Trial Outcomes & Findings for In-Vivo Assessment of Silver Biomaterial Nano-Toxicity 32 Ppm (NCT NCT01405794)

Results Overview

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

12 participants

Primary outcome timeframe

14 Days

Results posted on

2016-07-04

Participant Flow

Participant milestones

Participant milestones
Measure	All Study Participants All participants were dosed with the placebo (14 days), then they all had a 72hr washout period. Last all participants were dosed with the 32ppm Oral Silver for (14 days).
First Dose Placebo (14 Days) STARTED	12
First Dose Placebo (14 Days) COMPLETED	12
First Dose Placebo (14 Days) NOT COMPLETED	0
72 hr Washout STARTED	12
72 hr Washout COMPLETED	12
72 hr Washout NOT COMPLETED	0
Second Dose 32ppm Oral Silver (14 Days) STARTED	12
Second Dose 32ppm Oral Silver (14 Days) COMPLETED	12
Second Dose 32ppm Oral Silver (14 Days) NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=12 Participants
Age, Continuous	28.8 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change Sodium Blood Levels	141.8 mmol/L Standard Deviation 1.6	141.2 mmol/L Standard Deviation 1.9

PRIMARY outcome

Timeframe: 14 days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change Potassium Blood Levels	4.5 mmol/L Standard Deviation 0.4	4.4 mmol/L Standard Deviation 0.3

PRIMARY outcome

Timeframe: 14 days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change in Chloride Blood Levels	105.0 mmol/L Standard Deviation 2.4	105.5 mmol/L Standard Deviation 2.3

PRIMARY outcome

Timeframe: 14 days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change in Carbon Dioxide Blood Levels	26.5 mmol/L Standard Deviation 2.3	26.8 mmol/L Standard Deviation 2.2

PRIMARY outcome

Timeframe: 14 days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Urea Nitrogen Blood Levels	16.9 mg/dL Standard Deviation 4.0	16.7 mg/dL Standard Deviation 4.1

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Creatinine Blood Levels	0.92 mg/dL Standard Deviation 0.16	0.88 mg/dL Standard Deviation 0.14

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Glucose Blood Levels	85.9 mg/dl Standard Deviation 10.7	83.5 mg/dl Standard Deviation 9.9

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Alkaline Phosphatase Blood Level	89.0 U/L Standard Deviation 60.4	85.4 U/L Standard Deviation 48.5

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Aspartate Aminotransferase Blood Level	29.1 U/L Standard Deviation 7.9	30.9 U/L Standard Deviation 12.4

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Alanine Aminotransferase Blood Level	36.1 U/L Standard Deviation 11.7	34.7 U/L Standard Deviation 11.0

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change in Total Protein Blood Levels	7.1 g/dL Standard Deviation 0.5	7.4 g/dL Standard Deviation 0.5

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Total Bilirubin Blood Levels	0.7 mg/dL Standard Deviation 0.3	0.8 mg/dL Standard Deviation 0.4

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Albumin Blood Levels	4.3 g/dL Standard Deviation 0.4	4.4 g/dL Standard Deviation 0.4

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Calcium Blood Level	9.4 mg/dL Standard Deviation 0.4	9.4 mg/dL Standard Deviation 0.5

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In White Blood Count Blood Levels	5.99 k/uL Standard Deviation 1.24	5.92 k/uL Standard Deviation 1.45

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Red Blood Count Blood Levels	5.07 M/uL Standard Deviation 0.55	5.07 M/uL Standard Deviation 0.45

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Hemoglobin Blood Levels	15.5 gm/dL Standard Deviation 1.4	15.5 gm/dL Standard Deviation 1.2

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Hematocrit Blood Levels	45.0 percent Standard Deviation 3.5	45.4 percent Standard Deviation 3.5

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Mean Corpuscular Volume Blood Levels	89.1 fL Standard Deviation 3.8	89.6 fL Standard Deviation 3.8

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Mean Corpuscular Hemoglobin Concentration Blood Levels	34.5 gm/dL Standard Deviation 1.0	34.2 gm/dL Standard Deviation 0.9

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Platelet Blood Levels	268 k/uL Standard Deviation 59	253 k/uL Standard Deviation 54

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Granulocytes Blood Levels	52.6 percent Standard Deviation 6.9	53.4 percent Standard Deviation 7.6

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Lymphocytes Blood Levels	36.7 percent Standard Deviation 6.4	36.8 percent Standard Deviation 6.9

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Monocytes Blood Levels	6.4 percent Standard Deviation 1.1	6.0 percent Standard Deviation 1.3

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Basophils Blood Levels	0.8 percent Standard Deviation 0.2	0.7 percent Standard Deviation 0.3

PRIMARY outcome

Timeframe: 14 Days

Evaluation of Placebo Group and Silver Particle Group (dose - 32ppm)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Change In Eosinophils Blood Levels	3.4 percent Standard Deviation 1.5	3.1 percent Standard Deviation 1.5

PRIMARY outcome

Timeframe: 14 Days

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.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Cytochrome P450 Assay on Dextromethorphan in Participants	5.53 ng/ml Standard Deviation 5.04	2.18 ng/ml Standard Deviation 1.84

PRIMARY outcome

Timeframe: 14 Days

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.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Cytochrome P450 Assay on Losartan in Participants	1.62 ng/ml Standard Deviation 0.42	1.76 ng/ml Standard Deviation 0.45

PRIMARY outcome

Timeframe: 14 Days

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.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Cytochrome P450 Assay on Caffeine in Participants	3.34 ng/ml Standard Deviation 0.28	3.68 ng/ml Standard Deviation 0.64

PRIMARY outcome

Timeframe: 14 Days

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.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Cytochrome P450 Assay on Omeprazole in Participants	2.19 ng/ml Standard Deviation 1.14	1.81 ng/ml Standard Deviation 0.57

PRIMARY outcome

Timeframe: 14 Days

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.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Cytochrome P450 Assay on Midazolam in Participants	9.62 ng/ml Standard Deviation 0.83	9.18 ng/ml Standard Deviation 1.05

SECONDARY outcome

Timeframe: 14 Days

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.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants	32ppm Oral Silver n=12 Participants
Cytochrome P450 Assay on Chlorozoxazone in Participants Dosed With Silver	2311 ng/ml Standard Deviation 494	1912 ng/ml Standard Deviation 334

SECONDARY outcome

Timeframe: Baseline and 14 Days

Assessment only completed on the 32ppm Oral Silver part of the trail

Outcome measures

Outcome measures
Measure	Placebo	32ppm Oral Silver n=12 Participants
Total Change in Systolic Blood Pressure Silver Participants	—	-1.3 mmhg Interval -3.0 to 5.6

SECONDARY outcome

Timeframe: Baseline and 14 Days

Assessment only completed on the 32ppm Oral Silver part of the trail

Outcome measures

Outcome measures
Measure	Placebo	32ppm Oral Silver n=12 Participants
Total Change in Diastolic Blood Pressure Silver Participants	—	-0.7 mmhg Interval -2.5 to 3.8

SECONDARY outcome

Timeframe: Baseline and 14 Days

Assessment only completed on the 32ppm Oral Silver part of the trail

Outcome measures

Outcome measures
Measure	Placebo	32ppm Oral Silver n=12 Participants
Total Change in Heart Rate in Silver Participants	—	-3.1 beats per minute Interval -6.4 to 0.3

Adverse Events

ASAP 32 Ppm Solution Experimental

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Silver Biotics 32 Ppm Diluent

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ASAP 32 Ppm Solution Experimental n=12 participants at risk	Silver Biotics 32 Ppm Diluent n=12 participants at risk
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/12	8.3% 1/12 • Number of events 1

Other adverse events

Adverse event data not reported

Additional Information

Dr. Mark Munger

University of Utah

Phone: 801-581-6165

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place