A Double-blinded, Randomized Controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of N1, N3-bis-(2-Mercaptoethyl) Isophthalamide (NBMI) in the Reduction of Mercury Levels, in Subjects Exposed to Mercury in Colombia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 116
- 试验地点
- 1
- 主要终点
- Measure the "Change in the subject's urine mercury levels"
研究概览
简要总结
NBMI (N1, N3-Bis-(2-Mercaptoethyl) Isophthalamide) is a new metal chelator drug proposed as an alternative to the current chelators, and it is widely different; compared to the current chelators, consisting of two cysteamine molecules coupled to a single molecule of dicarboxybenzoate. It is used as a chelating agent and has the designation of an orphan drug, in the EU and USA; in the EU it is used for the treatment of mercury toxicity. It is freely soluble in solutions of dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and sodium hydroxide diluted NaOH, slightly soluble in methanol and acetone, and insoluble in water. Pre-clinical data indicates low to no toxicity, and that it reduces the toxicity associated with acute exposure to Hg2+.
No other chelator has been reported to prevent acute mercury toxicity with only one exposure to the chelator. It has the ability to penetrate cell membranes and cross the blood-brain barrier and chelate Hg2+ in a complex that eliminates the availability of Hg2+ and essentially eliminates toxic effects. The antioxidant properties of NBMI could also reduce the toxicity levels of hydroxyl free radicals immediately, upon entering cells suffering from oxidative stress. It is possible that the combined chelation of Hg2+ and the elimination of hydroxyl free radicals contribute significantly to the protective effects observed with the NBMI.
Previous clinical studies conducted in subjects of the Phase I and Phase II a studies conducted, did not show significant adverse events in patients intoxicated with mercury, all patients who received the study medication have tolerated it well, with only mild or moderate adverse events reported; None of these were considered related to the pharmacological treatment of the study. In addition, there is no potential identified with safety problems in laboratory tests, or vital signs evaluations.
The purpose of this Controlled Single-Center Double-Blind Crossover Clinical Trial Phase II b is to determine the efficacy, safety and tolerability of a 14 day 600mg / day of NBMI (N1, N2-bis-2-mercaptoethyl isophthalamide) Treatment, in the reduction of urinary mercury levels versus placebo, in accidentally exposed subjects to mercury in Colombia.
详细描述
This is a Controlled Single-Center Double-Blind Crossover Clinical Trial Phase II b conducted in subjects with a history of chronic exposure to mercury in Colombia.
One hundred and sixteen patients (116) will be randomized in a 1:1 ratio, to either one of the two arms of this trial:
Group A:
NBMI (study drug) with an oral dose of 600 mg corresponding to 6 capsules of 100 mg of NBMI every 24 hours for 14 days.
Group B:
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
The research center must assign an unblinded pharmacist or a designated person and a non-blinded CRO monitor, to monitor medication supply and other unblinded documentation of the study.
Masking through identical capsules and blister in the two arms of intervention.
入排标准
- 年龄范围
- 14 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients with a history of exposure to sources of mercury release by a known event of direct contact with metallic mercury.
- •All subjects must have signed and dated an informed consent / assent consent form approved by the IRB in accordance with regulatory and institutional guidelines. This form must be obtained before performing any procedure related to the protocol that is not part of the subject's normal regimen.
- •Under age minors must also have a psychological evaluation and documentation of Assent added to the Informed Consent Form.
- •Patients with detectable urinary mercury levels >10 ug / L at the time of screening.
- •Patients must be willing and able to comply with clinic visits and all study-related procedures.
- •Subjects with no previous chelation treatment or who have stopped receiving chelation treatment for more than 3 months will be enrolled.
- •Participants must have controlled mercury levels, with no severe clinical manifestations, regardless of what the medical treatment may have been.
排除标准
- •A history of known or suspected hypersensitivity or idiosyncratic reactions to the medication or test excipients. Patients with sulfa-drug sensitivity should be excluded from this study.
- •Levels of mercury in urine / blood at the time of baseline measurement that are below detection threshold.
- •Known history of drug addiction and / or alcoholism.
- •Patients with a known medical condition that, in the opinion of the investigator, could increase the risk associated with participation in the study or with the administration of the study medication (s) under blinded conditions or interfere with the interpretation of the security results.
- •Patients with major surgery or significant traumatic injury who have not recovered at least 14 days before the first dose of the study medications (s) under blind.
- •Subjects with a condition requiring systemic corticosteroid therapy (> 10 mg daily of prednisone equivalent) or other immunosuppressive medications within 14 days before or during treatment are excluded.
- •Women with positive pregnancy test (urine sample) at the time of screening; or women who are breastfeeding, or are of childbearing age who disagree with taking contraceptives during treatment and until Day 28 after the last dose.
研究组 & 干预措施
Arm A: NBMI (Study Medication)
600mg / day N1, N3-BIS- (2-MERCAPTOETHYL) ISOPHTHALAMIDE (NBMI) treatment for 14 days, administered as four capsules of 100 mg of NBMI every 24 hours.
干预措施: (N1, N3-bis(2- mercaptoethyl)isophthalamide) (Drug)
Arm B: Placebo
(Excipients microcrystalline cellulose, silica and magnesium stearate) capsules will be administered every 24 hours for 14 days.
干预措施: Excipients microcrystalline cellulose, silica and magnesium stearate (Other)
结局指标
主要结局
Measure the "Change in the subject's urine mercury levels"
时间窗: Baseline (Before) treatment, Fourteen (14) days after the start of treatment, Fourteen (14) days after the end of treatment
Evaluation of the difference in mercury levels in the urine as percentage of mercury concentration levels will be determined. The percentage is calculated by comparing baseline mercury concentration levels, against the levels observed at 14-day and 28-days follow-up visits. A rule of three is applied to determine the percentage (%) of change. The analysis of total Hg concentration will be done via Cold Vapor Atomic Absorption spectrometry
次要结局
- Measure the "Change in the subject's blood glucose levels"(Baseline (Before) treatment, Fourteen (14) days after the start of treatment, Fourteen (14) days after the end of treatment)
- Measure the "Frequency and Severity of Adverse Events"(From the first dose of study medication until the Day 56 visit.)
- Measure subject's "Variations in Mental Response ".(Baseline (Before) treatment, Fourteen (14) days after the start of treatment, Fourteen (14) days after the end of treatment)
- Measure subject's "Variations in Weight".(Baseline (Before) treatment, Fourteen (14) days after the start of treatment, Fourteen (14) days after the end of treatment)
- Measure subject's "Variations in Height".(Baseline (Before) treatment, Fourteen (14) days after the start of treatment, Fourteen (14) days after the end of treatment)
- Mercury intoxication measured by Medical Intoxication Score(Baseline (Before) treatment, Fourteen (14) days after the start of treatment, Fourteen (14) days after the end of treatment)
- Measure the "Change in the subject's blood iron levels"(Baseline (Before) treatment, Fourteen (14) days after the start of treatment, Fourteen (14) days after the end of treatment)
- Measure the "Change in the subject's renal function"(Baseline (Before) treatment, Fourteen (14) days after the start of treatment, Fourteen (14) days after the end of treatment)
- Measure subject's "Variations in General Clinical examination".(Baseline (Before) treatment, Fourteen (14) days after the start of treatment, Fourteen (14) days after the end of treatment)