Transcranial Magnetic Stimulation (TMS) for Patients With Exposure Therapy-resistant Obsessive-compulsive Disorder (OCD): TETRO - a Multicenter Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 250
- 试验地点
- 8
- 主要终点
- Y-BOCS
研究概览
简要总结
TETRO is a multi-center placebo-controlled double-blind randomized controlled trial with an intervention phase of 5-7 weeks and a follow-up phase of 12 months in 250 adult (18 years and older) OCD patients who show no/insufficient response to ERP, aiming to establish the cost-effectiveness of low frequency (1 Hz) rTMS to the pre-SMA (compared to sham rTMS to the pre-SMA) as adjuvant treatment to exposure with response prevention (ERP). The treatment consists of 4 times/week rTMS combined with ERP for at least 5 weeks (20 sessions), with optional extension phase of 1 or 2 weeks (maximum of 28 sessions in total).
详细描述
Rationale:
Obsessive-compulsive disorder (OCD) is a serious and disabling mental disorder, characterized by obsessions and compulsions and associated with substantial comorbidity and morbidity (Stein et al. 2019). Approximately 50% of patients treated with standard treatments (exposure therapy with response prevention (ERP) with/without medication) fail to respond fully, resulting in chronicity and poor participation in social and educational/occupational domains. We propose to fill the gap between the standard treatments (exposure therapy with/without medication) on the one side and invasive end-stage strategies (brain surgery) on the other side, using a non-invasive alternative: repetitive transcranial magnetic stimulation (rTMS). Despite proven efficacy (Zhou et al. 2017; Rehn et al. 2018; Fitzsimmons et al. 2022), rTMS for OCD is not yet covered by the Dutch insurance system while rTMS for treatment resistant depression is. This multi-center randomized controlled trial, supported by the 'veelbelovende zorg' grant of Zorg Instituut Nederland (ZIN), aims to establish the added value of rTMS applied over the pre-supplementary motor area (preSMA) when combined with ERP in OCD patients, who show no/insufficient response to ERP (alone or combined with medication). In case of proven cost-effectiveness it will lead to the addition of rTMS as insured health care for patients with OCD.
Objective: assess the (cost-)effectiveness of 1Hz rTMS to the pre-SMA as adjuvant treatment to ERP in OCD patients who show no/insufficient response to ERP (alone or combined with medication)
Study design: multi-center placebo-controlled double-blind randomized controlled trial with an intervention phase of 5-7 weeks and a follow-up phase of 12 months
Study population: 250 adult (18 years and older) OCD patients who show no/insufficient response to ERP
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •OCD as current primary diagnosis
- •Age 18 and older
- •Yale-Brown Obsessive-Compulsive Scale (YBOCS) score of 16 or higher.
- •Insufficient response to state-of-the art exposure therapy with response prevention (ERP) and/or drop-out from ERP due to extreme anxiety/avoidance
- •The following comorbid disorders are allowed (as long as OCD is the current primary diagnosis): depression, other anxiety disorders, ADHD, tic/Tourette's disorder, eating disorders, personality disorders, autism spectrum disorder (when this does not dominate the clinical profile, i.e. is not main diagnosis).
- •Commitment to actively undergo intensive exposure therapy (both supervised during ERP sessions, as well as unsupervised at home)
- •Unmedicated (for at least 8 weeks) or stable dosage of psychotropic medication (for at least 8 weeks), involving serotonergic antidepressants (SSRI, SNRI, clomipramine). Other psychotropic medication that is allowed (provided dosage is stably established for at least 8 weeks): methylphenidate, mood stabilizers, antipsychotic drugs
- •Ability to participate in frequent treatment sessions (4 days/week, for 5 (or 6, or 7) weeks) at one of the 5 sites nearest to their home and/or work
- •Ability to participate in pre-treatment MRI session (for neuronavigation) at one of the 3 academic sites nearest to their home and/or work
- •Capacity for providing informed consent
排除标准
- •OCD patients with hoarding as main symptom dimension
- •The following comorbid disorders (current diagnosis) are not allowed: psychotic disorders, bipolar disorder, autism spectrum disorder (when this dominates the clinical profile, i.e. is diagnosed as main disorder), substance use disorder
- •Active suicidal thoughts and intent to act on it
- •Chronic use of benzodiazepines is not allowed
- •Cochlear implant
- •(History of) epilepsy
- •Pregnancy
- •Extreme claustrophobia or metallic objects in or on the body, preventing from participation in MRI session
- •Space-occupying lesion on MRI
- •Previous rTMS treatment (for blinding reasons)
研究组 & 干预措施
real rTMS
verum rTMS condition, 1500 continuous 1-Hz pulses to the pre-SMA
干预措施: repetitive transcranial magnetic stimulation (rTMS) (Combination Product)
sham rTMS
sham rTMS condition, 1500 continuous 1-Hz pulses to the pre-SMA
干预措施: repetitive transcranial magnetic stimulation (rTMS) (Combination Product)
结局指标
主要结局
Y-BOCS
时间窗: The primary endpoint is the difference between the active and sham intervention groups in post-treatment severity of OCD, estimated using an ANCOVA model that adjusts for pre-treatment severity of OCD.
The severity of OCD as measured by the Yale-Brown Obsessive-Compulsive Scale Y-BOCS I
次要结局
- Clinical Global Impression (CGI) improvement scale(baseline (T0) versus directly post-treatment (5, 6 or 7 weeks post-baseline, dependent on duration of treatment) + 3, 6 and 12 months follow-up)
- Societal costs, measured through the iMTA Productivity Cost Questionnaire (iPCQ)(baseline (T0) versus directly post-treatment (5, 6 or 7 weeks post-baseline, dependent on duration of treatment) + 6 and 12 months follow-up)
- Societal costs, measured through the iMTA Medical Consumption Questionnaire (iMCQ)(baseline (T0) versus directly post-treatment (5, 6 or 7 weeks post-baseline, dependent on duration of treatment) + 6 and 12 months follow-up)
- response and remission(baseline (T0) versus directly post-treatment (5, 6 or 7 weeks post-baseline, dependent on duration of treatment) + 3, 6 and 12 months follow-up)
- Standard Mean Difference (SMD) on the Clinical Global Impression (CGI) severity scale(baseline (T0) versus directly post-treatment (5, 6 or 7 weeks post-baseline, dependent on duration of treatment) + 3, 6 and 12 months follow-up)
- Tolerability of the treatment and side effects, using an in-house questionnaire(after 1st and last week of treatment)
- Quality of life (EQ-5D-5L)(baseline (T0) versus directly post-treatment (5, 6 or 7 weeks post-baseline, dependent on duration of treatment) + 3, 6 and 12 months follow-up)
- depression, measured through the Beck Depression Inventory(baseline (T0) versus directly post-treatment (5, 6 or 7 weeks post-baseline, dependent on duration of treatment) + 3, 6 and 12 months follow-up)
- anxiety, measured through the Beck Anxiety Inventory(baseline (T0) versus directly post-treatment (5, 6 or 7 weeks post-baseline, dependent on duration of treatment) + 3, 6 and 12 months follow-up)
研究者
O.A. van den Heuvel
prof.dr. (MD PhD)
Amsterdam UMC, location VUmc