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Phase I Study of Nicotinamide for Early Onset Preeclampsia

Primary Purpose

Pregnancy Induced Hypertension, Superimposed Preeclampsia, Hypertension

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nicotinamide 500 mg
Nicotinamide 1000 mg
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Pregnancy Induced Hypertension focused on measuring preeclampsia, pregnancy-induced hypertension, nicotinamide

Eligibility Criteria

18 Years - 45 Years (Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of North Carolina Women's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Nicotinamide 500 mg

Nicotinamide 1000 mg

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
August 7, 2014
Last Updated
March 15, 2018
Sponsor
University of North Carolina, Chapel Hill
Collaborators
North Carolina Translational and Clinical Sciences Institute
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1. Study Identification

Unique Protocol Identification Number
NCT02213094
Brief Title
Phase I Study of Nicotinamide for Early Onset Preeclampsia
Official Title
Phase I Study of Nicotinamide for Early Onset Preeclampsia
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
January 1, 2014 (Actual)
Primary Completion Date
December 3, 2015 (Actual)
Study Completion Date
December 3, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
North Carolina Translational and Clinical Sciences Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pregnancy Induced Hypertension, Superimposed Preeclampsia, Hypertension
Keywords
preeclampsia, pregnancy-induced hypertension, nicotinamide

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Phase 1 dose escalation study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nicotinamide 500 mg
Arm Type
Experimental
Arm Description
Nicotinamide 500 mg by mouth each morning until delivery or 14 days, whichever occurs first.
Arm Title
Nicotinamide 1000 mg
Arm Type
Experimental
Arm Description
Nicotinamide 1000 mg by mouth each morning until delivery or 14 days, whichever occurs first.
Intervention Type
Drug
Intervention Name(s)
Nicotinamide 500 mg
Other Intervention Name(s)
Vitamin B3 amide
Intervention Description
Nicotinamide 500 mg taken by mouth each morning
Intervention Type
Drug
Intervention Name(s)
Nicotinamide 1000 mg
Other Intervention Name(s)
Vitamin B3 amide
Intervention Description
Nicotinamide 1000 mg taken by mouth each morning
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events
Description
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

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 Any condition deemed by the investigator to require delivery within 48 hours
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kim A Boggess, MD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of North Carolina Women's Hospital
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7516
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Phase I Study of Nicotinamide for Early Onset Preeclampsia

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