Clinical trial NCT02213094: Phase I Study of Nicotinamide for Early Onset Preeclampsia
Official title: Phase I Study of Nicotinamide for Early Onset Preeclampsia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pregnancy Induced Hypertension
Superimposed Preeclampsia
Hypertension
Keywords: preeclampsia
pregnancy-induced hypertension
nicotinamide
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: North Carolina Translational and Clinical Sciences Institute
First posted: 2014-08-11
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Phase 1 dose escalation study
Primary purpose: OTHER

Brief 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

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Within 48 hours of dosing
Secondary outcomes:
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina Women's Hospital
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Kim A Boggess, MD
role: PRINCIPAL_INVESTIGATOR
References: