Trial Outcomes & Findings for In Vivo Assessment of Silver Biomaterial Nano-Toxicity (NCT NCT01243320)

Results Overview

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

36 participants

Primary outcome timeframe

14 Days

Results posted on

2015-08-25

Participant Flow

Participant milestones

Participant milestones
Measure	All Study Participants Study had two dosing phases. All study participants were assigned the 10ppm Oral Silver and proceed to the 32 pm Oral Silver.
10ppm Oral Silver (3 Days) STARTED	36
10ppm Oral Silver (3 Days) COMPLETED	36
10ppm Oral Silver (3 Days) NOT COMPLETED	0
10ppm Oral Silver (7 Days) STARTED	36
10ppm Oral Silver (7 Days) COMPLETED	36
10ppm Oral Silver (7 Days) NOT COMPLETED	0
10ppm Oral Silver (14 Days) STARTED	36
10ppm Oral Silver (14 Days) COMPLETED	36
10ppm Oral Silver (14 Days) NOT COMPLETED	0
Washout (3 Days) STARTED	36
Washout (3 Days) COMPLETED	36
Washout (3 Days) NOT COMPLETED	0
32ppm Oral Silver (14 Days) STARTED	24
32ppm Oral Silver (14 Days) COMPLETED	24
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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Participants n=36 Participants 10 ppm Silver, then 32 ppm Silver
Age, Continuous	47 years STANDARD_DEVIATION 14 • n=93 Participants
Sex: Female, Male Female	17 Participants n=93 Participants
Sex: Female, Male Male	19 Participants n=93 Participants

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change in Sodium Blood Levels	-0.1 mmol/L Interval -0.7 to 0.6	0.2 mmol/L Interval -0.7 to 1.0

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change in Potassium Blood Levels	-0.1 mmol/L Interval -0.3 to 0.02	-0.03 mmol/L Interval -0.2 to 0.1

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change in Chloride Blood Levels	-0.4 mmol/L Interval -1.2 to 0.3	0.04 mmol/L Interval -1.1 to 1.2

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change in Carbon Dioxide Blood Levels	0.5 mmol/L Interval -0.5 to 1.6	-0.04 mmol/L Interval -1.1 to 1.0

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change in Urea Nitrogen Blood Levels	-0.9 mg/dL Interval -1.7 to -0.1	0.5 mg/dL Interval -0.08 to 1.8

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In CreatinineBlood Levels	0.01 mg/dL Interval -0.02 to 0.03	-0.02 mg/dL Interval -0.04 to 0.01

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Glucose Blood Levels	3.6 mg/dL Interval -1.6 to 8.7	-0.7 mg/dL Interval -4.2 to 2.9

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Alkaline Phosphatase Blood Level	-1.4 u/L Interval -3.9 to 1.1	2.0 u/L Interval -1.0 to 5.0

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Aspartate Aminotransferase Blood Level	-0.44 u/L Interval -2.1 to 1.2	2.0 u/L Interval -2.6 to 6.5

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Alanine Aminotransferase Blood Level	-2.6 u/L Interval -4.8 to -0.3	2.3 u/L Interval -1.6 to 6.3

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Total Protein Blood Levels	-0.02 g/dL Interval -0.3 to 0.2	0.2 g/dL Interval -0.001 to 0.4

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Total Bilirubin Blood Levels	-0.02 mg/dL Interval -0.08 to 0.3	-0.03 mg/dL Interval -0.11 to 0.05

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change in Albumin Blood Levels	-0.07 g/dL Interval -0.1 to 0.0004	0.11 g/dL Interval -0.01 to 0.23

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Calcium Blood Level	-0.1 mg/dL Interval -0.2 to 0.04	0.1 mg/dL Interval -0.003 to 0.2

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In White Blood Count Blood Levels	-0.17 k/uL Interval -0.53 to 0.19	-0.09 k/uL Interval -0.68 to 0.49

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Red Blood Count Blood Levels	-0.08 m/uL Interval -0.17 to -0.0001	0.06 m/uL Interval -0.03 to 0.14

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Hemoglobin Blood Levels	-0.2 gm/dL Interval -0.4 to 0.03	0.1 gm/dL Interval -0.2 to 0.4

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Hematocrit Blood Levels	-0.7 percent Interval -1.5 to 0.07	0.8 percent Interval -0.1 to 1.7

PRIMARY outcome

Timeframe: 14 days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Mean Corpuscular Volume Blood Levels	0.1 fL Interval -0.6 to 0.8	0.5 fL Interval -0.1 to 1.2

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Mean Corpuscular Hemoglobin Blood Levels	0.1 pg Interval -0.1 to 0.3	-0.01 pg Interval -0.4 to 0.2

PRIMARY outcome

Timeframe: 14 days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Mean Corpuscular Hemoglobin Concentration Blood Levels	0.1 gm/dL Interval -0.3 to 0.4	-0.3 gm/dL Interval -0.7 to 0.1

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Platelet Blood Levels	5 k/uL Interval -6.0 to 15.0	-4 k/uL Interval -16.0 to 8.0

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Granulocytes Blood Levels	-0.9 percent Interval -3.0 to 1.1	-0.7 percent Interval -4.0 to 2.7

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Lymphocytes Blood Levels	0.7 percent Interval -1.2 to 2.6	1.3 percent Interval -1.5 to 4.1

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change In Monocytes Blood Levels	-0.1 percent Interval -0.6 to 0.4	-0.3 percent Interval -0.8 to 0.3

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change in Basophils Blood Levels	0.04 percent Interval -0.1 to 0.2	0.001 percent Interval -0.1 to 0.1

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change in Eosinophil Blood Levels	-0.06 percent Interval -0.3 to 0.2	-0.2 percent Interval -0.7 to 0.2

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Sputum Reactive Oxygen Species Change	0.89 uM Interval -0.6 to 2.38	-0.44 uM Interval -1.23 to 0.35

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change to Interleukin-8 Receptor	2.19 ng/mL Interval -1.53 to 5.9	6.39 ng/mL Interval -5.83 to 18.6

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change to Interleukin-1 Alpha Receptor	-0.0005 ng/mL Interval -0.0007 to 0.0006	0.0197 ng/mL Interval -0.0014 to 0.0408

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change to Interleukin-1 Beta Receptor	0.017 ng/mL Interval -0.011 to 0.044	0.027 ng/mL Interval -0.058 to 0.112

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change in Monocyte Chemotactic Protein 1	-0.028 ng/mL Interval -0.084 to 0.028	-0.004 ng/mL Interval -0.026 to 0.017

PRIMARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change in Quinone Oxidoreductase 1 Gene	-0.0043 ng/mL Interval -0.0115 to 0.029	-0.0279 ng/mL Interval -0.4671 to 0.4114

SECONDARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Change Systolic Blood Pressure	1.3 mmhg Interval -1.7 to 4.3	-1.3 mmhg Interval -3.0 to 5.6

SECONDARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Mean Change in Diastolic Blood Pressure	-2.4 mmhg Interval -5.5 to 0.7	-0.7 mmhg Interval -2.5 to 3.8

SECONDARY outcome

Timeframe: 14 Days

All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.

Outcome measures

Outcome measures
Measure	10ppm Oral Silver n=36 Participants ASAP Solution 10 ppm: Silver nanoparticles at 10ppm	32ppm Oral Silver n=24 Participants ASAP Solution 32 ppm Diluent: Silver nanoparticles at 32ppm
Mean Change in Heart Rate	-1.9 bpm Interval -5.0 to 1.3	-3.1 bpm Interval -6.4 to 0.3

Adverse Events

10ppm Oral Solution

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

32ppm Oral Solution

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	10ppm Oral Solution n=36 participants at risk All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.	32ppm Oral Solution n=24 participants at risk All participants received the 10ppm Silver, then progressed to the 32 ppm Silver.
Vascular disorders Pulmonary Embolism	2.8% 1/36 • Number of events 1	0.00% 0/24

Other adverse events

Adverse event data not reported

Additional Information

Mark A. Munger, Pharm.D.

University of Utah

Phone: 8015816165

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place