In-Vivo Assessment of Silver Biomaterial Nano-Toxicity 32 Ppm

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
mark munger, University of Utah
ClinicalTrials.gov Identifier:
NCT01405794
First received: July 19, 2011
Last updated: November 15, 2011
Last verified: November 2011
  Purpose

Nanotechnology is the controlled generation and manipulation of matter in dimensions less than 100 nm. Silver has been used for its bactericidal properties. The investigators propose to study the American Biotech Laboratory 32 ppm silver solution over a 14-day period in human volunteers to determine the toxicity and to quantify cytochrome P450 enzyme effects of this solution. This is a prospective, placebo-controlled, single-blind, randomized, cross-over study of 24 healthy subjects. Twelve subjects will be admitted to the CCTS for 3 (Day -1, 0, and 14) overnight stays to determine the solution effects on cytochrome P450 enzyme inhibition or induction.


Condition Intervention Phase
Healthy
Drug: ASAP Solution 32 ppm
Drug: Silver Biotics 32ppm Solution Diluent
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: In-Vivo Assessment of Silver Biomaterial Nano-Toxicity 32 Ppm

Further study details as provided by University of Utah:

Primary Outcome Measures:
  • Quantify differences between variables on a Comprehensive Metabolic Panel, Urinalysis, and CBC with Platelet Count from exposure to 32ppm Silver Solution versus the placebo diluent (water). [ Time Frame: 14 Days ] [ Designated as safety issue: Yes ]
    Routine standardized blood and urine analyses will be collected at baseline and compared to end of the 14-day exposure for both teh active comparator versus the placebo comparator.


Secondary Outcome Measures:
  • Quantify Silver in Serum and Urine by Measurement of Silver Metallic Ions (Ag0) [ Time Frame: 14 Days ] [ Designated as safety issue: Yes ]
    The amount of Ag0 ingested will be measured in the serum and urine of each subject.

  • Quantify select cytochrome P450 activity effects of 32 ppm Silver Nanoparticle Solution [ Time Frame: 14-Day ] [ Designated as safety issue: Yes ]
    Standardized drug probes for human cytochrome P450 enzymes (1A2, 2C9, 2D6, 3A4, and 2E1) will be administered on Day 0 (baseline), Day 1 (single-dose), and Day 14 (multiple dose).

  • Measure Presence of Reactive Oxygen Species and Determine the Presence of Pro-Inflammatory Genetic Markers from Induced Sputum [ Time Frame: 14 Days ] [ Designated as safety issue: Yes ]
    Induced sputum will be collected and analyzed for white blood cell counts, presence of reactive oxygen species and pro-inflammtory cytokines.

  • Qualify Silver Nanoparticle 32 ppm Retention in Human Organ Systems [ Time Frame: 14 Day ] [ Designated as safety issue: Yes ]
    All eligible subjects will undergo a cardiac, lung, and abdominal MRI to identify macroscopic or structural abnormalities


Estimated Enrollment: 24
Study Start Date: July 2011
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ASAP 32 ppm Solution Experimental
ASAP Solution 32 ppm, Silver Biotics 32 ppm Solution
Drug: ASAP Solution 32 ppm
32 ppm Silver Nanosolution
Placebo Comparator: Silver Biotics 32 ppm Diluent
Silver Biotics 32 ppm Diluent
Drug: Silver Biotics 32ppm Solution Diluent
32 ppm Silver Nanosolution Diluent.

Detailed Description:

Nanotechnology is a rapidly evolving industry with an expected impact to surpass the Industrial Revolution Nanotechnology.1-2 The estimated worldwide market for products produced using nanotechnology is estimated to reach US$1 trillion by 2015.3 Nanotechnology is the controlled generation and manipulation of matter in dimensions less than 100 nm.4 Design of these nano-particles results in novel physiochemical characteristics when compared to identical bulk material, including increased surface reactivity, solubility, shape and aggregation.1 The exponential increase in the ratio of surface-to-total atoms with decreasing particle size also results in greater bioactivity per unit mass.5-7

Silver has been used for numerous medicinal purposes, including bactericidal properties, for generations. Silver coins were added regularly to drinking water barrels to protect from bacterial contamination.10 As a result of the discovery of penicillin in the 1940s, the emergence of biochemical antibiotics caused silver use to decline. More recently, as a result of the emergence of resistant strains of bacteria and viruses, silver has re-emerged as an antimicrobial agent for study.

American Biotech Laboratory (Alpine, Utah), has developed a 32 ppm nanoparticle silver solution for the study and treatment of a variety of infectious diseases. In vitro testing of the solution against both gram positive and gram negative organisms demonstrated MIC values ranged between 1.25 ppm and 2.5 ppm with the exception of E faecalis and S aureus which had MICs of 10 ppm and 5 ppm, respectively.8 A detailed description of the manufacturing process is available online at www.uspto.gov under patent number 6,214,299. The solution is currently marketed worldwide as ASAP Solution and has current sales of more than 1,500,000 bottles.

The investigators have been conducting a safety study on American Biotech Laboratories 10 ppm nanoparticle solution for the past 4 months. To date, no metabolic or hemodynamic adverse events have been identified. Radiologic imaging of the subjects ingesting the 10ppm solution has not demonstrated any identification of silver particles in the heart, lungs, liver, kidney or spleen. Sputum pathology studies have not demonstrated any appearance of pro-inflammatory cytokines or reactive oxygen species. The next logical step is to study the higher dose of 32 ppm using the similar methodology in the 10ppm study.

Nanosilver particles may also have effects on the drug metabolism through the human microsomal cytochrome P450 system. To test this hypothesis in-vitro, the investigators studied the effect of the 32 ppm nanoparticle solution using Caco-2 and HepG2 cells. The study showed that several of cytochrome P450 system enzymes have effects on cell function as it relates to the metabolism and elimination of drugs and other xenobiotics.9

The investigators propose to study the American Biotech Laboratory 32 ppm silver solution through a single 14 time-length exposures in human volunteers to determine the toxicity, if any, of this solution.

Hypothesis: A 14-day exposure of the American Biotech Laboratory 32 ppm silver solution will not evidence in clinically significant metabolic, hemodynamic, imaging or select cytochrome P450 activities in healthy human volunteers.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 24 subjects 18-80 years old without debilitating chronic disease or history of cardiovascular event.

Exclusion Criteria:

  • Women physically capable of becoming pregnant, who are not using 2 barrier methods of birth control;
  • Any female who is nursing;
  • History of heavy metal allergy;
  • History of asthma or COPD;
  • History of renal impairment;
  • Symptoms of active upper respiratory disease at time of consent;
  • Smoking more than 5 cigarettes or equivalent and not able to stop for 48 hours;
  • Ability to discontinue chronic medications or nutraceuticals for 20 days or 5 half-lives of the agent, whichever is longer.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01405794

Locations
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112-5820
Sponsors and Collaborators
University of Utah
Investigators
Principal Investigator: Mark Munger, Pharm.D. University of Utah
  More Information

No publications provided by University of Utah

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: mark munger, Professor, University of Utah
ClinicalTrials.gov Identifier: NCT01405794     History of Changes
Other Study ID Numbers: 50310
Study First Received: July 19, 2011
Last Updated: November 15, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014