Study of Nicotinamide in Early Onset Preeclampsia

Pregnancy Related Clinical Trial

Official title:

Phase II Study of Nicotinamide in Early Onset Preeclampsia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03419364
• Other study ID #: 17-0693
• Secondary ID: 1R03HD092370-01
• Status: Completed
• Phase: Phase 2
• Start date: November 1, 2017
• Est. completion date: August 31, 2021

Study information

• Verified date: July 2022
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

See brief summary above

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: August 31, 2021
• Est. primary completion date: August 31, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Eclampsia
• Pre-Eclampsia
• Pregnancy Related

Intervention

Drug:
• nicotinamide
2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday

Locations

Country	Name	City	State
United States	UNC at Chapel Hill	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, 48 hours
Secondary	Number of Participants With Alanine Aminotransferase (ALT) =/> 3x Upper Limit of Normal (ULN)		Within 24 hours of any dose, up to a maximum 4 weeks
Secondary	Number of Participants With Aspartate Aminotransferase (AST) =/> 3x Upper Limit of Normal (ULN)		Within 24 hours of any dose, up to a maximum 4 weeks
Secondary	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.	From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Secondary	Percentage of Women Maternal Abdominal Tenderness		From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Secondary	Percentage of Women With Headache Unrelieved by Oral Analgesics		From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Secondary	Percentage of Women With Hematocrit Decrease of More Than 3%		From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Secondary	Percentage of Women With Less Than 500 cc Urine Output in 24 Hours		From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Secondary	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.	From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Secondary	Percentage of Fetuses With Biophysical Profile < 6		From initial administration of study agent until 24 hours post last dose
Secondary	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.	at 1 hour post 1000 mg nicotinamide administration on Day 1
Secondary	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.	8 hours after the 8 a.m. 1000 mg nicotimamide administration on Day 1