Back to resultsStudy of Nicotinamide in Early Onset Preeclampsia
Primary Purpose
Pre-Eclampsia, Pregnancy Related
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
nicotinamide
Sponsored by
About this trial
This is an interventional treatment trial for Pre-Eclampsia
Eligibility Criteria
Diagnosis and Inclusion Criteria
- Maternal age 18-55 years
- Singleton pregnancy with no known fetal anomalies
Early-onset preeclampsia OR early-onset severe gestational hypertension defined as:
- Early-onset: between 24 weeks 0 days and -33 weeks 3 days, based on menstrual dating confirmed by first or second trimester ultrasound OR second trimester ultrasound if menstrual dating unavailable;
- Preeclampsia:
- New onset hypertension and proteinuria, with systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg on two occasions 6 hours apart and > 300 mg proteinuria on 24 hour urine collection OR urine P/C ratio >0.3;
- New onset hypertension and NO proteinuria, with systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg on two occasions 6 hours apart and one or more of the following: serum creatinine >1.1 mg/dL or doubling from baseline ,or central nervous system symptoms or visual changes
Severe preeclampsia defined as new onset systolic BP > 160 mm Hg and/or diastolic BP > 105 with proteinuria as above or or without proteinuria and one or more of the following criteria listed above
- Candidate for expectant management for at least 48 hours
- Deemed clinically stable by primary clinician and candidate for expectant management (delayed delivery) for at least 48 hours;
- Maternal liver function tests < 2x ULN
- Maternal platelet count > 100,000 mm³
- Planned expectant management
- Pre-existing medical diseases such as hypertension, diabetes, endocrine disorders, gastrointestinal diseases, are well controlled
- Fetal well-being established by estimated fetal weight > 5th %tile; normal amniotic fluid volume (MVP > 2 cm); normal Umbilical Artery (UA) Dopplers; or reactive Non Stress Test (NST) or Biophysical Profile (BPP) > 6
- Delivery not anticipated within 48 hours of enrollment
Exclusion Criteria
- Pre-existing renal disease (creatinine > 1.5 mg/dL)
- Any pre-existing medical condition that would increase risk for liver toxicity (e.g. hepatitis B or C; HIV; Isoniazid (INH) use)
- Eclampsia; cerebral edema on CT/MRI; headache unrelieved by analgesics
- Evidence of liver dysfunction (LFTs > 2x ULN)
- Thrombocytopenia (platelets < 100,000 mm³)
- Pulmonary edema
- HELLP syndrome
- Evidence of fetal compromise: Estimated Fetal Weight (EFW) < 5th percentile; or BPP < 6; or absent or reverse diastolic UA blood flow; or oligohydramnios (MVP < 2 cm)
- Placental abruption defined as unexplained vaginal bleeding
- Preterm labor defined as regular contractions and cervical change
- Any condition deemed by the investigator to be a risk to mother or fetus in completion of the study
- Any condition deemed by the investigator to require delivery within 48 hours
Sites / Locations
- UNC at Chapel Hill
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Nicotinamide - pre-eclampsia
Nicotinamide - healthy pregnant
Healthy Non-Pregnant
Arm Description
All participants will receive study agent
All participants will receive study agent 1000mg in single dose
All participants will receive study agent 1000mg in single dose
Outcomes
Primary Outcome Measures
Change in Mean Arterial Blood Pressure (MAP)
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.
Secondary Outcome Measures
Number of Participants With Alanine Aminotransferase (ALT) =/> 3x Upper Limit of Normal (ULN)
Number of Participants With Aspartate Aminotransferase (AST) =/> 3x Upper Limit of Normal (ULN)
Number of Participants With Maternal Side Effects
Maternal side effects are defined as: facial erythema, hives, sore mouth, dry hair, fatigue, flushing, headache, nausea, and heart burn.
Percentage of Women Maternal Abdominal Tenderness
Percentage of Women With Headache Unrelieved by Oral Analgesics
Percentage of Women With Hematocrit Decrease of More Than 3%
Percentage of Women With Less Than 500 cc Urine Output in 24 Hours
Percentage of Fetuses With Category III Non Stress Test Results
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.
Percentage of Fetuses With Biophysical Profile < 6
Mean Peak Nicotinamide Level
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.
Mean Trough Concentration Nicotinamide Administration
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.
Full Information
NCT ID
NCT03419364
First Posted
January 26, 2018
Last Updated
August 16, 2022
Sponsor
University of North Carolina, Chapel Hill
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1. Study Identification
Unique Protocol Identification Number
NCT03419364
Brief Title
Study of Nicotinamide in Early Onset Preeclampsia
Official Title
Phase II Study of Nicotinamide in Early Onset Preeclampsia
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
November 1, 2017 (Actual)
Primary Completion Date
August 31, 2021 (Actual)
Study Completion Date
August 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Phase II Study of 2.5 gm of nicotinamide, given daily in 3 divided doses, to measure effect on maternal blood pressure in women with early onset preeclampsia and to determine peak and trough levels of nicotinamide. We will compare peak and trough levels in healthy non-pregnant and healthy pregnant participants.
Detailed Description
See brief summary above
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pre-Eclampsia, Pregnancy Related
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
All participants will receive study agent. 2.5 gm nicotinamide given orally in 3 divided doses (1000 in morning, 500 in afternoon, 1000 at bedtime).
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nicotinamide - pre-eclampsia
Arm Type
Experimental
Arm Description
All participants will receive study agent
Arm Title
Nicotinamide - healthy pregnant
Arm Type
Experimental
Arm Description
All participants will receive study agent 1000mg in single dose
Arm Title
Healthy Non-Pregnant
Arm Type
Experimental
Arm Description
All participants will receive study agent 1000mg in single dose
Intervention Type
Drug
Intervention Name(s)
nicotinamide
Other Intervention Name(s)
niacinamide
Intervention Description
2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday
Primary Outcome Measure Information:
Title
Change in Mean Arterial Blood Pressure (MAP)
Description
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.
Time Frame
Baseline, 48 hours
Secondary Outcome Measure Information:
Title
Number of Participants With Alanine Aminotransferase (ALT) =/> 3x Upper Limit of Normal (ULN)
Time Frame
Within 24 hours of any dose, up to a maximum 4 weeks
Title
Number of Participants With Aspartate Aminotransferase (AST) =/> 3x Upper Limit of Normal (ULN)
Time Frame
Within 24 hours of any dose, up to a maximum 4 weeks
Title
Number of Participants With Maternal Side Effects
Description
Maternal side effects are defined as: facial erythema, hives, sore mouth, dry hair, fatigue, flushing, headache, nausea, and heart burn.
Time Frame
From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Title
Percentage of Women Maternal Abdominal Tenderness
Time Frame
From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Title
Percentage of Women With Headache Unrelieved by Oral Analgesics
Time Frame
From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Title
Percentage of Women With Hematocrit Decrease of More Than 3%
Time Frame
From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Title
Percentage of Women With Less Than 500 cc Urine Output in 24 Hours
Time Frame
From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Title
Percentage of Fetuses With Category III Non Stress Test Results
Description
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.
Time Frame
From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Title
Percentage of Fetuses With Biophysical Profile < 6
Time Frame
From initial administration of study agent until 24 hours post last dose
Title
Mean Peak Nicotinamide Level
Description
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.
Time Frame
at 1 hour post 1000 mg nicotinamide administration on Day 1
Title
Mean Trough Concentration Nicotinamide Administration
Description
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.
Time Frame
8 hours after the 8 a.m. 1000 mg nicotimamide administration on Day 1
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Study of pregnant and non-pregnant women only
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Diagnosis and Inclusion Criteria
Maternal age 18-55 years
Singleton pregnancy with no known fetal anomalies
Early-onset preeclampsia OR early-onset severe gestational hypertension defined as:
Early-onset: between 24 weeks 0 days and -33 weeks 3 days, based on menstrual dating confirmed by first or second trimester ultrasound OR second trimester ultrasound if menstrual dating unavailable;
Preeclampsia:
New onset hypertension and proteinuria, with systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg on two occasions 6 hours apart and > 300 mg proteinuria on 24 hour urine collection OR urine P/C ratio >0.3;
New onset hypertension and NO proteinuria, with systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg on two occasions 6 hours apart and one or more of the following: serum creatinine >1.1 mg/dL or doubling from baseline ,or central nervous system symptoms or visual changes
Severe preeclampsia defined as new onset systolic BP > 160 mm Hg and/or diastolic BP > 105 with proteinuria as above or or without proteinuria and one or more of the following criteria listed above
Candidate for expectant management for at least 48 hours
Deemed clinically stable by primary clinician and candidate for expectant management (delayed delivery) for at least 48 hours;
Maternal liver function tests < 2x ULN
Maternal platelet count > 100,000 mm³
Planned expectant management
Pre-existing medical diseases such as hypertension, diabetes, endocrine disorders, gastrointestinal diseases, are well controlled
Fetal well-being established by estimated fetal weight > 5th %tile; normal amniotic fluid volume (MVP > 2 cm); normal Umbilical Artery (UA) Dopplers; or reactive Non Stress Test (NST) or Biophysical Profile (BPP) > 6
Delivery not anticipated within 48 hours of enrollment
Exclusion Criteria
Pre-existing renal disease (creatinine > 1.5 mg/dL)
Any pre-existing medical condition that would increase risk for liver toxicity (e.g. hepatitis B or C; HIV; Isoniazid (INH) use)
Eclampsia; cerebral edema on CT/MRI; headache unrelieved by analgesics
Evidence of liver dysfunction (LFTs > 2x ULN)
Thrombocytopenia (platelets < 100,000 mm³)
Pulmonary edema
HELLP syndrome
Evidence of fetal compromise: Estimated Fetal Weight (EFW) < 5th percentile; or BPP < 6; or absent or reverse diastolic UA blood flow; or oligohydramnios (MVP < 2 cm)
Placental abruption defined as unexplained vaginal bleeding
Preterm labor defined as regular contractions and cervical change
Any condition deemed by the investigator to be a risk to mother or fetus in completion of the study
Any condition deemed by the investigator to require delivery within 48 hours
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kim Boggess, MD
Organizational Affiliation
UNC_Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
UNC at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Study of Nicotinamide in Early Onset Preeclampsia
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