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Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults

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ClinicalTrials.gov Identifier: NCT01681836
Recruitment Status : Completed
First Posted : September 10, 2012
Results First Posted : September 3, 2018
Last Update Posted : September 3, 2018
Sponsor:
Information provided by (Responsible Party):
Kara Hughan, University of Pittsburgh

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Focus of Study of Healthy Adults
Interventions Drug: 15Nitrogen(15N)-labeled sodium nitrite
Drug: 15Nitrogen(15N)-labeled sodium nitrate
Enrollment 11
Recruitment Details Healthy adult participants were recruited between October 2012 and October 2013.
Pre-assignment Details 11 participants recruited; 11 screened; 0 excluded
Arm/Group Title Oral 15N-labeled Sodium Nitrate, Then Sodium Nitrite Oral 15N-labeled Sodium Nitrite, Then Sodium Nitrate
Hide Arm/Group Description 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 20 mg once in first intervention period and oral 15N-labeled sodium nitrate 1,000 mg once in second intervention period (after washout period)
Period Title: First Intervention
Started 6 5
Completed 6 5
Not Completed 0 0
Period Title: Washout Period of 3-7 Days
Started 6 5
Completed 6 5
Not Completed 0 0
Period Title: Second Intervention
Started 6 5
Completed 6 4
Not Completed 0 1
Reason Not Completed
Withdrawal by Subject             0             1
Arm/Group Title Entire Study Population
Hide Arm/Group Description Includes groups randomized to received oral 15N-labeled sodium nitrate first and sodium nitrite first.
Overall Number of Baseline Participants 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 10 participants
30.4
(21 to 39)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Female
5
  50.0%
Male
5
  50.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
  10.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
9
  90.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Systolic blood pressure  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 10 participants
122  (9.2)
Diastolic blood pressure  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 10 participants
75  (9.3)
Mean arterial pressure  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 10 participants
91  (6.8)
Methemoglobin  
Mean (Standard Deviation)
Unit of measure:  Percentage level of methemoglobin
Number Analyzed 10 participants
1.0  (0.2)
1.Primary Outcome
Title Peak Plasma Nitrate Concentration Over 24 Hour Study Period
Hide Description "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
Time Frame measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral 15N-labeled Sodium Nitrate Oral 15N-labeled Sodium Nitrite
Hide Arm/Group Description:
Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period
Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Overall Number of Participants Analyzed 10 10
Mean (Standard Error)
Unit of Measure: microMolar (microM)
769  (38) 41  (3.7)
2.Primary Outcome
Title Peak Plasma Nitrite Concentration Over 24 Hour Study Period
Hide Description "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
Time Frame measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral 15N-labeled Sodium Nitrate Oral 15N-labeled Sodium Nitrite
Hide Arm/Group Description:
Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period
Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Overall Number of Participants Analyzed 10 10
Mean (Standard Error)
Unit of Measure: microM
0.51  (0.1) 5.5  (0.7)
3.Primary Outcome
Title Peak Red Blood Cell (RBC) Iron-nitrosyl Hemoglobin (NO-Hb) Concentrations Over 24 Hour Study Period
Hide Description "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
Time Frame measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral 15N-labeled Sodium Nitrate Oral 15N-labeled Sodium Nitrite
Hide Arm/Group Description:
Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period
Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Overall Number of Participants Analyzed 10 10
Mean (Standard Error)
Unit of Measure: microMolar
NA [1]   (NA) 1.04  (0.22)
[1]
not detectable
4.Secondary Outcome
Title Peak Percentage Level of Methemoglobin Over 24 Hour Study Period
Hide Description "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
Time Frame measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral 15N-labeled Sodium Nitrate Oral 15N-labeled Sodium Nitrite
Hide Arm/Group Description:
Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period
Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Overall Number of Participants Analyzed 10 10
Mean (Standard Error)
Unit of Measure: percentage level
1.24  (0.08) 1.59  (0.09)
5.Secondary Outcome
Title Peak Change in Mean Arterial Pressure Over 24 Hour Study Period
Hide Description "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
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral 15N-labeled Sodium Nitrate Oral 15N-labeled Sodium Nitrite
Hide Arm/Group Description:
Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period
Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Overall Number of Participants Analyzed 10 10
Mean (Standard Error)
Unit of Measure: mmHg
-2.9  (2.1) -10.4  (3.8)
6.Secondary Outcome
Title Peak Change in Systolic Blood Pressure Over 24 Hour Study Period
Hide Description "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
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral 15N-labeled Sodium Nitrate Oral 15N-labeled Sodium Nitrite
Hide Arm/Group Description:
Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period
Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Overall Number of Participants Analyzed 10 10
Mean (Standard Error)
Unit of Measure: mmHg
-0.8  (2.9) -12.1  (10.5)
7.Secondary Outcome
Title Peak Change in Diastolic Blood Pressure Over 24 Hour Study Period
Hide Description "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
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral 15N-labeled Sodium Nitrate Oral 15N-labeled Sodium Nitrite
Hide Arm/Group Description:
Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period
Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Overall Number of Participants Analyzed 10 10
Mean (Standard Error)
Unit of Measure: mmHg
-6.3  (1.2) -8.1  (6.4)
8.Secondary Outcome
Title Peak 15Nitrogen Nitro-conjugated Linoleic Acid (cLA) Concentrations Over 24 Hour Study Period
Hide Description "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
Time Frame measured at time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
maximal at 24 hours with nitrate treatment, not detectable with nitrite treatment
Arm/Group Title Oral 15N-labeled Sodium Nitrate Oral 15N-labeled Sodium Nitrite
Hide Arm/Group Description:
Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period
Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Overall Number of Participants Analyzed 10 10
Median (Full Range)
Unit of Measure: nanoMolar
0.14
(0 to 25.3)
NA [1] 
(NA to NA)
[1]
not detectable
9.Secondary Outcome
Title Percent Platelet Activation at 6 Hours
Hide Description 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
Time Frame measured at 0 (baseline), 6 and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral 15N-labeled Sodium Nitrate Oral 15N-labeled Sodium Nitrite
Hide Arm/Group Description:
Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period
Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Overall Number of Participants Analyzed 10 10
Mean (Standard Error)
Unit of Measure: % of platelets that are activated
9.0  (1.7) 8.3  (1.9)
10.Secondary Outcome
Title Peak Change in Heart Rate Over 24 Hour Study Period
Hide Description "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
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral 15N-labeled Sodium Nitrate Oral 15N-labeled Sodium Nitrite
Hide Arm/Group Description:
Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period
Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
Overall Number of Participants Analyzed 10 10
Mean (Standard Error)
Unit of Measure: beats per minute
-6  (4.1) 9  (4.4)
Time Frame 3-7 days after single dose of each drug
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Oral 15N-labeled Sodium Nitrate Oral 15N-labeled Sodium Nitrite
Hide Arm/Group Description Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period
All-Cause Mortality
Oral 15N-labeled Sodium Nitrate Oral 15N-labeled Sodium Nitrite
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Oral 15N-labeled Sodium Nitrate Oral 15N-labeled Sodium Nitrite
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      0/11 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Oral 15N-labeled Sodium Nitrate Oral 15N-labeled Sodium Nitrite
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/10 (90.00%)      9/11 (81.82%)    
Gastrointestinal disorders     
Nausea   3/10 (30.00%)  3 2/11 (18.18%)  2
Stomach ache   1/10 (10.00%)  1 0/11 (0.00%)  0
Diarrhea   0/10 (0.00%)  0 1/11 (9.09%)  1
General disorders     
Dizziness   0/10 (0.00%)  0 2/11 (18.18%)  2
Mean arterial pressure decrease >20%   0/10 (0.00%)  0 1/11 (9.09%)  1
Nervous system disorders     
Headache   6/10 (60.00%)  6 7/11 (63.64%)  7
Respiratory, thoracic and mediastinal disorders     
Shortness of breath   0/10 (0.00%)  0 1/11 (9.09%)  1
Nasal congestion   1/10 (10.00%)  1 0/11 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Kara Hughan
Organization: University of Pittsburgh
Phone: 412-692-5170
EMail: kara.hughan@chp.edu
Layout table for additonal information
Responsible Party: Kara Hughan, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01681836     History of Changes
Other Study ID Numbers: PRO11120134
First Submitted: July 3, 2012
First Posted: September 10, 2012
Results First Submitted: February 24, 2016
Results First Posted: September 3, 2018
Last Update Posted: September 3, 2018