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

The investigators propose to study oral commercial silver nanoparticle products on human enzyme activity.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: 32ppm Silver Particle; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112-5820
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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 Chronic Obstructive Pulmonary Disease;
• 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.

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 32ppm Oral Silver; 14 Days Active Silver Solution	Drug: 32ppm Silver Particle; Oral silver dose of 32ppm
Placebo Comparator: Sterile Water; No Silver Nanoparticles	Drug: Placebo; Sterile Water No Silver

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change Sodium Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change Potassium Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 days
Change in Chloride Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 days
Change in Carbon Dioxide Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 days
Change In Urea Nitrogen Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 days
Change In Creatinine Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Glucose Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Alkaline Phosphatase Blood Level	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Aspartate Aminotransferase Blood Level	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Alanine Aminotransferase Blood Level	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change in Total Protein Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Total Bilirubin Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Albumin Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Calcium Blood Level	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In White Blood Count Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Red Blood Count Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Hemoglobin Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Hematocrit Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Mean Corpuscular Volume Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Mean Corpuscular Hemoglobin Concentration Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Platelet Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Granulocytes Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Lymphocytes Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Monocytes Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Basophils Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Change In Eosinophils Blood Levels	Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)	14 Days
Cytochrome P450 Assay on Dextromethorphan in Participants	Assessment Placebo (14 Days) and 32ppm Oral Silver (14 Days). Cytochrome P450 assay is used to determine the function of how Dextromethorphan metabolized. The value represents the peak absorption of the 450 enzyme when dextromethorphan is given during the Silver or Placebo Arm.	14 Days
Cytochrome P450 Assay on Losartan in Participants	Assessment Placebo (14 Days) and 32ppm Oral Silver (14 Days). Cytochrome P450 assay is used to determine the function of how Dextromethorphan metabolized. The value represents the peak absorption of the 450 enzyme when dextromethorphan is given during the Silver or Placebo Arm.	14 Days
Cytochrome P450 Assay on Caffeine in Participants	Assessment Placebo (14 Days) and 32ppm Oral Silver (14 Days). Cytochrome P450 assay is used to determine the function of how Dextromethorphan metabolized. The value represents the peak absorption of the 450 enzyme when dextromethorphan is given during the Silver or Placebo Arm.	14 Days
Cytochrome P450 Assay on Omeprazole in Participants	Assessment Placebo (14 Days) and 32ppm Oral Silver (14 Days). Cytochrome P450 assay is used to determine the function of how Dextromethorphan metabolized. The value represents the peak absorption of the 450 enzyme when dextromethorphan is given during the Silver or Placebo Arm.	14 Days
Cytochrome P450 Assay on Midazolam in Participants	Assessment Placebo (14 Days) and 32ppm Oral Silver (14 Days). Cytochrome P450 assay is used to determine the function of how Dextromethorphan metabolized. The value represents the peak absorption of the 450 enzyme when dextromethorphan is given during the Silver or Placebo Arm.	14 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytochrome P450 Assay on Chlorozoxazone in Participants Dosed With Silver	Assessment Placebo (14 Days) and 32ppm Oral Silver (14 Days). Cytochrome P450 assay is used to determine the function of how Dextromethorphan metabolized. The value represents the peak absorption of the 450 enzyme when dextromethorphan is given during the Silver or Placebo Arm.	14 Days
Total Change in Systolic Blood Pressure Silver Participants	Assessment only completed on the 32ppm Oral Silver part of the trail	Baseline and 14 Days
Total Change in Diastolic Blood Pressure Silver Participants	Assessment only completed on the 32ppm Oral Silver part of the trail	Baseline and 14 Days
Total Change in Heart Rate in Silver Participants	Assessment only completed on the 32ppm Oral Silver part of the trail	Baseline and 14 Days

Collaborators and Investigators

• Sponsor: University of Utah
• Investigators: Principal Investigator: Mark Munger, Pharm.D., University of Utah

Publications and helpful links

General Publications

• Munger MA, Radwanski P, Hadlock GC, Stoddard G, Shaaban A, Falconer J, Grainger DW, Deering-Rice CE. In vivo human time-exposure study of orally dosed commercial silver nanoparticles. Nanomedicine. 2014 Jan;10(1):1-9. doi: 10.1016/j.nano.2013.06.010. Epub 2013 Jun 28.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: July 19, 2011
• First Submitted That Met QC Criteria: July 28, 2011
• First Posted (Estimate): July 29, 2011

Study Record Updates

• Last Update Posted (Estimate): July 4, 2016
• Last Update Submitted That Met QC Criteria: May 25, 2016
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Other Study ID Numbers: 50310 (MSD Sharp&Dohme GmbH)