Clinical trial NCT03419364: Study of Nicotinamide in Early Onset Preeclampsia
Official title: Phase II Study of Nicotinamide in Early Onset Preeclampsia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pre-Eclampsia
Pregnancy Related
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2018-02-01
Enrollment: 23
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: All participants will receive study agent. 2.5 gm nicotinamide given orally in 3 divided doses (1000 in morning, 500 in afternoon, 1000 at bedtime).
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: See brief summary above

Eligibility criteria: 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

Primary outcomes:
measure: Change in Mean Arterial Blood Pressure (MAP)
timeFrame: Baseline, 48 hours
Secondary outcomes:
measure: Number of Participants With Alanine Aminotransferase (ALT) =/> 3x Upper Limit of Normal (ULN)
timeFrame: Within 24 hours of any dose, up to a maximum 4 weeks
measure: Number of Participants With Aspartate Aminotransferase (AST) =/> 3x Upper Limit of Normal (ULN)
timeFrame: Within 24 hours of any dose, up to a maximum 4 weeks
measure: Number of Participants With Maternal Side Effects
timeFrame: From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
measure: Percentage of Women Maternal Abdominal Tenderness
timeFrame: From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
measure: Percentage of Women With Headache Unrelieved by Oral Analgesics
timeFrame: From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
measure: Percentage of Women With Hematocrit Decrease of More Than 3%
timeFrame: From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
measure: Percentage of Women With Less Than 500 cc Urine Output in 24 Hours
timeFrame: From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
measure: Percentage of Fetuses With Category III Non Stress Test Results
timeFrame: From initial administration of study agent until 24 hours post last dose, up to a maximum of 4 weeks
measure: Percentage of Fetuses With Biophysical Profile < 6
timeFrame: From initial administration of study agent until 24 hours post last dose
measure: Mean Peak Nicotinamide Level
timeFrame: at 1 hour post 1000 mg nicotinamide administration on Day 1
measure: Mean Trough Concentration Nicotinamide Administration
timeFrame: 8 hours after the 8 a.m. 1000 mg nicotimamide administration on Day 1
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: UNC at Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC_Chapel Hill
name: Kim Boggess, MD
role: PRINCIPAL_INVESTIGATOR
References: