Phase I Study of Nicotinamide for Early Onset Preeclampsia
Condition: Pregnancy Induced Hypertension; Superimposed Preeclampsia; Hypertension
MeSH terms: Pre-Eclampsia; Hypertension, Pregnancy-Induced; Hypertension
Intervention: Nicotinamide 500 mg; Nicotinamide 1000 mg
Intervention description: Nicotinamide 500 mg taken by mouth each morning; Nicotinamide 1000 mg taken by mouth each morning
Intervention MeSH terms: Vitamins; Niacinamide; Niacin; Nicotinic Acids; Vitamin B Complex
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Single Group Assignment
Intervention model description: Phase 1 dose escalation study
Masking: None (Open Label)
Enrollment: 10.0
Sex: Female
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: preeclampsia; pregnancy-induced hypertension; nicotinamide

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 < 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