An Implantable Pacemaker Optimized for Smooth Muscle Stimulation

描述(申请人提供)：便秘是西方国家2%到27%的人口中的一种常见症状。在美国，每年有250多万人去看医生，92,000人住院，泻药销售额达数亿美元。事实证明，在胃肠道相关的临床应用中，使用电刺激平滑肌的设备特别有用。具体地说，电刺激已被证明在治疗包括胃瘫和肥胖以及最近的慢性便秘等指征方面有效。围绕着平滑肌刺激装置的技术还没有得到优化。这主要可以归因于围绕平滑肌对各种电参数刺激的反应的知识和研究方面的差距。我们第一阶段项目的具体目标是通过实验确定最优的电脉冲波形类型和脉冲持续时间，以实现对平滑肌的能量有效刺激。总而言之，与使用传统的矩形恒流脉冲相比，使用截断的指数两相波形和预先测量的电荷转移时，平均节省了44%的能量。这一第二阶段方案的目标是设计、制造和测试一种用于治疗慢性便秘的能量高效的植入性平滑肌刺激装置。该设备将提供第一阶段研究中确定的最佳电脉冲参数和脉冲形状，以实现最大的能效。然后，将在犬类受试者身上进行一系列结肠运输研究，以证明该设备的安全性和有效性。这项研究的长期目标是设计、制造并商业化一种完全可植入的、FDA批准的、能量高效的平滑肌电刺激设备来治疗慢性便秘。 与公共卫生相关：慢性便秘导致高达27%的美国人生活质量下降，每年与250万次医生就诊和9.2万次住院有关。大多数药物治疗(即泻药)在治疗慢性便秘方面无效。建议的高能效结肠动力起搏器(CMP-1)的上市将有助于提高与慢性便秘相关的生活质量。

DESCRIPTION (provided by applicant): Constipation is a common symptom affecting between 2 percent and 27 percent of the population in Western countries. In the United States, it results in more than 2.5 million visits to physicians, 92,000 hospitalizations, and laxative sales of several hundred million dollars a year. The use of a device to electrically stimulate smooth muscle proves particularly useful in clinical applications associated with the gastrointestinal tract. Specifically, electrical stimulation has been shown to be effective in the treatment of indications including gastroparesis and obesity and more recently, chronic constipation. The technology surrounding smooth muscle stimulation devices has not been optimized. This can primarily be attributed to a gap in knowledge and research surrounding the response of smooth muscle to stimulation with various electrical parameters. The specific aim of our Phase I project was to experimentally determine the optimal electrical pulse waveform type and pulse duration for the energy efficient stimulation of smooth muscle. In summary, the results show an average energy savings of 44% when using truncated exponential biphasic waveforms with pre- measured charge transfer as compared to using traditional rectangular constant current pulses. The objective of this phase II proposal is to design, build, and test an energy efficient implantable smooth muscle stimulation device for the treatment of chronic constipation. The device will deliver the optimal electrical pulse parameters and pulse shape for maximum energy efficiency as determined in the Phase I research. A series of colonic transit studies will then be performed in canine subjects to demonstrate the safety and efficacy of the device. The long-term goal of this research is to design, build, and commercialize a fully implantable, FDA approved, energy efficient smooth muscle electrical stimulation device to treat chronic constipation. PUBLIC HEALTH RELEVANCE: Chronic constipation causes a decreased quality of life in up to 27% of the U.S. population, and is associated with 2.5 million visits to doctors and 92,000 hospitalizations annually. Most pharmaceutical treatments (i.e., laxatives) are not effective in treating chronic constipation. Availability of the proposed energy efficient Colon Motility Pacer (CMP-1) will help to increase the quality of life associated with chronic constipation.