, 10- and 25-weeks.

  • Self-rated depressive symptoms

    After 1-, 5-, 10- and 25-weeks.

  • Relapse

    After1-, 5-, 10- and 25-weeks.

  • Side-effects

    After 1- and 6- weeks.

  • Remission

    5-, 10- and 25-weeks after the last treatment session.

Study Arms (2)

intermittent theta burst transcranial magnetic stimulation (iTBS)

EXPERIMENTAL

5-day multi daily neuronavigated intermittent theta burst sessions (developed by Stanford University) and coined, SNT, i.e., Stanford NeuromdulaTion protocol

Device: iTBS

10 Hz repetitive-transcranial-magnetic-stimulation (rTMS)

ACTIVE COMPARATOR

6-weeks standard 10 Hz rTMS

Device: rTMS

Interventions

rTMSDEVICE

10 Hz repetitive-transcranial-magnetic-stimulation

10 Hz repetitive-transcranial-magnetic-stimulation (rTMS)
iTBSDEVICE

neuronavigated intermittent theta burst transcranial-magnetic-stimulation

intermittent theta burst transcranial magnetic stimulation (iTBS)

Eligibility Criteria

Age18 Years - 99 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • years of age or older;
  • Sufficient level of spoken and written Dutch;
  • Ability to freely provide written informed consent;
  • Current DSM-5 diagnosis of a depressive episode, ascertained by the Mini International Neuropsychiatry Interview (MINI-S).
  • A Hamilton depression rating score (HDRS) of \>16 points: this score will be obtained from the SIGH-ADS, a depression rating scale able to determine the HDRS score and a score for atypical depression.
  • have a treatment resistant depression, defined according to the criteria of Conway, that is, lack of remission for eight consecutive weeks after two different evidence-based treatments anti-depressant medication has to be adequately dosed(7,24).
  • Stable anti-depressant medication 6 weeks prior to study. Benzodiazepines may be used up to a dosage equivalent of 3.0 mg lorazepam, and can be lowered over time during the study based on clinical judgement.

You may not qualify if:

  • \- Bipolar disorder.
  • Current psychotic disorder¸ including psychotic depression, assessed by treating psychiatrist.
  • Active suicidal thoughts and intent to act on it, assessed at the baseline interview and before the start of the trial. This assessment is based on the Columbia suicide severity rating scale, i.e., question 5 is answered positive "Have you started to work out or worked out the details of how to kill yourself? Do you intend to carry out this plan?" (26).
  • Metallic devices implanted above the neck, assessed at the baseline interview.
  • Patients diagnosed with epilepsy, by a neurologist, assessed at the baseline interview.
  • Substance abuse 4 weeks prior to the study, including high dosage of benzodiazepine, a dosage equivalent higher than 3.0 mg lorazepam, assessed at the baseline interview.
  • Inability to understand or comply with study requirements as judged by the investigators, assessed at the baseline interview.
  • Pregnancy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Radboud UMC

Nijmegen, GL, 6525GA, Netherlands

RECRUITING

GGZinGeest

Amsterdam, North Holland, 1081JC, Netherlands

RECRUITING

Amsterdam UMC location AMC

Amsterdam-Zuidoost, North Holland, 1105AZ, Netherlands

RECRUITING

Maastricht UMC

Maastricht, Netherlands

NOT YET RECRUITING

Related Publications (1)

  • Dols A, Biemans T, Coomans C, van Eijndhoven P, Dalhuisen I, van der Werf YD, Vriend C, Gomes ESA, Sack AT, Schuhmann T, Chaudhry M, Arns M, Walters BH, Wijnen B, Zalesky A, Cash R, Blumberger DM, Scheepstra KW, Hoogendoorn AW, van den Heuvel OA, van Exel E; D-DOTT Consortium. Comparison of 5-Day Multidaily Neuronavigated Theta-Burst Sessions With 6-Week Standard Repetitive Transcranial Magnetic Stimulation (the Dutch Depression Outcome Trial): Protocol for a Randomized Controlled Trial. JMIR Res Protoc. 2025 Aug 21;14:e70121. doi: 10.2196/70121.

    PMID: 40840870DERIVED

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental Disorders

Central Study Contacts

Annemiek Dols, MD PhD

CONTACT

0610445878a.dols@amsterdamumc.nl

Eric van Exel, MD PhD

CONTACT

+31204444444e.vexel@amsterdamumc.nl

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
Those carrying out clinical assessments will be blinded. However, participants and those who will be administering the rTMS or SNT treatment will not be blinded. Participants and research staff will be requested not to reveal information about treatment allocation to the raters.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: multicentre, two-phase, randomized clinical trial
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
psychiatrist and researcher

Study Record Dates

First Submitted

May 10, 2023

First Posted

June 12, 2023

Study Start

November 15, 2023

Primary Completion (Estimated)

April 1, 2027

Study Completion (Estimated)

December 1, 2027

Last Updated

April 5, 2024

Record last verified: 2024-04

Data Sharing

IPD Sharing
Will not share

Locations

NL(4)