Trial Outcomes & Findings for Oral Nitrite in Adults With Metabolic Syndrome and Hypertension (NCT NCT01681810)

Last Updated: 2019-04-16

Results Overview

Change in insulin stimulated glucose disposal was assessed during the 4-hour hyperinsulinemic euglycemic clamp at end of the 12 weeks and was compared to baseline (pre-nitrite). Insulin stimulated glucose disposal (mg/min) was calculated in the final 20 minutes of the 4-hour clamp at steady state and expressed as mg per kg lean body mass (as measured by DEXA) per minute. HumuLIN R regular insulin was infused at a rate of 40 microUnits/m2/min. A non-radioactive glucose isotope dilution (Isotec, Inc) was delivered as a primed, then constant infusion of the 98+% enriched stable isotope of D-glucose \[6,6-D2\] (0.22 umol x kg-1, 17.6 umol x kg-1 prime). Plasma glucose was clamped between 85-95 mg/dL with a variable infusion of 20% dextrose in water. The rate of dextrose infusion was adjusted based on arterialized plasma glucose measurements obtained every 5 minutes.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

measured at 0 (baseline) and at 12 weeks

Results posted on

2019-04-16

Participant Flow

Subjects 18-60 years with metabolic syndrome and hypertension were recruited through the University of Pittsburgh Research Participant Registry, University of Pittsburgh Nutrition and Obesity Research Center Registry, university and University of Pittsburgh Medical Center hospital electronic and paper advertising, and radio and bus advertising.

Twenty four age eligible subjects were consented and eligibility was confirmed. Four were excluded after eligibility confirmed due to poor IV access or not showing to baseline assessment visits, all prior to starting nitrite drug.

Participant milestones

Participant milestones
Measure	14Nitrogen Sodium Nitrite sodium nitrite 40 mg three times a day for 12 weeks 14Nitrogen Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times a day for 12 weeks
Overall Study STARTED	20
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

displaying sex-specific waist circumference as per eligibility criteria

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	14Nitrogen Sodium Nitrite n=20 Participants sodium nitrite 40 mg three times a day for 12 weeks 14Nitrogen Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times a day for 12 weeks
Age, Continuous	52.4 years n=20 Participants
Sex: Female, Male Female	15 Participants n=20 Participants
Sex: Female, Male Male	5 Participants n=20 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=20 Participants
Race (NIH/OMB) Asian	0 Participants n=20 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=20 Participants
Race (NIH/OMB) Black or African American	6 Participants n=20 Participants
Race (NIH/OMB) White	12 Participants n=20 Participants
Race (NIH/OMB) More than one race	0 Participants n=20 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=20 Participants
Region of Enrollment United States	20 participants n=20 Participants
Systolic blood pressure (SBP)	146 mmHg STANDARD_DEVIATION 15.7 • n=20 Participants
Diastolic blood pressure (DBP)	87.8 mmHg STANDARD_DEVIATION 8.57 • n=20 Participants
Mean arterial pressure (MAP)	109 mmHg STANDARD_DEVIATION 11.1 • n=20 Participants
Body mass index (BMI)	40.8 kg/m^2 STANDARD_DEVIATION 6.63 • n=20 Participants
Waist circumference-male	133.3 cm STANDARD_DEVIATION 11.82 • n=5 Participants • displaying sex-specific waist circumference as per eligibility criteria
Waist circumference-female	116.8 cm STANDARD_DEVIATION 13.07 • n=15 Participants • displaying sex-specific waist circumference as per eligibility criteria
Thyroid stimulating hormone (TSH)	1.93 mIU/mL STANDARD_DEVIATION 1.45 • n=20 Participants
Hemoglobin	14.1 g/dL STANDARD_DEVIATION 1.25 • n=20 Participants

PRIMARY outcome

Timeframe: measured at 0 (baseline) and at 12 weeks

Population: The pre-drug hyperinsulinemic euglycemic clamp isotope data for 1 subject (used to determine insulin stimulated glucose disposal) was not interpretable despite repeat of the mass spectrometry assay. Therefore, the pre- and post- outcome measure for this subject was removed from analysis, giving a n=19 sample size for this analysis.

Outcome measures

Outcome measures
Measure	14Nitrogen Sodium Nitrite n=19 Participants sodium nitrite 40 mg three times a day for 12 weeks 14Nitrogen Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times a day for 12 weeks
Change in Insulin Stimulated Glucose Disposal Over 12 Week Study Period	0.76 mg/kg lean body mass/minute Standard Error 0.58

SECONDARY outcome

Timeframe: measured at 0 (baseline) and bi-weekly over 12 weeks

Peak change in systolic blood pressure (SBP) on sodium nitrite compared to baseline. Subjects performed bi-weekly blinded automated blood pressures with a Dinamap DPC200X (GE Medical Systems Information Technology) in triplicate at study visits beginning 30 minutes after directly observed nitrite dosing. Five minute intervals were maintained between measurements while in the supine position with legs uncrossed and sitting upright in a hospital bed in a quiet room. The final 2 of 3 SBP measurements were averaged.

Outcome measures

Outcome measures
Measure	14Nitrogen Sodium Nitrite n=20 Participants sodium nitrite 40 mg three times a day for 12 weeks 14Nitrogen Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times a day for 12 weeks
Peak Change in Systolic Blood Pressure Over 12 Week Study Period	-10.45 mmHg Standard Error 3.01

SECONDARY outcome

Timeframe: measured at 0 (baseline) and bi-weekly over 12 weeks

Peak change in diastolic blood pressure (DBP) on sodium nitrite compared to baseline. Subjects performed bi-weekly blinded automated blood pressures with a Dinamap DPC200X (GE Medical Systems Information Technology) in triplicate at study visits beginning 30 minutes after directly observed nitrite dosing. Five minute intervals were maintained between measurements while in the supine position with legs uncrossed and sitting upright in a hospital bed in a quiet room. The final 2 of 3 DBP measurements were averaged.

Outcome measures

Outcome measures
Measure	14Nitrogen Sodium Nitrite n=20 Participants sodium nitrite 40 mg three times a day for 12 weeks 14Nitrogen Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times a day for 12 weeks
Peak Change in Diastolic Blood Pressure Over 12 Week Study Period	-13.05 mmHg Standard Error 2.2

SECONDARY outcome

Timeframe: measured at 0 (baseline) and bi-weekly over 12 weeks

Peak change in mean arterial pressure (MAP) on sodium nitrite compared to baseline. Subjects performed bi-weekly blinded automated blood pressures with a Dinamap DPC200X (GE Medical Systems Information Technology) in triplicate at study visits beginning 30 minutes after directly observed nitrite dosing. Five minute intervals were maintained between measurements while in the supine position with legs uncrossed and sitting upright in a hospital bed in a quiet room. The final 2 of 3 MAP measurements were averaged.

Outcome measures

Outcome measures
Measure	14Nitrogen Sodium Nitrite n=20 Participants sodium nitrite 40 mg three times a day for 12 weeks 14Nitrogen Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times a day for 12 weeks
Peak Change in Mean Arterial Pressure Over 12 Week Study Period	-12.00 mmHg Standard Error 2.15

SECONDARY outcome

Timeframe: measured at 0 (baseline) and bi-weekly over 12 weeks

Peak change in methemoglobin on sodium nitrite compared to baseline. Methemoglobin was assessed bi-weekly at study visits 30 minutes after directly observed nitrite dosing using noninvasive co-oximetry (Masimo Corp, Irvine, CA).

Outcome measures

Outcome measures
Measure	14Nitrogen Sodium Nitrite n=20 Participants sodium nitrite 40 mg three times a day for 12 weeks 14Nitrogen Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times a day for 12 weeks
Peak Change in Methemoglobin Over 12 Week Study Period	0.42 percentage of total hemoglobin Standard Error 0.11

Adverse Events

14Nitrogen Sodium Nitrite

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	14Nitrogen Sodium Nitrite n=20 participants at risk sodium nitrite 40 mg three times a day for 12 weeks 14Nitrogen Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times a day for 12 weeks
Gastrointestinal disorders Abdominal pain	20.0% 4/20 • Number of events 6 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Gastrointestinal disorders Nausea	45.0% 9/20 • Number of events 9 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Gastrointestinal disorders Vomiting	20.0% 4/20 • Number of events 4 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Gastrointestinal disorders Diarrhea	10.0% 2/20 • Number of events 2 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Nervous system disorders Headache	75.0% 15/20 • Number of events 62 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Nervous system disorders Dizziness	25.0% 5/20 • Number of events 14 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Respiratory, thoracic and mediastinal disorders Shortness of breath	10.0% 2/20 • Number of events 10 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Respiratory, thoracic and mediastinal disorders Tachypnea	10.0% 2/20 • Number of events 6 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Vascular disorders Flushing	25.0% 5/20 • Number of events 5 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Cardiac disorders Tachycardia	10.0% 2/20 • Number of events 5 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
General disorders Fatigue	10.0% 2/20 • Number of events 3 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Respiratory, thoracic and mediastinal disorders Upper respiratory symptoms	45.0% 9/20 • Number of events 15 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Skin and subcutaneous tissue disorders Dry mouth	30.0% 6/20 • Number of events 15 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Skin and subcutaneous tissue disorders Sore mouth	10.0% 2/20 • Number of events 2 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Musculoskeletal and connective tissue disorders Back pain	25.0% 5/20 • Number of events 21 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Musculoskeletal and connective tissue disorders Joint pain	20.0% 4/20 • Number of events 7 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Musculoskeletal and connective tissue disorders Arm/hand pain (non-joint)	10.0% 2/20 • Number of events 2 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Musculoskeletal and connective tissue disorders Myalgias	10.0% 2/20 • Number of events 2 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
Psychiatric disorders Anxiety	10.0% 2/20 • Number of events 5 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.
General disorders Sleep disruption	10.0% 2/20 • Number of events 9 • Adverse event (AE) collection occurred throughout 12 weeks of study drug treatment until 1 month after completing study drug. Adverse event (AE) collection occurred after eligibility was confirmed. AE collection was then queried bi-weekly by standard questionnaire, daily by standard diary card logged by participants, and with regular investigator assessment. First AE assessment began at first baseline assessment study visit prior to first dose of study drug visit.

Additional Information

Dr. Kara Hughan

University of Pittsburgh

Phone: 4126925173

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place