Phase I Study of Nicotinamide for Early Onset Preeclampsia

• Sponsor: University of North Carolina, Chapel Hill (Other)
• Overall Status: Completed
• CT.gov ID: NCT02213094
• Collaborator: North Carolina Translational and Clinical Sciences Institute (Other)
• Enrollment: 10
• Location: 1
• Arms: 2
• Actual Duration (Months): 23
• Patients Per Site Per Month: 0.4

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Pregnancy Induced Hypertension; Superimposed Preeclampsia; Hypertension	Drug: Nicotinamide 500 mg; Drug: Nicotinamide 1000 mg	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: Phase 1 dose escalation studyPhase 1 dose escalation study
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Phase I Study of Nicotinamide for Early Onset Preeclampsia
• Actual Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: Dec 3, 2015
• Actual Study Completion Date: Dec 3, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nicotinamide 500 mg Nicotinamide 500 mg by mouth each morning until delivery or 14 days, whichever occurs first.	Drug: Nicotinamide 500 mg; Nicotinamide 500 mg taken by mouth each morning; Other Names: Vitamin B3 amide
Experimental: Nicotinamide 1000 mg Nicotinamide 1000 mg by mouth each morning until delivery or 14 days, whichever occurs first.	Drug: Nicotinamide 1000 mg; Nicotinamide 1000 mg taken by mouth each morning; Other Names: Vitamin B3 amide

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events [Within 48 hours of dosing]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Maternal age 18-45 years

2. Informed written consent

3. Preeclampsia or new onset hypertension between 24-32 completed weeks' gestation

4. 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;

5. Dating criteria based on menstrual dating confirmed by first or second trimester ultrasound OR second trimester ultrasound if menstrual dating unavailable;

6. Deemed clinically stable by primary clinician and candidate for expectant management (delayed delivery);

7. Maternal liver function tests < 3x ULN

8. Maternal platelet count > 100,000 mm3

9. 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

10. Plan for expectant management until delivery

11. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of North Carolina Women's Hospital	Chapel Hill	North Carolina	United States	27599-7516

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Kim A Boggess, MD, University of North Carolina, Chapel Hill

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT02213094
• Other Study ID Numbers: 13-2203
• First Posted: Aug 11, 2014
• Last Update Posted: Nov 2, 2018
• Last Verified: Mar 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of North Carolina, Chapel Hill: preeclampsia; pregnancy-induced hypertension; nicotinamide
• Additional relevant MeSH terms: Pre-Eclampsia; Hypertension, Pregnancy-Induced; Hypertension; Vitamins; Niacinamide; Niacin; Nicotinic Acids; Vitamin B Complex

Study Results

Participant Flow

Arm/Group Title	Nicotinamide 500 mg	Nicotinamide 1000 mg
Arm/Group 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.
Period Title: Overall Study
STARTED	5	5
COMPLETED	4	5
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Nicotinamide 500 mg	Nicotinamide 1000 mg	Total
Arm/Group 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.	Total of all reporting groups
Overall Participants	5	5	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 100%	5 100%	10 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	5 100%	5 100%	10 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	5 100%	5 100%	10 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nicotinamide 500 mg	Nicotinamide 1000 mg
Arm/Group 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.
Measure Participants	5	5
Number [participants]	2 40%	0 0%

Adverse Events

Time Frame	During study agent administration (up to 14 days)
Arm/Group Title	Nicotinamide 500 mg		Nicotinamide 1000 mg
Arm/Group 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.
All Cause Mortality
	Nicotinamide 500 mg		Nicotinamide 1000 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Serious Adverse Events
	Nicotinamide 500 mg		Nicotinamide 1000 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		0/5 (0%)
Hepatobiliary disorders
Elevated LFTs	1/5 (20%)	1	0/5 (0%)	0
Renal and urinary disorders
Renal failure	1/5 (20%)	1	0/5 (0%)	0
Other (Not Including Serious) Adverse Events
	Nicotinamide 500 mg		Nicotinamide 1000 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.