Randomized Multicenter International Study to Investigate the Safety and Efficacy of Propionyl-L-Carnitine Hydrochloride Modified Release Tablets in Patients Affected by Mild Ulcerative Colitis Under Oral Stable Treatment
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 147
- 试验地点
- 58
- 主要终点
- Proportion of clinical/endoscopic remissions
研究概览
简要总结
The aim of the trial is to test safety, tolerability and efficacy of Propionyl-L-carnitine modified release tablets 1g/die in reducing the symptoms of the disease with respect to the proportion of patients with disease remission at the end of the 8 weeks of treatment. It will also aim to investigate capability of the treatment in the maintenance of remission after four weeks of treatment interruption; histological changes will be also evaluated and finally, improvement in the overall quality of life as measured by the Short Inflammatory Bowel Disease Questionnaire (SIBDQ)will be investigated.
详细描述
Although it seems clear that an abnormal function of the colonic epithelium is the central problem causing inflammation and the unusual immunological response to the normal gut flora in inflammatory bowel disease (IBD), the actual causes of these dysfunctions are still unknown.
Short Chain Fatty Acids (SCFA) are the main fuel of the colonic epithelium, and are normally produced by the bacterial flora by fermentation of the complex carbohydrates forming non soluble fibers usually introduced with everyday diet. Butyrate alone contributes 70% of the normal colonocyte energy.
Studies done using animal models and colonic mucosa biopsies from patients suffering form ulcerative colitis (UC) have consistently shown that a metabolic change occurs in diseased colonic mucosa, with an impairment of butyrate oxidation (and of beta-oxidation) and an energy shortage that is only incompletely compensated by oxidation of glucose and other substrates such as glutamine.
It is also well known that matrix metalloproteases production is highly increased in IBD and that serum transglutaminase activity is significantly reduced in patients with IBD.
Transglutaminases are enzymes contributing to the crosslinking of matrix proteins and the reduction seen in patients affected by IBD correlates well with the endoscopic and histopathologic grading in UC, meaning that part of the circulating enzyme is sequestered in the injured colonic tissue in the effort to re-build the extracellular matrix during the healing process.
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)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have read the Information for the Patient and signed the Informed Consent Form.
- •Diagnosis of active ulcerative colitis since at least 4 weeks as confirmed endoscopically and histologically.
- •Disease Activity Index comprised between 3 and 6, inclusive (mild ulcerative colitis), with rectal bleeding sub-score of at least
- •Stable background oral aminosalicylates (mesalazine, balsalazide, olsalazine) or sulfasalazine standard therapy for greater than or equal to 4 weeks prior to screening assessments.
- •If female, not pregnant or nursing. For women of childbearing potential, willingness to avoid a pregnancy during the treatment period and for at least 4 weeks from the last dose of drug and utilization of an efficient method of birth control for the entire duration of the trial and until the first menses after a 30-day period after the last dose of trial medication.
排除标准
- •Crohn's disease and indeterminate colitis.
- •Current or previous (in the last 10 days preceding the screening) use of systemic corticosteroids.
- •Use of systemic antibiotics in the last 10 days preceding the screening.
- •Use of systemic Nonsteroidal anti-inflammatory drugs on a repeat basis in the last 10 days preceding the screening.
- •Use of probiotics started within 10 days preceding the screening. A stable regimen from at least 10 days prior to screening is allowed but the patient must be willing to continue up to the end of the study.
- •Use of immunosuppressants or biological agents within the last 6 weeks preceding the screening.
- •Treatment with L-carnitine or its esters derivatives within the last 3 months.
- •Stool culture positive for enteric pathogens (eg, Shigella, Salmonella, Yersinia, Campylobacter) or toxins (C.difficile).
- •Significantly impaired liver, renal, pulmonary or cardiovascular function as assessed by the investigator.
- •History of colon resection.
- •Diverticulitis, symptomatic diverticulosis.
- •Active peptic ulcer disease.
- •Proctitis (extent of inflammation <15 cm from the anus).
- •Bleeding disorders
- •Rectal therapy with any therapeutic enemas or suppositories with the exception of those required for endoscopy during the 10 days preceding the screening.
- •Active or chronic infection(s) or malignancies.
- •Known hypersensitivity to the active ingredient and excipients of the study drug.
研究组 & 干预措施
Propionyl-L-carnitine
modified release tablets 500 mg
干预措施: Propionyl-L-Carnitine (Drug)
Placebo
Modified release tablet 500 mg
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of clinical/endoscopic remissions
时间窗: End of treatment (week 8)
Remission will be defined according with the overall modified Mayo score (Disease Activity Index). A score ≤ 2 with rectal bleeding sub-score = 0 and no other individual sub-score \>1 will be considered necessary to classify the patient in remission state.
次要结局
- Change from baseline in Rectal bleeding evaluation(At week 2, 6 and 8 of treatment and after 4 week follow-up)
- Change from baseline in stool frequency evaluation(At week 2, 6 and 8 of treatment and after 4 week follow-up)
- Change from baseline in C-reactive protein (CRP) and Fibrinogen(End of the treatment (week 8) and after 4 week follow-up)
- Improvement of patients quality of life(End of treatment period (week8) and after 4 week follow-up)
- Haematology(Baseline and end of treatment (week8))
- Electrocardiogram(At baseline and at the end of treatment period (week8))
- Adverse Events collection(8 weeks)
- Serum Chemistry(At baseline and at the end of treatment period (week8))
- Histological response to the treatment(End of treatment (week 8))