Study of Nicotinamide in Early Onset Preeclampsia
Condition: Pre-Eclampsia; Pregnancy Related
MeSH terms: Pre-Eclampsia; Eclampsia
Intervention: nicotinamide
Intervention description: 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday
Intervention MeSH terms: Niacinamide; Niacin; Nicotinic Acids
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Intervention 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)
Enrollment: 23.0
Sex: Female
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

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.
    

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