Peripheral TMD Pain Mechanisms and the Effect by Botulinum Toxin A. A Randomized, Controlled, Double-blind Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Change of gene expression measured with bulk RNA-seq
研究概览
简要总结
The goal of this clinical trial is to investigate the effect of botulinum toxin on neurons' plasticity in the masseter muscle in humans with and without painful myogenous temporomandibular disorders (TMDM). The main questions it aims to answer are:
- does treatment with botulinum toxin alter gene expressions, epigenetic signatures, and cells plasticity in the masseter muscles of TMDM patients?
- do any such changes differ between patients with local and regional TMDM?
- does treatment with botulinum toxin influence pain characteristics (intensity, frequency, and sensibility) and other variables in patients with TMDM and are there correlations between significantly changed expression of biomarkers and other variables?
Participants will be examined with a questionnaire, clinical examination (including quantitative sensory testing; QST), and microbiopsy sampling from one of the masseter (MM) and anterior tibialis (AT) muscles and are then randomized to treatment with botulinum toxin or control (isotonic saline). Follow-ups occur after one and three months for all patients, and six months with questionnaire, clinical examination, and collection of post-treatment microbiopsies to see if botulinum toxin alter peripheral molecular events and clinical variables.
详细描述
Patient recruitment:
The patients will be recruited among those referred to the Specialist Clinic for Orofacial Pain and Jaw Function at the University Dental Clinic, Karolinska Institutet, Huddinge, Sweden, or via advertisement.
Randomization:
Patients will be randomly assigned to treatment by a random generator (www.randomization.com). For each participant the treatment will be written on a note and placed in a sealed envelope by a researcher not involved in any other part of data collection. A second person not involved in patient examination will open the envelope, prepare the syringe with the randomized solution, and place it in the examination room before the examiner and patient enters it. Botulinum toxin and saline have identical appearance so the participant and investigator will be masked to treatment assignment.
Procedure:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •a diagnosis of TMDM myalgia or myofascial pain according to the DC/TMD criteria
- •females with adequate contraceptives and a negative pregnancy test
- •pain upon digital palpation of at least one of the masseter muscle
- •a characteristic pain intensity of > 40/100
- •a negative pregnancy test at the day of treatment
排除标准
- •difficulties understanding the Swedish language
- •systemic inflammatory connective tissue diseases
- •widespread pain
- •neuromuscular disorders
- •diagnosed or severe psychiatric disease
- •neuropathic pain
- •pain of dental origin
- •history of trauma to the face, head or neck
- •pregnancy or nursing
- •known allergy to botulinum toxin or antibiotics
- •use of muscle relaxants, antidepressant, neuropsychiatric, anticoagulant drugs, or aminoglycoside antibiotics
- •previous treatment with botulinum toxin during the last 12 months
- •use of analgesic or anti-inflammatory medication during the 48 hours preceding biopsy
- •skin infection over injection/biopsy site
研究组 & 干预措施
Isotonic saline
Single injection of 1 mL isotonic saline (0.9 mg/mL) into the same five points per side in a similar manner as for botulinum toxin.
干预措施: Isotonic saline 0,9% (Drug)
Botulinum toxin
Single bilateral injection into three standardized points of the masseter muscles and two of the anterior temporalis muscle. The total dose administered is 100 U (10 U/point) which is dissolved in 1 mL of isotonic saline. Thus, 0.1 ml of botulinum toxin solution is injected in each point.
干预措施: Botulinum toxin type A (Drug)
结局指标
主要结局
Change of gene expression measured with bulk RNA-seq
时间窗: 1-6 months
Gene expression in the anterior tibialis muscle (internal control) will be subtracted from the masseter and the patients will then be clustered according to DEGs and compared to baseline.
Change of proteome measured with affinity-based proteomics.
时间窗: 1-6 months
The protein expression will be measured with affinity proteomics using Olink platforms will be done, which enables analysis of several hundreds of proteins in one analysis
Change of RNA expression measured with single-cell RNA (scRNA) seq/spatial trnascriptomics.
时间窗: 1-6 months
ScRNA-seq will be analyzed by SEURAT
Change of expression of sensory neuron markers measured with IHC
时间窗: 1-6 months
The expression will be measured as the change of frequency (%) of selected sensory neuron markers.
Change of proteome measured with proteomics
时间窗: 1-6 months
The expression wil be measured with two-dimensional gel electrophoresis, followed by liquid chromatography-tandem mass spectrometry and protein network analyses.
次要结局
- Change of pain intensity compared to baseline using 0-10 numeric rating scales (NRS)(1-3 months)
- Global improvement using Patient Global Impression of Change Scale (PGIC)(1-3 months)
- Change of pain quality compared to baseline using the McGill Pain questionnaire (MPQ)(1-3 months)
- Number of participants with adverse events assessed with questionnaire(1-3 months)
- Change of physical function assessed with questionnaire(1-3 months)
- Change of emotional function assessed with questionnaire(1-3 months)
- Number of participants with adverse events assessed with questionnaire(1 week)
研究者
Malin Ernberg
Professor
Karolinska Institutet