Efficacy of N,N'bis-(2-mercaptoethyl) isophthalamide on mercury intoxication: a randomized controlled trial

Abstract

Background: Chronic mercury intoxication is a severe health issue and occurs especially in gold mining communities. Common chelators used for improving mercury elimination are not everywhere available and challenged by poor cell wall penetration. This study is part of a feasibility trial and the aim was to gather first information about the efficacy of the newly developed chelator N,N'bis-(2-mercaptoethyl) isophthalamide (NBMI) on chronic mercury intoxication.

Methods: In this three-armed, placebo-controlled randomized trial, 36 miners with mercury urine levels exceeding 15 μg/l were administered 100 mg NBMI, 300 mg NBMI or placebo for 14 days. Levels of mercury in urine [μg/l and μg/g creatinine] and plasma l were analyzed. Therapeutic effect was assessed using the medical intoxication score (MIS) and its single health outcomes (e.g. excessive salivation, sleeping problems), fatigue scores, a neuromotoric test battery (CATSYS) and a neurological outcome (Finger to nose test).

Results: Physical fatigue was significantly decreased in the 300 mg NBMI group compared to the control. Mercury concentration in urine following 300 mg NBMI treatment was significantly lowered compared to control, however, this effect was less distinct with adjustment for creatinine.

Conclusion: NBMI showed an effect on physical fatigue and there were indications to positive effects on other symptoms as well. More comprehensive studies are mandatory to verify the effects of NBMI as a novel tool for treating mercury intoxications.

Trial registration: ClinicalTrials.gov Identifier: NCT02486289 . Date of registration: June 24, 2015.

Keywords: Chelation therapy; Chronic mercury intoxication; Gold mining; Mercury; NBMI.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol and study informed consent forms (ICF) were submitted to the Institutional Review Board (IRB) of the Universidad de San Francisco de Quito, Diego de Robles y Vía Interoceánica, Quito, Ecuador for review. After requested revisions the study protocol and ICF were approved in writing on 26 May 2015. The Regulatory Authorities required revisions and protocol (amendment 2) and ICF were therefore re-submitted to the IRB and approved on 27 Jul 2015.

The study protocol was amended once during the study (amendment 3, see Additional file 1) to protocol. The amendment, including ICF was submitted to the IRB and approved on 30 September 2015.

The study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Conference on Harmonisation/Good Clinical Practice and applicable regulatory requirements on Bioethics.

Consent for publication

Not applicable.

Competing interests

EmeraMed Ltd. reimbursed the author’s (Paul Schutzmeier) expenses connected with the project and the publication. The authors declare that they have no competing interests.

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Figures

Fig. 1

Chemical structure and basic facts

Fig. 2

Subject Disposition

Fig. 3

Overview of mean fatigue scores and change over follow up. The bars show the physical and mental fatigue scores at baseline, Day 15 and Day 45 stratified by treatment arm. The data is expressed as mean ± SD, the asterisk indicate statistical difference to the placebo group at p < 0.05

Fig. 4

Changes in urine values after follow-up. The creatinine adjusted, and unadjusted urine values are shown stratified by treatment group and examination day. Green bars signify median urine values, yellow bars median changes from baseline values