Trial Outcomes & Findings for Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults (NCT NCT01681836)

NCT ID: NCT01681836

Last Updated: 2018-09-04

Results Overview

"Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 11 participants
• Primary outcome timeframe: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
• Results posted on: 2018-09-04

Participant Flow

Healthy adult participants were recruited between October 2012 and October 2013.

11 participants recruited; 11 screened; 0 excluded

Participant milestones

Measure	Oral 15N-labeled Sodium Nitrate, Then Sodium Nitrite Oral 15N-labeled sodium nitrate 1,000 mg once in first intervention period and oral 15N-labeled sodium nitrite 20 mg once in second intervention period (after washout period)	Oral 15N-labeled Sodium Nitrite, Then Sodium Nitrate Oral 15N-labeled sodium nitrite 20 mg once in first intervention period and oral 15N-labeled sodium nitrate 1,000 mg once in second intervention period (after washout period)
First Intervention STARTED	6	5
First Intervention COMPLETED	6	5
First Intervention NOT COMPLETED	0	0
Washout Period of 3-7 Days STARTED	6	5
Washout Period of 3-7 Days COMPLETED	6	5
Washout Period of 3-7 Days NOT COMPLETED	0	0
Second Intervention STARTED	6	5
Second Intervention COMPLETED	6	4
Second Intervention NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Oral 15N-labeled Sodium Nitrate, Then Sodium Nitrite Oral 15N-labeled sodium nitrate 1,000 mg once in first intervention period and oral 15N-labeled sodium nitrite 20 mg once in second intervention period (after washout period)	Oral 15N-labeled Sodium Nitrite, Then Sodium Nitrate Oral 15N-labeled sodium nitrite 20 mg once in first intervention period and oral 15N-labeled sodium nitrate 1,000 mg once in second intervention period (after washout period)
Second Intervention Withdrawal by Subject	0	1

Baseline Characteristics

Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults

Baseline characteristics by cohort

Measure	Entire Study Population n=10 Participants Includes groups randomized to received oral 15N-labeled sodium nitrate first and sodium nitrite first.
Age, Continuous	30.4 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Systolic blood pressure	122 mmHg STANDARD_DEVIATION 9.2 • n=5 Participants
Diastolic blood pressure	75 mmHg STANDARD_DEVIATION 9.3 • n=5 Participants
Mean arterial pressure	91 mmHg STANDARD_DEVIATION 6.8 • n=5 Participants
Methemoglobin	1.0 percentage level of methemoglobin STANDARD_DEVIATION 0.2 • n=5 Participants

PRIMARY outcome

Timeframe: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses

"Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period

Outcome measures

Measure	Oral 15N-labeled Sodium Nitrate n=10 Participants Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period	Oral 15N-labeled Sodium Nitrite n=10 Participants Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Peak Plasma Nitrate Concentration Over 24 Hour Study Period	769 microMolar (microM) Standard Error 38	41 microMolar (microM) Standard Error 3.7

PRIMARY outcome

Timeframe: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses

"Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period

Outcome measures

Measure	Oral 15N-labeled Sodium Nitrate n=10 Participants Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period	Oral 15N-labeled Sodium Nitrite n=10 Participants Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Peak Plasma Nitrite Concentration Over 24 Hour Study Period	0.51 microM Standard Error 0.1	5.5 microM Standard Error 0.7

PRIMARY outcome

Timeframe: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses

"Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period

Outcome measures

Measure	Oral 15N-labeled Sodium Nitrate n=10 Participants Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period	Oral 15N-labeled Sodium Nitrite n=10 Participants Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Peak Red Blood Cell (RBC) Iron-nitrosyl Hemoglobin (NO-Hb) Concentrations Over 24 Hour Study Period	NA microMolar Standard Error NA not detectable	1.04 microMolar Standard Error 0.22

SECONDARY outcome

Timeframe: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses

"Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period

Outcome measures

Measure	Oral 15N-labeled Sodium Nitrate n=10 Participants Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period	Oral 15N-labeled Sodium Nitrite n=10 Participants Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Peak Percentage Level of Methemoglobin Over 24 Hour Study Period	1.24 percentage level Standard Error 0.08	1.59 percentage level Standard Error 0.09

SECONDARY outcome

Timeframe: measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 0.75 hours reported

"Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period

Outcome measures

Measure	Oral 15N-labeled Sodium Nitrate n=10 Participants Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period	Oral 15N-labeled Sodium Nitrite n=10 Participants Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Peak Change in Mean Arterial Pressure Over 24 Hour Study Period	-2.9 mmHg Standard Error 2.1	-10.4 mmHg Standard Error 3.8

SECONDARY outcome

Timeframe: measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 1.5 hours reported

"Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period

Outcome measures

Measure	Oral 15N-labeled Sodium Nitrate n=10 Participants Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period	Oral 15N-labeled Sodium Nitrite n=10 Participants Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Peak Change in Systolic Blood Pressure Over 24 Hour Study Period	-0.8 mmHg Standard Error 2.9	-12.1 mmHg Standard Error 10.5

SECONDARY outcome

Timeframe: measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 0.75 hours reported

"Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period

Outcome measures

Measure	Oral 15N-labeled Sodium Nitrate n=10 Participants Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period	Oral 15N-labeled Sodium Nitrite n=10 Participants Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Peak Change in Diastolic Blood Pressure Over 24 Hour Study Period	-6.3 mmHg Standard Error 1.2	-8.1 mmHg Standard Error 6.4

SECONDARY outcome

Timeframe: measured at time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose

Population: maximal at 24 hours with nitrate treatment, not detectable with nitrite treatment

"Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period

Outcome measures

Measure	Oral 15N-labeled Sodium Nitrate n=10 Participants Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period	Oral 15N-labeled Sodium Nitrite n=10 Participants Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Peak 15Nitrogen Nitro-conjugated Linoleic Acid (cLA) Concentrations Over 24 Hour Study Period	0.14 nanoMolar Interval 0.0 to 25.3	NA nanoMolar not detectable

SECONDARY outcome

Timeframe: measured at 0 (baseline), 6 and 24 hours post-dose

at timepoint with greatest change from 0 (trough); "Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period; percentage of platelets that express 2 specific markers identifying activated platelets (CD41 and CD62-P) were quantified using flow cytometry

Outcome measures

Measure	Oral 15N-labeled Sodium Nitrate n=10 Participants Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period	Oral 15N-labeled Sodium Nitrite n=10 Participants Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Percent Platelet Activation at 6 Hours	9.0 % of platelets that are activated Standard Error 1.7	8.3 % of platelets that are activated Standard Error 1.9

SECONDARY outcome

Timeframe: measured at 0 (baseline), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 1.5 hours for nitrate and 24 hours for nitrite

"Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period

Outcome measures

Measure	Oral 15N-labeled Sodium Nitrate n=10 Participants Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period	Oral 15N-labeled Sodium Nitrite n=10 Participants Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Peak Change in Heart Rate Over 24 Hour Study Period	-6 beats per minute Standard Error 4.1	9 beats per minute Standard Error 4.4

Adverse Events

Oral 15N-labeled Sodium Nitrate

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Oral 15N-labeled Sodium Nitrite

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Oral 15N-labeled Sodium Nitrate n=10 participants at risk Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period	Oral 15N-labeled Sodium Nitrite n=11 participants at risk Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Nervous system disorders Headache	60.0% 6/10 • Number of events 6 • 3-7 days after single dose of each drug	63.6% 7/11 • Number of events 7 • 3-7 days after single dose of each drug
Gastrointestinal disorders Nausea	30.0% 3/10 • Number of events 3 • 3-7 days after single dose of each drug	18.2% 2/11 • Number of events 2 • 3-7 days after single dose of each drug
General disorders Dizziness	0.00% 0/10 • 3-7 days after single dose of each drug	18.2% 2/11 • Number of events 2 • 3-7 days after single dose of each drug
Gastrointestinal disorders Stomach ache	10.0% 1/10 • Number of events 1 • 3-7 days after single dose of each drug	0.00% 0/11 • 3-7 days after single dose of each drug
Gastrointestinal disorders Diarrhea	0.00% 0/10 • 3-7 days after single dose of each drug	9.1% 1/11 • Number of events 1 • 3-7 days after single dose of each drug
Respiratory, thoracic and mediastinal disorders Shortness of breath	0.00% 0/10 • 3-7 days after single dose of each drug	9.1% 1/11 • Number of events 1 • 3-7 days after single dose of each drug
Respiratory, thoracic and mediastinal disorders Nasal congestion	10.0% 1/10 • Number of events 1 • 3-7 days after single dose of each drug	0.00% 0/11 • 3-7 days after single dose of each drug
General disorders Mean arterial pressure decrease >20%	0.00% 0/10 • 3-7 days after single dose of each drug	9.1% 1/11 • Number of events 1 • 3-7 days after single dose of each drug

Additional Information

Dr. Kara Hughan

University of Pittsburgh

Phone: 412-692-5170

Email: kara.hughan@chp.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place