Dutch-Depression Outcome Trial Comparing 5 Day Multi Daily Neuronavigated Theta Burst Sessions With 6 Weeks rTMS

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.

Conditions

• Treatment Resistant Depression

Interventions

DEVICE

rTMS

10 Hz repetitive-transcranial-magnetic-stimulation

DEVICE

iTBS

neuronavigated intermittent theta burst transcranial-magnetic-stimulation

Sponsors & Collaborators

• Radboud University Medical Center

  collaborator OTHER

• Maastricht University Medical Center

  collaborator OTHER

• Maastricht University

  collaborator OTHER

• Trimbos

  collaborator UNKNOWN

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  collaborator OTHER

• Donders Centre for Neuroscience

  collaborator OTHER

• Amsterdam UMC, location VUmc

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

99 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-11-15

Primary Completion

2027-04-30

Completion

2027-12-31

Countries

• Netherlands

Study Locations