Phase I Study of Nicotinamide for Early Onset Preeclampsia

NCT02213094 | Completed Phase 1 Results DMC

• 1 other identifier: 13-2203
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Pregnancy Induced Hypertension; Superimposed Preeclampsia; Hypertension

Keywords

preeclampsia; pregnancy-induced hypertension; nicotinamide

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Nicotinamide 500 mg

EXPERIMENTAL

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

Drug: Nicotinamide 500 mg

Nicotinamide 1000 mg

EXPERIMENTAL

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

Drug: Nicotinamide 1000 mg

Interventions

Nicotinamide 500 mg DRUG

Nicotinamide 500 mg taken by mouth each morning

Also known as: Vitamin B3 amide

Nicotinamide 500 mg

Nicotinamide 1000 mg DRUG

Nicotinamide 1000 mg taken by mouth each morning

Also known as: Vitamin B3 amide

Nicotinamide 1000 mg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• North Carolina Translational and Clinical Sciences Institute: collaborator

Study Sites (1)

University of North Carolina Women's Hospital

Chapel Hill, North Carolina, 27599-7516, United States

Location

MeSH Terms

Conditions

Hypertension, Pregnancy-Induced; Hypertension; Pre-Eclampsia

Interventions

Niacinamide

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Kim Boggess MD Principal Investigator
• Organization: UNC at Chapel Hill

kboggess@med.unc.edu

919-966-1601

Study Officials

• Kim A Boggess, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 1 dose escalation study

Study Record Dates

• First Submitted: August 7, 2014
• First Posted: August 11, 2014
• Study Start: January 1, 2014
• Primary Completion: December 3, 2015
• Study Completion: December 3, 2015
• Last Updated: November 2, 2018
• Results First Posted: November 2, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)