phase i study of nicotinamide for early onset preeclampsia

Conditions: Pregnancy Induced Hypertension; Superimposed Preeclampsia; Hypertension

Summary: 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.


Eligibility criteria:
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 \ 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

Keywords: preeclampsia pregnancy-induced hypertension nicotinamide