Vedolizumab Induction May Prevent Celiac Enteritis After Gluten Challenge in Established Celiac Patients in Histological Remission
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Normal histopathology following induction dosing with vedolizumab after 2 week gluten challange
研究概览
简要总结
Celiac disease (CD) is characterized as an autoimmune disorder whereby gluten (a protein found in wheat, barley, rye, malt) induces an immunological response in genetically susceptible individuals. The prevalence of CD has been estimated to affect 0.5-1% of the population worldwide. Long term sequelae are numerous and include risk of lymphoma, malabsorption leading to weight loss, anemia, multiple vitamin deficiencies, osteoporosis/osteopenia, secondary autoimmunity, etc. (1)
详细描述
Adult subjects with CD will be recruited through our clinic. All patients enrolled will have established CD diagnosed > 6 months. All patients will have history of abnormal MARSH score on initial duodenal biopsy at diagnosis and MARSH 0 on repeat biopsy following a gluten free diet (GFD). All patients will also have positive celiac serologies (anti-TTG, anti-gliadin, etc.) at diagnosis, as well as, positive HLA DQ2/DQ8 genetic profile. At enrollment, all patients will have negative celiac serologies, indicative of serologic remission on a gluten free diet. Female subjects of childbearing potential (does not include those with history of tubal ligation/surgical sterilization, hysterectomy and/or oophorectomy) who are sexually active with a non-sterilized male partners agree to routinely use adequate contraception from signing informed consent, during study process and for an additional 18 weeks after the last dose of vedolizumab. A male subject who is non-sterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing informed consent throughout the duration of the study and for 18 weeks after the last dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- 是
入选标准
- •Patients must meet the following criteria for study entry:
- •Adult patients with Celiac Disease (CD)
- •Without any additional co-morbidities
- •Normal renal and hepatic function
- •Diagnosis of CD established at least 6 months prior to trial with diagnostic serology, genetic profile, endoscopic appearance and histopathology report In histologic and serologic remission (defined as MARSH 0 and negative anti-tissue transglutaminase, etc.) following a gluten free diet
- •Naïve to treatment with vedolizumab
- •Able and willing to provide written informed consent
- •Eligibility criteria for laboratory profiles - healthy patient normal laboratory reference values
- •WBC 4.5-12.0 k/UL
- •Platelet count- 140-415 k/UL
- •Hemoglobin- 11.0-17.4 %g/dL
- •Renal Function-
- •Creatinine- 0.5-1.3 mg/dL
- •BUN- 5-20 mg/dL
- •Hepatic Function
- •Albumin - 3.3-5.0 g/dL
- •INR- 0.9-1.1
- •AST- 0-37 U/L
- •ALT- 0-40 U/L
- •Total Bilirubin- 0.1-1.3 mg/dL
- •Alk Phos- 35-150 U/L
排除标准
- •Patients who meet any of the following criteria will be excluded from study entry:
- •Abnormal MARSH score on enrollment histopathology
- •Elevated celiac serologies (anti-tissue transglutaminase, etc.)
- •Current use of biologics or immunomodulators Adalimumab, infliximab, Ustekinumab, Golimumab, Tocilizumab, Certolizumab, Etanercept, Rituximab, Anakinra, Abatacept, Tofacitinib, Methotrexate, Azathioprine, 6-MP.
- •Current use of immunosuppressive therapy including intermittent systemic corticosteroids within two months of vedolizumab induction
- •History of intestinal lymphoma (MALToma, etc.)
- •History of cancer including hematologic malignancy, solid tumors, carcinoma in situ, etc.
- •Pregnant or lactating
- •Fertile females will require at least one form of birth control
- •Lack of peripheral venous access
- •Inability to comply with study protocol, in the opinion of the investigator
- •Neurological conditions which may interfere with monitoring for PML
- •History of demyelinating disease or history of major neurological disease
- •History of alcohol, drug or chemical abuse < 6 months prior to screening
- •History of active tuberculosis (TB) or a positive screening test for latent mycobacterium tuberculosis infection
- •Positive PPD= > 10 mm or > 5mm in patients on 15 mg or more of prednisone
- •History of BCG vaccination should be screened using Quantiferon TB Gold test
- •An Indeterminate Quantiferon test will require a chest X-ray to rule out active TB and consultation with an infectious disease specialist to confirm the risk of latent
- •TB is low and that patients can be safely enrolled in the trial
- •History of recurrent opportunistic infections and/or of severe or disseminated viral infections
- •Active autoimmune disease
- •Active inflammatory bowel disease
研究组 & 干预措施
Vedolizumab
Vedolizumab (Entyvio) 300mg IV at week 0, 2 and 6
干预措施: Vedolizumab (Drug)
结局指标
主要结局
Normal histopathology following induction dosing with vedolizumab after 2 week gluten challange
时间窗: 12 weeks
Remission is defined in this study as negative celiac antibodies and normal duodenal biopsies
Normal histopathology following induction dosing with vedolizumab
时间窗: 12 weeks
Remission is defined in this study of negative celiac antibodies and normal duodenal biopsies
次要结局
未报告次要终点
研究者
Barry Kaufman, MD
Director of Clinical Research
AGA Clinical Research Associates, LLC