Hypertension, Pregnancy Induced Hypertension, Superimposed Preeclampsia
Conditions
Keywords
preeclampsia, pregnancy-induced hypertension, nicotinamide
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.
Interventions
DRUGNicotinamide 500 mg
Nicotinamide 500 mg taken by mouth each morning
Nicotinamide 1000 mg taken by mouth each morning
Sponsors
North Carolina Translational and Clinical Sciences Institute
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
Phase 1 dose escalation study
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nicotinamide 500 mg Nicotinamide 500 mg by mouth each morning until delivery or 14 days, whichever occurs first. | 5 |
| Nicotinamide 1000 mg Nicotinamide 1000 mg by mouth each morning until delivery or 14 days, whichever occurs first. | 5 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Nicotinamide 500 mg | Nicotinamide 1000 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 10 Participants |
| Region of Enrollment United States | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 0 / 5 | 0 / 5 |
| serious Total, serious adverse events | 2 / 5 | 0 / 5 |
Outcome results
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.
Time frame: Within 48 hours of dosing
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotinamide 500 mg | Number of Participants With Adverse Events | 2 participants |
| Nicotinamide 1000 mg | Number of Participants With Adverse Events | 0 participants |