Phase I Study of Nicotinamide for Early Onset Preeclampsia

Hypertension Clinical Trial

Official title:

Phase I Study of Nicotinamide for Early Onset Preeclampsia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02213094
• Other study ID #: 13-2203
• Status: Completed
• Phase: Phase 1
• Start date: January 1, 2014
• Est. completion date: December 3, 2015

Study information

• Verified date: March 2018
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 3, 2015
• Est. primary completion date: December 3, 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pregnancy-Induced
• Pre-Eclampsia
• Pregnancy Induced Hypertension
• Superimposed Preeclampsia

Intervention

Drug:
• Nicotinamide 500 mg
Nicotinamide 500 mg taken by mouth each morning
• Nicotinamide 1000 mg
Nicotinamide 1000 mg taken by mouth each morning

Locations

Country	Name	City	State
United States	University of North Carolina Women's Hospital	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	North Carolina Translational and Clinical Sciences Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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