Study of Nicotinamide in Early Onset Preeclampsia

Phase II Study of Nicotinamide in Early Onset Preeclampsia

Phase II Study of 2.5 gm of nicotinamide, given daily in 3 divided doses, to measure effect on maternal blood pressure in women with early onset preeclampsia and to determine peak and trough levels of nicotinamide. We will compare peak and trough levels in healthy non-pregnant and healthy pregnant participants.

Study Overview

• Status: Completed
• Conditions: Pregnancy Related; Pre-Eclampsia
• Intervention / Treatment: Drug: nicotinamide

Detailed Description

See brief summary above

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC at Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Diagnosis and Inclusion Criteria

• Maternal age 18-55 years
• Singleton pregnancy with no known fetal anomalies

• Early-onset preeclampsia OR early-onset severe gestational hypertension defined as:

  • Early-onset: between 24 weeks 0 days and -33 weeks 3 days, based on menstrual dating confirmed by first or second trimester ultrasound OR second trimester ultrasound if menstrual dating unavailable;
  • Preeclampsia:
• New onset hypertension and proteinuria, with systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg on two occasions 6 hours apart and > 300 mg proteinuria on 24 hour urine collection OR urine P/C ratio >0.3;
• New onset hypertension and NO proteinuria, with systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg on two occasions 6 hours apart and one or more of the following: serum creatinine >1.1 mg/dL or doubling from baseline ,or central nervous system symptoms or visual changes

• Severe preeclampsia defined as new onset systolic BP > 160 mm Hg and/or diastolic BP > 105 with proteinuria as above or or without proteinuria and one or more of the following criteria listed above

  • Candidate for expectant management for at least 48 hours
  • Deemed clinically stable by primary clinician and candidate for expectant management (delayed delivery) for at least 48 hours;
• Maternal liver function tests < 2x ULN
• Maternal platelet count > 100,000 mm³
• Planned expectant management
• Pre-existing medical diseases such as hypertension, diabetes, endocrine disorders, gastrointestinal diseases, are well controlled
• Fetal well-being established by estimated fetal weight > 5th %tile; normal amniotic fluid volume (MVP > 2 cm); normal Umbilical Artery (UA) Dopplers; or reactive Non Stress Test (NST) or Biophysical Profile (BPP) > 6
• Delivery not anticipated within 48 hours of enrollment

Exclusion Criteria

• Pre-existing renal disease (creatinine > 1.5 mg/dL)
• Any pre-existing medical condition that would increase risk for liver toxicity (e.g. hepatitis B or C; HIV; Isoniazid (INH) use)
• Eclampsia; cerebral edema on CT/MRI; headache unrelieved by analgesics
• Evidence of liver dysfunction (LFTs > 2x ULN)
• Thrombocytopenia (platelets < 100,000 mm³)
• Pulmonary edema
• HELLP syndrome
• Evidence of fetal compromise: Estimated Fetal Weight (EFW) < 5th percentile; or BPP < 6; or absent or reverse diastolic UA blood flow; or 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nicotinamide - pre-eclampsia; All participants will receive study agent	Drug: nicotinamide; 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday; Other Names: niacinamide
Experimental: Nicotinamide - healthy pregnant; All participants will receive study agent 1000mg in single dose	Drug: nicotinamide; 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday; Other Names: niacinamide
Experimental: Healthy Non-Pregnant; All participants will receive study agent 1000mg in single dose	Drug: nicotinamide; 2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday; Other Names: niacinamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Arterial Blood Pressure (MAP)	Blood pressure (mmHg) will be used to observe the effect of nicotinamide. The highest MAP (defined as the highest MAP within the 24 hour period prior to the administration of study agent) and the highest MAP through 24 hours after study drug administration.	Baseline, 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Alanine Aminotransferase (ALT) =/> 3x Upper Limit of Normal (ULN)		Within 24 hours of any dose, up to a maximum 4 weeks
Number of Participants With Aspartate Aminotransferase (AST) =/> 3x Upper Limit of Normal (ULN)		Within 24 hours of any dose, up to a maximum 4 weeks
Number of Participants With Maternal Side Effects	Maternal side effects are defined as: facial erythema, hives, sore mouth, dry hair, fatigue, flushing, headache, nausea, and heart burn.	From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Percentage of Women Maternal Abdominal Tenderness		From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Percentage of Women With Headache Unrelieved by Oral Analgesics		From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Percentage of Women With Hematocrit Decrease of More Than 3%		From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Percentage of Women With Less Than 500 cc Urine Output in 24 Hours		From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Percentage of Fetuses With Category III Non Stress Test Results	A Non Stress Test is a determination of the current well-being of the fetus, as measured by the fetal heart rate. Category I indicates that the fetus is in a state of well-being and is tolerating the intrauterine environment. Category II indicates a fetal heart rate that is showing some signs of distress. In this instance, obstetric providers will try to improve the intrauterine environment to allow the pregnancy to continue. Category III relates to a fetus whose well-being is compromised - usually requiring rapid intervention, ie expedient delivery.	From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
Percentage of Fetuses With Biophysical Profile < 6		From initial administration of study agent until 24 hours post last dose
Mean Peak Nicotinamide Level	The mean was calculated for each group using blood samples drawn on Day 1 at 1 hour post 1000 mg nicotinamide administration routinely given at 8 a.m. Peak nicotinamide level expected at 1 hour post dose.	at 1 hour post 1000 mg nicotinamide administration on Day 1
Mean Trough Concentration Nicotinamide Administration	The mean was calculated for each group for blood samples drawn on Day 1 8 hours post 1000 mg nicotinamide administration routinely given at 8 a.m. Trough nicotinamide level is measured immediately prior to the next dose.	8 hours after the 8 a.m. 1000 mg nicotimamide administration on Day 1

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Kim Boggess, MD, UNC_Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Actual): August 31, 2021
• Study Completion (Actual): August 31, 2021

Study Registration Dates

• First Submitted: January 26, 2018
• First Submitted That Met QC Criteria: January 31, 2018
• First Posted (Actual): February 1, 2018

Study Record Updates

• Last Update Posted (Actual): September 8, 2022
• Last Update Submitted That Met QC Criteria: August 16, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Eclampsia; Pre-Eclampsia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: 17-0693; 1R03HD092370-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No