Phase I Study of Nicotinamide for Early Onset Preeclampsia

Study Overview
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Brief Summary
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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.

Official Title
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Phase I Study of Nicotinamide for Early Onset Preeclampsia

Conditions
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Pregnancy Induced Hypertension, Superimposed Preeclampsia, Hypertension

Intervention / Treatment
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* Drug: Nicotinamide 500 mg
* Drug: Nicotinamide 1000 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Maternal age 18-45 years Informed written consent Preeclampsia or new onset hypertension between 24-32 completed weeks' gestation 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; Dating criteria based on menstrual dating confirmed by first or second trimester ultrasound OR second trimester ultrasound if menstrual dating unavailable; Deemed clinically stable by primary clinician and candidate for expectant management (delayed delivery); Maternal liver function tests < 3x ULN Maternal platelet count > 100,000 mm3 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 Plan for expectant management until delivery Delivery not anticipated within first 48 hours Exclusion Criteria: Preeclampsia < 24 or > 33 weeks' gestation; Suspected fetal structural or chromosomal abnormality; Pre-existing renal disease (creatinine > 1.5 mg/dL) Pre-existing vascular disease (systemic lupus; cardiac disease;) Plan for delivery within 48 hours Any pre-existing medical condition that would increase risk for liver toxicity (e.g. hepatitis B or C; HIV) Evidence of cerebral dysfunction (seizures; cerebral edema on CT/MRI; headache unresolved with oral analgesics) Pulmonary edema HELLP (hemolysis, elevated liver enzymes, low platelets syndrome) Evidence of liver dysfunction (LFTs > 3x ULN) Thrombocytopenia (platelets < 100,000 mm3) Evidence of fetal compromise: EFW(estimated fetal weight) < 5th percentile; BPP < 6; absent or reverse diastolic UA blood flow; 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Phase 1 dose escalation study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nicotinamide 500 mg<br>Nicotinamide 500 mg by mouth each morning until delivery or 14 days, whichever occurs first. | Drug: Nicotinamide 500 mg<br>* Nicotinamide 500 mg taken by mouth each morning<br>* Other names: Vitamin B3 amide;|
| Experimental: Nicotinamide 1000 mg<br>Nicotinamide 1000 mg by mouth each morning until delivery or 14 days, whichever occurs first. | Drug: Nicotinamide 1000 mg<br>* Nicotinamide 1000 mg taken by mouth each morning<br>* Other names: Vitamin B3 amide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Specific adverse events were Maternal liver toxicity, defined as > 3x ULN of ALT(Alanine amniotransferase) or AST (Aspartate amniotransferase), maternal report of side effects, and fetal adverse effects. | Within 48 hours of dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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preeclampsia, pregnancy-induced hypertension, nicotinamide