Trial Outcomes & Findings for Study of Nicotinamide in Early Onset Preeclampsia (NCT NCT03419364)

NCT ID: NCT03419364

Last Updated: 2022-09-08

Results Overview

Blood pressure (mmHg) will be used to observe the effect of nicotinamide. The highest MAP (defined as the highest MAP within the 24 hour period prior to the administration of study agent) and the highest MAP through 24 hours after study drug administration.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 23 participants
• Primary outcome timeframe: Baseline, 48 hours
• Results posted on: 2022-09-08

Participant Flow

Participant milestones

Measure	Nicotinamide - Pre-eclampsia All participants will receive study agent nicotinamide: 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday	Nicotinamide - Healthy Pregnant All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning	Nicotinamide - Healthy Non-Pregnant All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning
Overall Study STARTED	11	6	6
Overall Study Signed Consent	11	6	6
Overall Study Received Intervention	9	6	6
Overall Study COMPLETED	9	6	6
Overall Study NOT COMPLETED	2	0	0

Reasons for withdrawal

Measure	Nicotinamide - Pre-eclampsia All participants will receive study agent nicotinamide: 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday	Nicotinamide - Healthy Pregnant All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning	Nicotinamide - Healthy Non-Pregnant All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning
Overall Study Delivery due to maternal condition	2	0	0

Baseline Characteristics

Study of Nicotinamide in Early Onset Preeclampsia

Baseline characteristics by cohort

Measure	Nicotinamide - Pre-eclampsia n=9 Participants All participants will receive study agent nicotinamide: 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday	Nicotinamide - Healthy Pregnant n=6 Participants All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning	Nicotinamide - Healthy Non-Pregnant n=6 Participants All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning	Total n=21 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	21 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	21 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	16 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	14 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment United States	9 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	21 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, 48 hours

Blood pressure (mmHg) will be used to observe the effect of nicotinamide. The highest MAP (defined as the highest MAP within the 24 hour period prior to the administration of study agent) and the highest MAP through 24 hours after study drug administration.

Outcome measures

Measure	Nicotinamide - Pre-eclampsia n=9 Participants All participants will receive study agent nicotinamide: 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday	Nicotinamide - Healthy Pregnant n=6 Participants All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning	Nicotinamide - Healthy Non-Pregnant n=6 Participants All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning
Change in Mean Arterial Blood Pressure (MAP)	0 mmHg Standard Deviation 9	2 mmHg Standard Deviation 9	4 mmHg Standard Deviation 6

SECONDARY outcome

Timeframe: Within 24 hours of any dose, up to a maximum 4 weeks

Population: Healthy women were not at risk for liver toxicity and therefore were not assessed for ALT.

Outcome measures

Measure	Nicotinamide - Pre-eclampsia n=9 Participants All participants will receive study agent nicotinamide: 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday	Nicotinamide - Healthy Pregnant All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning	Nicotinamide - Healthy Non-Pregnant All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning
Number of Participants With Alanine Aminotransferase (ALT) =/> 3x Upper Limit of Normal (ULN)	0 Participants	—	—

SECONDARY outcome

Timeframe: Within 24 hours of any dose, up to a maximum 4 weeks

Population: Healthy women were not at risk for liver toxicity and therefore were not assessed for AST.

Outcome measures

Measure	Nicotinamide - Pre-eclampsia n=9 Participants All participants will receive study agent nicotinamide: 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday	Nicotinamide - Healthy Pregnant All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning	Nicotinamide - Healthy Non-Pregnant All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning
Number of Participants With Aspartate Aminotransferase (AST) =/> 3x Upper Limit of Normal (ULN)	0 Participants	—	—

SECONDARY outcome

Timeframe: From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks

Maternal side effects are defined as: facial erythema, hives, sore mouth, dry hair, fatigue, flushing, headache, nausea, and heart burn.

Outcome measures

Measure	Nicotinamide - Pre-eclampsia n=9 Participants All participants will receive study agent nicotinamide: 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday	Nicotinamide - Healthy Pregnant n=6 Participants All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning	Nicotinamide - Healthy Non-Pregnant n=6 Participants All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning
Number of Participants With Maternal Side Effects	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks

Outcome measures

Measure	Nicotinamide - Pre-eclampsia n=9 Participants All participants will receive study agent nicotinamide: 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday	Nicotinamide - Healthy Pregnant n=6 Participants All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning	Nicotinamide - Healthy Non-Pregnant n=6 Participants All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning
Percentage of Women Maternal Abdominal Tenderness	0 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks

Outcome measures

Measure	Nicotinamide - Pre-eclampsia n=9 Participants All participants will receive study agent nicotinamide: 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday	Nicotinamide - Healthy Pregnant n=6 Participants All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning	Nicotinamide - Healthy Non-Pregnant n=6 Participants All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning
Percentage of Women With Headache Unrelieved by Oral Analgesics	33 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks

Population: Healthy women were not at risk for anemia and therefore were not assessed for Hematocrit.

Outcome measures

Measure	Nicotinamide - Pre-eclampsia n=9 Participants All participants will receive study agent nicotinamide: 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday	Nicotinamide - Healthy Pregnant All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning	Nicotinamide - Healthy Non-Pregnant All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning
Percentage of Women With Hematocrit Decrease of More Than 3%	44 percentage of participants	—	—

SECONDARY outcome

Timeframe: From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks

Population: Healthy women were not at risk for oliguria and therefore were not assessed for urine output.

Outcome measures

Measure	Nicotinamide - Pre-eclampsia n=9 Participants All participants will receive study agent nicotinamide: 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday	Nicotinamide - Healthy Pregnant All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning	Nicotinamide - Healthy Non-Pregnant All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning
Percentage of Women With Less Than 500 cc Urine Output in 24 Hours	0 percentage of participants	—	—

SECONDARY outcome

Timeframe: From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks

Population: Healthy women were not at risk for placental insufficiency and therefore did not have a non stress test.

A Non Stress Test is a determination of the current well-being of the fetus, as measured by the fetal heart rate. Category I indicates that the fetus is in a state of well-being and is tolerating the intrauterine environment. Category II indicates a fetal heart rate that is showing some signs of distress. In this instance, obstetric providers will try to improve the intrauterine environment to allow the pregnancy to continue. Category III relates to a fetus whose well-being is compromised - usually requiring rapid intervention, ie expedient delivery.

Outcome measures

Measure	Nicotinamide - Pre-eclampsia n=9 Participants All participants will receive study agent nicotinamide: 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday	Nicotinamide - Healthy Pregnant All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning	Nicotinamide - Healthy Non-Pregnant All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning
Percentage of Fetuses With Category III Non Stress Test Results	0 percentage of fetuses	—	—

SECONDARY outcome

Timeframe: From initial administration of study agent until 24 hours post last dose

Population: Data only collected if indicated and performed as part of clinical care. No primary care providers felt this test was indicated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 1 hour post 1000 mg nicotinamide administration on Day 1

Population: Data reported for all participants who had blood collected.

The mean was calculated for each group using blood samples drawn on Day 1 at 1 hour post 1000 mg nicotinamide administration routinely given at 8 a.m. Peak nicotinamide level expected at 1 hour post dose.

Outcome measures

Measure	Nicotinamide - Pre-eclampsia n=6 Participants All participants will receive study agent nicotinamide: 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday	Nicotinamide - Healthy Pregnant n=6 Participants All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning	Nicotinamide - Healthy Non-Pregnant n=6 Participants All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning
Mean Peak Nicotinamide Level	12701.7 ng/mL Standard Deviation 6187.5	13279.7 ng/mL Standard Deviation 970.7	16314.1 ng/mL Standard Deviation 3337.1

SECONDARY outcome

Timeframe: 8 hours after the 8 a.m. 1000 mg nicotimamide administration on Day 1

Population: Data reported for all participants who had blood collected.

The mean was calculated for each group for blood samples drawn on Day 1 8 hours post 1000 mg nicotinamide administration routinely given at 8 a.m. Trough nicotinamide level is measured immediately prior to the next dose.

Outcome measures

Measure	Nicotinamide - Pre-eclampsia n=6 Participants All participants will receive study agent nicotinamide: 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday	Nicotinamide - Healthy Pregnant n=6 Participants All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning	Nicotinamide - Healthy Non-Pregnant n=6 Participants All participants will receive study agent 1000 mg in single dose nicotinamide: 1000 mg nicotinamide in morning
Mean Trough Concentration Nicotinamide Administration	479.2 ng/mL Standard Deviation 967.3	1490.7 ng/mL Standard Deviation 1907.8	1991.2 ng/mL Standard Deviation 2783.6

Adverse Events

Nicotinamide - Pre-eclampsia

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Nicotinamide - Healthy Pregnant

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Nicotinamide - Healthy Non-Pregnant

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Kim Boggess, MD

University of North Carolina at Chapel Hill

Phone: 919-966-1601

Email: kboggess@med.unc.edu

Results disclosure agreements

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