Phase I Study of Nicotinamide for Early Onset Preeclampsia

Phase 1

Completed

• Conditions: Pregnancy Induced Hypertension; Hypertension; Superimposed Preeclampsia
• Interventions: Drug: Nicotinamide 1000 mg; Drug: Nicotinamide 500 mg

• Registration Number: NCT02213094
• Lead Sponsor: University of North Carolina, Chapel Hill

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-01-01
• Study First Submitted: 2014-08-07
• Study First Submitted QC: 2014-08-08
• Study First Posted: 2014-08-11
• Primary Completion: 2015-12-03
• Study Completion: 2015-12-03
• Results First Submitted: 2018-01-22
• Status Verified: 2018-03
• Results First Submitted QC: 2018-03-15
• Last Update Submitted: 2018-03-15
• Results First Posted: 2018-11-02
• Last Update Posted: 2018-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 10

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nicotinamide 1000 mg	Nicotinamide 1000 mg	Nicotinamide 1000 mg by mouth each morning until delivery or 14 days, whichever occurs first.
Nicotinamide 500 mg	Nicotinamide 500 mg	Nicotinamide 500 mg by mouth each morning until delivery or 14 days, whichever occurs first.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	Within 48 hours of dosing	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.

Trial Locations

Locations (1)

University of North Carolina Women's Hospital; 🇺🇸 Chapel Hill, North Carolina, United States