Phase I Study of Nicotinamide for Early Onset Preeclampsia
Phase I Study of Nicotinamide for Early Onset Preeclampsia
This is a Phase I study of vitamin B3-amide (nicotinamide) dietary supplementation in
 pregnant women with early onset preeclampsia. The investigators will enroll 10 pregnant women
 at 24-32 weeks' gestation with the diagnosis of preeclampsia. If the woman is anticipated to
 remain undelivered for 48 hours after diagnosis she will receive vitamin B3-amide, 500 mg/day
 given in the morning (n=5) or 1000 mg given in the morning (n=5), continuing until delivery
 or for 14 days, whichever occurs first. Maternal blood will be collected at baseline and
 twice a day on days 1, 3, and 7 of nicotinamide administration to measure nicotinamide
 metabolites, The objectives of this Phase I study are to to test safety of nicotinamide.
Inclusion Criteria:

 1. Maternal age 18-45 years

 2. Informed written consent

 3. Preeclampsia or new onset hypertension between 24-32 completed weeks' gestation

 1. Hypertensive complications of pregnancy defined as new onset systolic BP > 140 mm
 Hg and/or diastolic BP > 90 mm Hg on two occasions 6 hours apart; OR > 300 mg
 proteinuria on 24 hour urine collection OR urine P/C ratio >0.3;

 2. Dating criteria based on menstrual dating confirmed by first or second trimester
 ultrasound OR second trimester ultrasound if menstrual dating unavailable;

 3. Deemed clinically stable by primary clinician and candidate for expectant
 management (delayed delivery);

 4. Maternal liver function tests < 3x ULN

 5. Maternal platelet count > 100,000 mm3

 6. Fetal well-being established by estimated fetal weight > 5th %tile; normal amniotic
 fluid volume (MVP > 2 cm); normal Umbilical Artery Dopplers; AND reactive
 NST(non-stress test) or BPP (biophysical profile) > 6

 7. Plan for expectant management until delivery

 8. Delivery not anticipated within first 48 hours

 Exclusion Criteria:

 1. Preeclampsia < 24 or > 33 weeks' gestation;

 2. Suspected fetal structural or chromosomal abnormality;

 3. Pre-existing renal disease (creatinine > 1.5 mg/dL)

 4. Pre-existing vascular disease (systemic lupus; cardiac disease;)

 5. Plan for delivery within 48 hours

 6. Any pre-existing medical condition that would increase risk for liver toxicity (e.g.
 hepatitis B or C; HIV)

 7. Evidence of cerebral dysfunction (seizures; cerebral edema on CT/MRI; headache
 unresolved with oral analgesics)

 8. Pulmonary edema

 9. HELLP (hemolysis, elevated liver enzymes, low platelets syndrome)

 10. Evidence of liver dysfunction (LFTs > 3x ULN)

 11. Thrombocytopenia (platelets < 100,000 mm3)

 12. Evidence of fetal compromise: EFW(estimated fetal weight) < 5th percentile; BPP < 6;
 absent or reverse diastolic UA blood flow; oligohydramnios (MVP < 2 cm)

 13. Placental abruption defined as unexplained vaginal bleeding

 14. Preterm labor defined as regular contractions and cervical change

 15. Any condition deemed by the investigator to be a risk to mother or fetus in completion
 of the study

 16. Any condition deemed by the investigator to require delivery within 48 hours