Effects of Type A Botulinum Toxin in Obstructed Defecation Syndrome: a Phase II Randomized, Parallel-Group, Triple-Blind, Placebo-Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Changes in the Altomare Obstructed Defecation Syndrome- Score (ODS-S) and Patient Assessment of Constipation- Quality of Life Score (PAC-QoL)
研究概览
简要总结
The purpose of this study is to determine if Botulinum Toxin-A (Botox) injection will improve symptoms of constipation in obstructed defecation syndrome (ODS).
详细描述
Constipation represents one of the five most common physician diagnoses for gut disorders. Obstructed defecation syndrome (ODS) is an under-treated condition which accounts for 30%- 50% of all patients with constipation and it is more common as people age. ODS is due to the abnormal contraction of the puborectalis muscle (a muscle around the anus that should relax during defecation).
Biofeedback therapy and medical management are the standards of care for ODS. Typically patients are first managed with dietary modifications (fiber supplementation, increased fluids) and medication (laxatives, enemas). If constipation is not improved, they will undergo biofeedback, which lasts from 3-8 sessions on average. Biofeedback acts on the cause of ODS and it has good short-term success, but around 50%-70% of treated patients re-experience constipation after one year. The main drawbacks of biofeedback for ODS are the facts that it is expensive, time-consuming, available in few select-centers and its success depends very much on the provider. Biofeedback is delivered in multiple 1-hour clinic sessions, so many patients don't finish all recommended sessions and their constipation may recur faster.
Botox also acts on the cause of ODS and was shown to improve constipation within 1-3 weeks after the injection. Botox is delivered as a one-time injection in the puborectalis muscle and external anal sphincter (the muscle right around the anus). The injection can be performed in the clinic under local anesthesia, and the patient goes home afterwards. Currently, Botox is used for treatment of patients who fail biofeedback and medical management, to avoid the options of last resort (resection of the colon with stoma). To this day, no adequately designed study has confirmed that Botox is indeed superior to placebo (normal saline) for the treatment of ODS. The results from this study will provide valuable data on the ability of Botox to improve symptoms of constipation and the duration of its effect. This project has the potential to increase the availability of effective treatments for ODS.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females 18 years or older of all races and backgrounds
- •Competent to give informed consent
- •Meet the Rome III diagnostic criteria for functional constipation
- •Inability to relax the puborectalis muscle at electromyography
- •Altomare Obstructed Defecation Syndrome score of 15 points or above
- •Failure of treatment with 2 conservative measures which may be as follows:
- •1 laxative (osmotic or stimulant) for 2 weeks
- •1 fiber supplement for one month
- •And/or trial of biofeedback for at least 4 sessions
排除标准
- •Previous treatment with Botox (possible antibodies)
- •Known hypersensitivity to any of the components of the toxin
- •Medication regimen includes narcotics
- •Previous radiation therapy to the anal canal and rectum
- •Prior proctectomy
- •Presence of unhealed and symptomatic anal fissure
- •Presence of anal pain
- •Presence of fecal incontinence
- •Presence of full thickness rectal prolapse
- •Presence of internal sphincter myopathy
- •Inflammatory bowel disease or proctitis
- •Pregnancy or breast-feeding
- •Subject is currently enrolled/ just finished participating in a clinical trial in which the intervention/ its carry-over effect may interact with the intervention in this trial
研究组 & 干预措施
Normal saline
Patients will receive normal saline (placebo) injected in the puborectalis muscle and external anal sphincter.
干预措施: Normal Saline (Drug)
Botulinum Toxin-A
Patients will receive Botulinum Toxin-A (Botox) injected in the puborectalis muscle and external anal sphincter. We will use 100 units of Botox, a dose with a good safety profile that has been proven to work in previous studies performed in adults.
干预措施: Botulinum Toxin-A (Drug)
结局指标
主要结局
Changes in the Altomare Obstructed Defecation Syndrome- Score (ODS-S) and Patient Assessment of Constipation- Quality of Life Score (PAC-QoL)
时间窗: Baseline, 1 month after injection
The primary outcome measure will be the change from baseline in the sum of ODS-S and PAC-QoL at 1 month after the Botox injection. This measures the symptomatic improvement in ODS. ODS (altomare obstructed defecation syndrome score) scores range from 0 (minimum) to 31 (maximum) where 31 is the most severe (worse outcome) and 0 is no symptoms (better outcome). The scale for PAC-QoL (Patient Assessment of Constipation- Quality of life score) is a minimum of 0 and a maximum of 112 where 0 is highest quality of life (better outcome) and 112 is lowest quality of life (worse outcome) Larger number for change would suggest a better outcome
次要结局
- Changes in the Patient Assessment of Constipation- Quality of Life Score (PAC-QoL)(Assessed at baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months)
- Relaxation of Puborectalis With Push Measured by EMG(Baseline, 1 month follow-up visit)
- Success of Balloon Expulsion Test(Baseline, 1 month follow-up visit)
- Changes in Health-Related Quality of Life(Baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months)
- Changes in Fecal Incontinence Quality of Life Scale (FIQoL)(Assessed at baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months)
- Change in Anal Sphincter Function(Baseline, 1 month follow-up visit)
- Change in Defecation Index(Baseline, 1 month follow-up visit)
- Changes in the Altomare ODS Score (ODS-S)(Assessed at baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months)
- Changes in Cleveland Clinic Fecal Incontinence Score (CCFI)(Assessed at baseline, 1, 3, 6 and 12 months after injection and value compared from baseline to 12 months)
研究者
Liliana Bordeianou
Assistant Professor of Surgery, Division of General and Gastrointestinal Surgery
Massachusetts General Hospital