Pilot Proof of Concept Study of NBMI Treatment of Mercury Intoxication (NBMI)

A Randomized, Placebo-controlled Study to Explore Safety, Dose and Efficacy of NBMI in a Mercury Intoxicated Population

A randomized, placebo controlled, double blind proof of concept study of NBMI in treatment of mercury intoxication.

Study Overview

• Status: Completed
• Conditions: Mercury Poisoning
• Intervention / Treatment: Drug: Emeramide; Drug: Placebo

Detailed Description

The objectives of this study are to evaluate the efficacy and safety of two doses of NBMI compared to placebo in mercury intoxicated patients.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Ecuador
  • Zaruma, Ecuador
    • Hospital Doctor Humberto Molina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

1. Male or female subjects, age between 18 and 65 years, inclusive.
2. Urine-Hg ≥ 15 μg/L.
3. Mercury intoxication medical score sum (Doering et al. 2014) ≥ 5 or medical score sum ≥ 3 in combination with at least two of the following symptoms; social nervousness/withdrawal, irritability, memory loss, metallic taste, mental- and physical fatigue.
4. Has signed informed consent for participation.
5. Willingness and ability to comply with study procedures, visit schedules, and other instructions regarding the study.

Exclusion criteria

1. History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subjects at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
2. Known or a medical history of renal disorder, significant renal failure, or high risk of renal failure.
3. Any clinically significant abnormalities in clinical chemistry or haematology results at the time of screening as judged by the investigator.
4. Known or suspected neurodegenerative disorder including but not limited to stroke, polio, Parkinson's and Alzheimer's disease.
5. Known or suspected drug or alcohol abuse.
6. Positive pregnancy test in women.
7. Serious bacterial and chronic viral infection such as human immunodeficiency virus (HIV) or hepatitis virus.
8. History of severe allergy/hypersensitivity or on-going allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to NBMI.
9. History of allergy/hypersensitivity to bisulphites (e.g. red/white wine).
10. Participation in any other clinical study that included drug treatment within three months of the first administration of investigational product.
11. Use of other therapies for mercury intoxication including metal chelators within three months.
12. Investigator considers subject unlikely to comply with study procedures, restrictions and requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NBMI (Emeramide) 100mg; NBMI oral capsules 100mg administered once daily. Double dummy used for blinding i.e. 2 x 50mg NBMI + 1 x 200mg placebo capsule equals in total 3 capsules administered daily.	Drug: Emeramide; Mercury chelator NBMI ((N1,N3-bis(2-mercaptoethyl) isophthalamide); Other Names: NBMI; Irminix
Experimental: NBMI (Emeramide) 300mg; NBMI oral capsules 300mg administered once daily. Double dummy used for blinding i.e. 2 x 50mg NBMI + 1 x 200mg NBMI capsule equals in total 3 capsules administered daily.	Drug: Emeramide; Mercury chelator NBMI ((N1,N3-bis(2-mercaptoethyl) isophthalamide); Other Names: NBMI; Irminix
Placebo Comparator: Placebo; Placebo oral capsules administered once daily. Double dummy used for blinding i.e. 2 x 50mg size + 1 x 200mg size placebo capsules equal in total 3 capsules administered daily.	Drug: Placebo; NBMI Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mercury Intoxication Medical Score Sum	Changes from baseline in mercury intoxication medical score sum compared between treatment arms.	45 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Individual components of Mercury Intoxication Medical Score Sum	Changes from baseline in individual components of the mercury intoxication medical score sum compared between treatment arms.	45 days
Fatigue score	Changes from baseline in fatigues score sum compared between treatment arms.	15 days
Neuromotoric functions	Changes from baseline in neuromotoric functions objectively assessed and quantified using computerized systems such as CATSYS compared between treatment arms.	45 days
Blood mercury levels	Changes from baseline in blood mercury level compared between treatment arms.	45 days
Urine mercury levels	Changes from baseline in urine mercury level compared between treatment arms.	45 days
NBMI blood levels	NBMI blood levels 0-24 hours after the first and last dose (day 14 dose)	14 days
NBMI urine levels	NBMI urine levels 0-24 hours after the first and last dose (day 14 dose)	14 days
Adverse events	Adverse event frequency, type and severity compared between treatment arms.	45 days
Safety laboratory assessments	Changes from baseline in clinical chemistry and haematology tests compared between treatment arms.	45 days
Vital signs	Changes from baseline in vital signs compared between treatment arms.	45 days

Collaborators and Investigators

• Sponsor: EmeraMed
• Collaborators: NBMI Science AB
• Investigators: Principal Investigator: Augusto Focil Baquerizo, MD, FOMAT Medical Research

Publications and helpful links

General Publications

• Schutzmeier P, Focil Baquerizo A, Castillo-Tandazo W, Focil N, Bose-O'Reilly S. Efficacy of N,N'bis-(2-mercaptoethyl) isophthalamide on mercury intoxication: a randomized controlled trial. Environ Health. 2018 Feb 14;17(1):15. doi: 10.1186/s12940-018-0358-1.

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: June 24, 2015
• First Submitted That Met QC Criteria: June 26, 2015
• First Posted (Estimate): July 1, 2015

Study Record Updates

• Last Update Posted (Actual): March 8, 2021
• Last Update Submitted That Met QC Criteria: March 4, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Mercury toxicity poisoning
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Heavy Metal Poisoning; Poisoning; Mercury Poisoning; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; N,N'-Bis(2-mercaptoethyl)isophthalamide
• Other Study ID Numbers: CTI002