Study of Nicotinamide in Early Onset Preeclampsia

NCT03419364 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 17-06931R03HD092370-01
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Pre-Eclampsia; Pregnancy Related

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• 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

  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

Study Arms (3)

Nicotinamide - pre-eclampsia

EXPERIMENTAL

All participants will receive study agent

Drug: nicotinamide

Nicotinamide - healthy pregnant

EXPERIMENTAL

All participants will receive study agent 1000mg in single dose

Drug: nicotinamide

Healthy Non-Pregnant

EXPERIMENTAL

All participants will receive study agent 1000mg in single dose

Drug: nicotinamide

Interventions

nicotinamide DRUG

2.5 gm nicotinamide given orally in 3 divided doses: 1000 mg in morning and evening, 500 mg at noon/midday

Also known as: niacinamide

Healthy Non-Pregnant; Nicotinamide - healthy pregnant; Nicotinamide - pre-eclampsia

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: Study of pregnant and non-pregnant women only
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

UNC at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Pre-Eclampsia

Interventions

Niacinamide

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Kim Boggess, MD
• Organization: University of North Carolina at Chapel Hill

kboggess@med.unc.edu

919-966-1601

Study Officials

• Kim Boggess, MD

  UNC_Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: January 26, 2018
• First Posted: February 1, 2018
• Study Start: November 1, 2017
• Primary Completion: August 31, 2021
• Study Completion: August 31, 2021
• Last Updated: September 8, 2022
• Results First Posted: September 8, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)