PDE4 Inhibition and Theta-burst Stimulation Transcranial Magnetic Stimulation Motor Plasticity: a Randomized Placebo-controlled Single-blind Crossover Study
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Motor evoked potential amplitude
研究概览
简要总结
Repetitive transcranial magnetic stimulation (rTMS) uses a magnetic field to non-invasively induce electrical function within the brain. Stimulation allows brain cells to change the way that they adapt and communicate with each other, known as 'synaptic plasticity'. It is thought that alterations in these adaptive brain changes underlie the ability of rTMS to treat mental illnesses like depression.
The regulation of synaptic plasticity is complex, and involves multiple interacting factors and redundant systems to ensure that plasticity is carefully regulated. To date, studies attempting to alter impact synaptic plasticity have done so using pharmacological adjuncts that target extracellular contributions to plasticity. Here, we propose the first proof of principle study targeting intracellular regulation of plasticity by using a pharmacological adjunct targeting Phosphodiesterase 4 (PDE4), a key regulator a cyclic AMP gradients in brain cells.
We will pair TMS with electromyography (EMG) to measure activity dependent changes in the motor cortex following rTMS to test the ability of a PDE4 inhibition to enhance synaptic plasticity after rTMS.
详细描述
This study will employ a randomized, placebo-controlled single-blind crossover trial of adjunctive roflumilast with intermittent or continuous theta burst (iTBS/cTBS) TMS to the primary motor cortex. Participants will complete a screen visit to determine eligibility based on the inclusion/exclusion criteria. If the participants are not eligible, no further study procedures will be conducted.
Randomization with allocation concealment of eligible patients to begin with either the study medication or placebo arm of the study will involve a random number sequence generated a priori with atmospheric noise, with single-blind random condition assignment and allocation concealment.
Baseline corticospinal excitability will be quantified. One hour following ingestion of the blinded capsule iTBS/cTBS will be applied to the primary motor cortex, and the response will be quantified through a combination of motor evoked potentials (MEPs) at a fixed stimulus intensity, cortical silent period, and a range of stimuli to generate stimulus response curves (SRCs).
The duration of each arm is up to 2.5 hours, and they will be separated by at least 1 week.
All participants will complete a questionnaire to assess any side effects (emotional and physical) following each rTMS session.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy individuals (no chronic medical conditions).
- •Aged 18-60 years.
排除标准
- •Previous stroke
- •Current Renal Disease
- •Current Liver Disease
- •Allergy to roflumilast or any of its non-medicinal ingredients
- •Current psychiatric concerns
- •Currently taking any medications with known serious interactions with roflumilast (abametapir, apalutamide, dabrafenifb, enzalutamide, fexinidazole, idelalisib, ivosidenib, lonadarnib, ritonavir, secobarbital, tucatinib, and voxelotor).Intracranial metallic objects (dental hardware is not an exclusionary criterion)
- •Substance use disorder
- •The inability to refrain from alcohol use for 24 hours prior to stimulation
研究组 & 干预措施
Intermittent Theta-Burst Stimulation with Placebo
Intermittent theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested a placebo.
干预措施: Placebo (Drug)
Intermittent Theta-Burst Stimulation with Placebo
Intermittent theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested a placebo.
干预措施: Intermittent theta-burst stimulation transcranial magnetic stimulation (Device)
Intermittent Theta-Burst Stimulation with Roflumilast
Intermittent theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested roflumilast 500mcg.
干预措施: Roflumilast (Drug)
Intermittent Theta-Burst Stimulation with Roflumilast
Intermittent theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested roflumilast 500mcg.
干预措施: Intermittent theta-burst stimulation transcranial magnetic stimulation (Device)
Continuous Theta-Burst Stimulation with Placebo
Continuous theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested a placebo.
干预措施: Placebo (Drug)
Continuous Theta-Burst Stimulation with Placebo
Continuous theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested a placebo.
干预措施: Continuous theta-burst stimulation transcranial magnetic stimulation (Device)
Continuous Theta-Burst Stimulation with Roflumilast
Continuous theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested roflumilast 500mcg.
干预措施: Roflumilast (Drug)
Continuous Theta-Burst Stimulation with Roflumilast
Continuous theta-burst stimulation delivered to the left primary motor cortex after the participant has ingested roflumilast 500mcg.
干预措施: Continuous theta-burst stimulation transcranial magnetic stimulation (Device)
结局指标
主要结局
Motor evoked potential amplitude
时间窗: -5 minutes, -10minutes, -5 minutes, and immediately prior to theta-burst stimulation, then +5 minutes, +10 minutes, +15 minutes, +20 minutes, +25 minutes, +30 minutes, +45 minutes and +60 minutes after theta-burst stimulation.
Motor evoked potentials will be measured using surface electrodes placed over the first dorsal interosseous muscle of the hand to a single stimulus intensity of 120% of resting motor threshold.
次要结局
- Motor evoked potential stimulus response curve(Baseline, 30 minutes following theta-burst stimulation, 60 minutes following theta-burst stimulation.)
- Cortical silent period(Baseline, 30 minutes following theta-burst stimulation, 60 minutes following theta-burst stimulation.)