Subacute Effect of Pharmacological Sensory Stimulation of the Oropharynx by Agonists of TRP Receptors in Swallowing Neurophysiology in the Elderly With Oropharyngeal Dysphagia.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 150
- 试验地点
- 2
- 主要终点
- Change in the score of the Penetration Aspiration Scale
研究概览
简要总结
Oropharyngeal sensory impairments are a potential target for treatment of oropharyngeal dysphagia (OD) in older patients. We previously found acute administration of TRP sensory stimulants improved VFS signs and swallow response. We hypothesized that sub-acute administration of TRP pharyngeal sensory stimulants, would improve cortical neuroplasticity and will lead into a faster and stronger swallow response, however desensitization of TRP receptors may occur. Therefore, the aim of the present study was to assess the biomechanical (Videofluoroscopy) and neurophysiological (pharyngeal sensory evoked potentials -PSEPs- and motor-evoked potentials (MEPs)) effect of 2 week treatment with TRP agonists in older patients with OD. Design: 150 older (>70yr) patients with OD will be included in a Randomized Control Trial assessing the effect of oral administration of either: a) capsaicin (TRPV1); b) piperine (TRPV1/TRPA1) c) cinnamaldehyde (TRPA1); d) citric acid (ASIC3); e) capsaicin+citric acid (TRPV1/ASIC3); and f) placebo (Control). Measurements: 1) VFS signs of safety and efficacy of swallow and timing and extent of swallow response; 2) Latency, amplitude and cortical representation of PSEP and MEP; 3) Substance P concentration in saliva by ELISA as a marker of peripheral stimulation. Results from this study might help to develop new and effective pharmacological treatments for older dysphagic patients, from compensation to recovery of swallow function.
详细描述
The project consists of a randomized, double-blind controlled interventional clinical trial (patient and analysis of results) with five treatment arms and a control group (placebo) involving a total of 150 elderly patients with oropharyngeal dysphagia (25 patients per group).
The recruitment of participants for the study will be carried out from the patients referred to the Dysphagia Unit of the Hospital de Mataró for the evaluation of swallowing disorders. The swallowing function of all candidates to be included in the study will be clinically evaluated using the volume-viscosity swallowing test (V-VST). Those patients with signs of impaired safety of swallowing during the examination (cough, decreased O2 saturation greater than 2% or voice change) will be candidates to participate in the study. They will be informed and in case of acceptance a saliva sample will be taken, and a videofluoroscopy (VFS) will be performed. If the patient presents impaired safety of swallow (Penetration aspiration scale higher or equal than 2), the patient will be definitively randomized to one of the branches of intervention and the rest of the explorations will proceed (sensory evoked potentials to pharyngeal electrical stimulation and pharyngeal motor evoked potentials to transcranial magnetic stimulation). After the treatment period a second evaluation of study procedures will be performed.
The treatment will consist of administering 10mL solution of the study product, according to randomization, 3 times a day (before breakfast, lunch and dinner) for 14 consecutive days after inclusion in the study. Treatment selected according our previous studies (Alvarez-Berdugo et al. Neurogastroenterol Motil 2017) are: Capsaicin 10microM, Piperine 150microM, Cinnamaldehyde 756,6microM + zinc 70microM, citric acid 457,5microM (pH=3,5), Capsaicin 10microM + citric acid 457,5microM (pH=3,5). For the control group, placebo product will be administered, which will be the vehicle solution with a more neutral pH.
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
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 70 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •More than 70 years old.
- •Oropharyngeal dysphagia with impaired safety of swallow (penetration aspiration score higher or equal than 2).
- •Patients able to comply with the study protocol.
- •Signature or the written informed consent.
排除标准
- •Previous history of severe gastrointestinal diseases.
- •Epilepsy or previous convulsive crisis episodes.
- •Pacemaker or implanted defibrillator carriers.
- •Cardiopulmonary instability.
- •Oropharyngeal dysphagia of structural cause.
- •Previous history of head and neck surgery.
- •Neurodegenerative disease.
- •Advanced dementia (GDS higher than 5).
- •Gastroesophageal reflux.
- •Taking drugs with effects on dopamine.
- •Neoplasia or active infection.
- •Alcohol, tobacco or drugs dependence.
- •Participate or have participated in another interventionist clinical trial in the 4 weeks prior to inclusion.
结局指标
主要结局
Change in the score of the Penetration Aspiration Scale
时间窗: Baseline versus 2/3 days after the intervention
Differences found in the videofluoroscopy Penetration Aspiration Scale (from 1 (safe swallow) to 8 (silent aspiration)) between treatments and vs. the placebo group.
次要结局
- Oropharyngeal swallow response (laryngeal vestibule opening time)(Baseline versus 2/3 days after the intervention)
- Substance P(Baseline versus 2/3 days after the intervention)
- Impaired safety of swallow(Baseline versus 2/3 days after the intervention)
- Oropharyngeal swallow response (upper esophageal opening time)(Baseline versus 2/3 days after the intervention)
- Impaired efficacy(Baseline versus 2/3 days after the intervention)
- Oropharyngeal swallow response (laryngeal vestibule closure time)(Baseline versus 2/3 days after the intervention)
- Oropharyngeal swallow response (Bolus final velocity)(Baseline versus 2/3 days after the intervention)
- Pharyngeal sensory evoked potentials(Baseline versus 2/3 days after the intervention)
- Pharyngeal motor evoked potentials(Baseline versus 2/3 days after the intervention)
- Sensory threshold(Baseline versus 2/3 days after the intervention)
- Palatability and comfort with the treatment.(Baseline versus 2/3 days after the intervention)
研究者
Pere Clave
Principal Investigator
Hospital de Mataró