A Single-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of 3,3'-Diindolylmethane (BR-DIM) in Patients With Systemic Lupus Erythematosus (SLE)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 主要终点
- Autoantibody Production
研究概览
简要总结
This is a single center study of patients with inactive or mild SLE being performed to determine the safety, tolerability, and pharmacodynamics of DIM.
详细描述
This study is a single-blinded, placebo-controlled trial to determine the effects of DIM supplementation in patients with SLE. The DIM supplement to be used is BioResponse-DIM® (BR-DIM®), an absorption-enhanced formulation of proven bioavailability in animal testing and human trials. A total of 30 individuals will be enrolled into this 14-month study. Ten patients will be randomly assigned to the Low Dose Group [a daily dose of 225 mg of DIM from BR-DIM]. Ten patients will be randomly assigned to the High Dose Group [a daily dose of 375 mg of DIM from BR-DIM]. Ten patients will be randomly assigned to a matching placebo group, where 5 of these patients will receive matched placebo capsules equaling use in the Low Dose active group, and 5 will receive matched placebo equaling use in the High Dose active group. Each active capsule will deliver 75 mg of DIM from BR-DIM. Dosing will span 52 weeks. BR-DIM or comparably packaged placebo will be administered orally with meals twice per day. Placebo subjects randomized to the Low Dose group will take 2 placebo capsules in the am and 1 capsule in the pm and placebo subjects randomized to the high dose group will take 3 capsules in the am and 2 capsules in the pm. Low Dose active subjects will take 2 capsules in the am and 1 capsule in the pm. High Dose active subjects will take 3 capsules in the am and 2 capsules in the pm. Study subjects will be randomly assigned to one of the four treatment groups. Randomization procedures will be overseen by the staff of the North Shore Long Island Jewish General Clinical Research Center. The randomization schedule will be set up by the Bio-Statistics unit. The Investigator will contact the Research Pharmacy at North Shore University Hospital who will contact the Bio-Statistics unit once the subject signs the Informed Consent Form in order to learn which treatment regimen the subject is assigned to. Patients and control subjects will be given the appropriate amount of study medication at each visit to take home with them. Study personnel will monitor compliance by asking the patient to return any unused study medication at each visit for drug accountability. In addition, medication logs will be kept by the study subject and will be presented to the study coordinator at each visit. The subject, but not study personnel, will be blinded to the study drug assignments.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Stable SLE disease activity for a period of at least 2 months prior to the Screening visit, based on the clinical judgment of the investigators
- •History of measurable anti-dsDNA, anti-Sm, RNP, SS-A (anti-Ro), or SS-B (anti-La) autoantibodies
- •Age > 18 and < 50
- •Ability to understand the requirements of the study, provide written consent, and comply with the study protocol procedures
- •A negative pregnancy test
- •The use of contraception by fertile females
- •A serum creatinine <1.8 mg/dL
- •Serum hepatic transaminases < 1.25 times the upper limits of normal
- •Hemoglobin > 9.5, WBC > 3.0, neutrophils > 1.2; platelets > 90,000
排除标准
- •Immunosuppressive therapy (e.g. cyclophosphamide, cyclosporine, azathioprine, mycophenolate mofetil) or intravenous gamma globulin within 6 months of study entry
- •Prior receipt of biologic agents, unless 9 months or 4 half-lives, whichever is greater, have passed since the last dose
- •Prednisone > 10 mg/day (or its pharmacologic equivalent) within 2 months of randomization
- •Pregnancy or the intent to conceive during the study or 3 months after study completion
- •Concurrent medications such as danazol, DHEA, or other medications that affect estrogen levels or metabolism
- •Nursing mothers
- •Oral contraceptive use
- •The presence of infection
- •A history of poor procedural compliance
- •Receipt of an investigational drug within 60 days of baseline
- •Malignancy (except for basal cell carcinoma)
- •Dose changes of steroids, anti-malarial drugs, or NSAID's within 4 weeks of randomization
- •Peri- or post-menopausal state
- •History of clinical evidence of active significant acute or chronic diseases (i.e., cardiovascular, pulmonary, untreated hypertension, anemia, gastrointestinal, hepatic, renal, neurological, cancer, or infectious diseases) that could confound the results of the study or put the subject at undue risk
- •History of any other medical disease, laboratory abnormalities, or conditions that would make the subject (in the opinion of the investigators) unsuitable for the study
- •Current drug or alcohol addiction
研究组 & 干预措施
Low Dose
10 patients 225 mg of BR-DIM. 2 capsules AM and 1 PM. 52 weeks duration.
干预措施: BR-DIM (Drug)
High Dose
10 patients 375 mg of BR-DIM. 3 capsules AM and 2 PM. 52 weeks duration.
干预措施: BR-DIM (Drug)
Placebo
10 patients receiving weight matched placebo. 5 for high dose and 5 for low dose. 52 weeks of weight matched pills.
干预措施: Placebo (Drug)
结局指标
主要结局
Autoantibody Production
时间窗: 14 Months
Routine lab testing to determine whether DIM supplementation will decrease autoantibody production
Safety and Tolerability Routine clinical and laboratory parameters as well as SLE activity measurement with SELENA Systemic Lupus Erythematosus Disease Activity Index assessment.
时间窗: 14 months
Routine clinical and laboratory parameters as well as SLE activity measurement with SELENA Systemic Lupus Erythematosus Disease Activity Index assessment.
Estradiol Hydroxylation Pathways
时间窗: 14 months
Measure alterations in the ratio of 2-hydroxyestrone/ 16alpha-hydroxyestrone (2-OHE/16alpha-OHE) in the urine.
T and B Lymphocytes
时间窗: 14 Months
Qualitative and quantitative abnormalities in B- and T-lymphocytes abound in human SLE. In this aim, phenotypic analyses of B- and T-lymphocyte subsets as well as functional analyses will be ascertained in order to evaluate the effects of DIM on these parameters.
次要结局
未报告次要终点