Treatment Effect of Colesevelam for Bile Acid Diarrhoea - a Randomised Placebo-controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 255
- 试验地点
- 4
- 主要终点
- Intention-to-treat diarrhoea remission rate defined by the Hjortswang criteria for colesevelam in patients with BAD defined by C4 > 46 ng/mL
研究概览
简要总结
Bile acid diarrhoea is a chronic disease that impairs quality of life. One in 100 has the condition and many suffer from the disease without knowing. The current test is called SeHCAT and is expensive and time-consuming and is unavailable in many places, including the US. The disease is often misdiagnosed as irritable bowel syndrome and estimated one third of patients with irritable bowel syndrome of the mixed type and the diarrhoea predominant type suffer from bile acid diarrhoea without knowing.
A blood test called 7α-hydroxy-4-cholestene-3-one (C4) could make it much easier to diagnose bile acid diarrhoea.
To establish the new test, the results of both C4 and SeHCAT are compared with the treatment effect of the drug called colesevelam.
We invite patients who are referred for the SeHCAT test to participate in the trial. The SeHCAT test takes two days that are one week apart. The study patients register stool habits with a diary in the week between the SeHCAT visits. Based on the diary results, we screen for eligibility; e.g. a certain degree/severity of diarrhoea is required for participation. We treat eligible study patients (i.e those with diarrhoea) with either colesevelam or placebo (medicine without effect) that is randomly assigned. 170 study patients need to complete the treatment.
We aim to validate (ie. compare) both the C4-test and the SeHCAT test with the colesevelam treatment response as the reference.
详细描述
ISSUE Bile Acid Diarrhoea (BAD) affects 1% of the general population and many people live with the disease and the impaired quality of life it causes without knowing it. The current scintigraphic seleno-homo-taurocholic acid retention test (SeHCAT) is time-consuming, expensive and causes a diagnostic bottleneck. the SeHCAT test is unavailable in many countries including the US. The biomarker 7α-hydroxy-4-cholesten-3-one (C4) could provide a cheap and available diagnostic option to surmount the issue of the many undiagnosed patients. The pivotal step for this is validation of the C4-test with the placebo-controlled treatment effect.
PURPOSE
- To determine the efficacy and safety of colesevelam for treating Bile Acid Diarrhoea
and 2. 2. To correlate both the current scintigraphic 75-Selenium conjugated Tauro-homocholic acid retention test (SeHCAT) and the biochemical marker of BAD 7alpha-hydroxy-4-cholesten-3-one (C4) with colesevelam treatment response, and to validate the cut-off values determined in the 'VABAD' trial
BACKGROUND Chronic diarrhoea affects 4-5% of the Western adult population and often results in specialist referral and endoscopies. Availability of the diagnostic SeHCAT test for BAD is limited, and BAD is often mistaken for the Irritable Bowel Syndrome (IBS). 32% of patients with two of the three IBS subtypes have BAD and the prevalence of BAD in the general population is thus approximately 1%.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Study subjects and all investigators are blinded. As effect and side effects of the active drug may demask the blinding, a central study nurse is the primary contact for the subjects during the intervention periode regarding everything except suspected/possible serious events.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient referred to Clinical Physiological/Nuclear Medicine departments for SeHCAT
- •Suspected Bile acid diarrhoea
- •Age > 18 years and under 80 years
- •women of fertile age must use safe contraception during the treatment part of the study
- •Ability to give informed consent after written and oral information in Danish language
排除标准
- •Inflammatory bowel disease, including microscopic colitis
- •Investigator assessed debilitating chronic disease e.g. World Health Organisation performance score 3-5
- •Prior treatment with colesevelam
- •Treatment with laxatives or anti-diarrhoeal drugs during the study
- •Except for stable dose the last four weeks of psyllium husk and opioids for pain
- •Breastfeeding women
- •Crucial medication that cannot be separated appropriately from colesevelam
- •i.e. taken one hour before or 4 hours after colesevelam
- •Oral anticoagulation, both warfarin, and new oral anticoagulation
- •Treatment with cyclosporine within two months
- •Bowel obstruction (subileus or ileus)
- •Biliary obstruction
- •Short bowel syndrome
- •Bowel ostomy
- •Allergy to colesevelam or its constituents
- •Allergy to placebo constituents (excluding lactose)
- •Investigator assessed high risk of non-compliance
- •If on statin/fibrate medication, unwilling to pause medication between study visits 1 and 2
研究组 & 干预措施
Colesevelam, active arm
Colesevelam hydrochloride, 625mg tablets. Overencapsulated with DB caps AAA for blinding.
Oral use. Dose: 1, 2, or 3 capsules twice daily. Starting dose 2 capsules twice daily. Dose titration by specific criteria by a central study nurse Treatment duration 12 days
干预措施: Colesevelam Hydrochloride (Drug)
Placebo
Inactive placebo tablets. Overencapsulated with DB caps AAA for blinding. Oral use. Dosage and treatment duration as specified for colesevelam
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Intention-to-treat diarrhoea remission rate defined by the Hjortswang criteria for colesevelam in patients with BAD defined by C4 > 46 ng/mL
时间窗: Intervention days 6 through 12 (last seven intervention days)
drop-outs are set as treatment failures in the ITT analysis if less than five of the last seven treatment days that comprise the endpoint assessment period are complete. If five or more of these days are complete, a mean of these days will be used for calculating the Hjortswang response criterium. We will fit an appropriate generalized linear mixed-effects model with an unstructured covariance pattern of the chance of response with colesevelam versus placebo. In addition, baseline adjustments for the severity of diarrhoea (mean per day sum of Bristol type 6 and 7 stools) and the severity of bile acid malabsorption (visit 2 C4 value) will be made
次要结局
- Per protocol diarrhoea remission rate defined by the Hjortswang criteria for colesevelam in patients with BAD defined by C4 > 46 ng/mL(Intervention days 6 through 12 (last seven intervention days))
- placebo-controlled effect of colesevelam in patients with bile acid diarrhoea defined by C4 >46 ng/mL on the absolute number of stools as mean per day over 6 or 7 days(Baseline period compared with Intervention days 6 through 12 (last seven intervention days))
- Intention-to-treat diarrhoea remission rate defined by the Hjortswang criteria for colesevelam in patients with BAD defined by SeHCAT <= 10%(Intervention days 6 through 12 (last seven intervention days))
- Per protocol diarrhoea remission rate defined by the Hjortswang criteria for colesevelam in patients with BAD defined by SeHCAT <= 10%(Intervention days 6 through 12 (last seven intervention days))
- The de facto effectiveness of colesevelam on health related quality of life assessed as the sum of Short Health Scale scores(Baseline period compared with Intervention days 6 through 12 (last seven intervention days))
- placebo-controlled effect of colesevelam in patients with bile acid diarrhoea defined by C4 >46 ng/mL on the total number of Bristol type 6 and 7 stools as a mean over 6 or 7 days(Baseline period compared with Intervention days 6 through 12 (last seven intervention days))
研究者
Lars Kristian Munck
Senior Physician, Clinical Associate Professor, Sponsor-Investigator
Zealand University Hospital