Arginine + Citrulline as a Supplement for Weight Gain in Fetus With a Decrease in Their Growth Curve

Fetal Growth Retardation Clinical Trial

Official title:

Efficacy L-arginine + L-citrulline as a Dietary Supplement vs Placebo for Weight Gain in Fetus With a Decrease in Their Growth Curve in the Third Trimester of Pregnancy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05029778
• Other study ID #: 097/20
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: October 20, 2021
• Est. completion date: January 20, 2024

Study information

• Verified date: August 2021
• Source: Hospital Civil de Guadalajara
• Contact: Jorge Bravo Rubio, Dr
• Phone: 3221186759
• Email: naranjo125[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Introduction:

The high incidence of intrauterine growth restriction is a public health problem; in this pathology, newborns present weight below the 10th percentile, this implies an increase in morbidity in the short term (complications due to hypoxia) and long term (pathologies typical of Fetal Programming) as well as the cost of health services. L-arginine at different doses has been used for some pathologies such as preeclampsia with controversial results. Authors have mentioned that the joint administration of l-citrulline can increase the efficacy of l-arginine. A stunted fetus is a challenge for the fetal physician; due to the complexity of the follow-up, but above all to determine the moment for the termination of the pregnancy. Finding some treatment to promote weight gain would improve the short- and long-term expectations of these infants.

General objective To determine the efficacy of L-arginine + L-Citrulline (3 / 2g) every 24 hours, in fetuses with a decrease in their growth curve in the third trimester of pregnancy.

Material and methods Clinical trial, parallel, controlled, randomized simple, Double blind. Two groups of pregnant women will be carried out in the third trimester; fetus with a decrease in its growth curve, percentile> 10 and <25 for gestation age, they will be given an informed consent letter and they will be randomized (double blind), they will proceed to give intervention (L-arginine + Citrin (3 / 2 g) every 24 hours Vs placebo), a follow-up will be carried out every two weeks, where the weight and growth curve will be calculated in percentile, until the resolution of the pregnancy and data will be taken from the perinatal results in both groups.

Statistic analysis Medics of central tendency will be calculated and Chi squared will be applied for qualitative variables, T of student for qualitative variables and it is considered P <0.005.

Description:

50 patients with a pregnancy of more than 26 weeks of gestation, 25 with intervention and 25 control will be included; in which the fetus is between 10 and 25th percentile . It will be carried out in the obstetric service of the old civil hospital, with a double-blind randomization.

Evaluations will be carried out every two weeks where the fetal weight, umbilical artery Doppler, middle cerebral artery, venous duct, uterine arteries, amniotic fluid, placenta will be evaluated.

The assessment will be made until birth, from where the birth weight, height, Apgar, Capurro score, characteristics and placental weight, approximate bleeding will be collected.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 41
• Est. completion date: January 20, 2024
• Est. primary completion date: October 20, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Pregnancy with a single fetus

• Patient over 18 years of age

• Patient under 35 years of age

• Pregnancy greater than 25 weeks' gestation confirmed by first trimester ultrasound or reliable last period

• Fetus with decrease or flattening of its growth curve by ultrasound (P> 10 and <25)

• Apparently healthy fetus

• Fetus without Doppler alterations in any of its blood vessels (Venous Ductus, Cerebral Artery medial, Umbilical Artery .

Exclusion Criteria:

• Fetus diagnosed with a malformation

• Fetus diagnosed with a syndrome or chromosomopathy

• Fetus below the 10th percentile for gestational age by ultrasound

• Mother with Type 1, Type 2 or Gestational Diabetes mellitus.

• Chronic maternal hypertension

• Preeclampsia with data of severity or early onset

• Aspirin intake (100-150 mg a day from the first trimester of pregnancy)

• Fetus with a poor ultrasonographic window for evaluation.

• Mother with BMI <18.5 prior to pregnancy

• Maternal BMI> 30

• Known allergy to treatment

• Non-reassuring fetal state.

• Abnormal placental insertion.

• Patient with renal insufficiency, LUPUS or Antiphospholipid syndrome

Related Conditions & MeSH terms

• Fetal Growth Retardation
• Weight Gain

Intervention

Dietary Supplement:
• L-arginine 3g + L-Citruline 2 g
receive L-arginine 3g + l-Citruline 2 g PO, for 24 h, until birth.

Drug:
• Placebo
receive placebo 3g PO, for 24 h, until birth.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Civil de Guadalajara

References & Publications (11)

Ananth CV, Vintzileos AM. Distinguishing pathological from constitutional small for gestational age births in population-based studies. Early Hum Dev. 2009 Oct;85(10):653-8. doi: 10.1016/j.earlhumdev.2009.09.004. Epub 2009 Sep 27. — View Citation

Barker DJ, Osmond C, Kajantie E, Eriksson JG. Growth and chronic disease: findings in the Helsinki Birth Cohort. Ann Hum Biol. 2009 Sep-Oct;36(5):445-58. doi: 10.1080/03014460902980295. — View Citation

Bourdon A, Parnet P, Nowak C, Tran NT, Winer N, Darmaun D. L-Citrulline Supplementation Enhances Fetal Growth and Protein Synthesis in Rats with Intrauterine Growth Restriction. J Nutr. 2016 Mar;146(3):532-41. doi: 10.3945/jn.115.221267. Epub 2016 Feb 10. — View Citation

Bujold E, Morency AM, Roberge S, Lacasse Y, Forest JC, Giguère Y. Acetylsalicylic acid for the prevention of preeclampsia and intra-uterine growth restriction in women with abnormal uterine artery Doppler: a systematic review and meta-analysis. J Obstet G — View Citation

Byrne BM, Howard RB, Morrow RJ, Whiteley KJ, Adamson SL. Role of the L-arginine nitric oxide pathway in hypoxic fetoplacental vasoconstriction. Placenta. 1997 Nov;18(8):627-34. — View Citation

Camarena Pulido EE, García Benavides L, Panduro Barón JG, Pascoe Gonzalez S, Madrigal Saray AJ, García Padilla FE, Totsuka Sutto SE. Efficacy of L-arginine for preventing preeclampsia in high-risk pregnancies: A double-blind, randomized, clinical trial. H — View Citation

Chen J, Gong X, Chen P, Luo K, Zhang X. Effect of L-arginine and sildenafil citrate on intrauterine growth restriction fetuses: a meta-analysis. BMC Pregnancy Childbirth. 2016 Aug 16;16:225. doi: 10.1186/s12884-016-1009-6. Review. — View Citation

Colella M, Frérot A, Novais ARB, Baud O. Neonatal and Long-Term Consequences of Fetal Growth Restriction. Curr Pediatr Rev. 2018;14(4):212-218. doi: 10.2174/1573396314666180712114531. Review. — View Citation

Cottrell E, Tropea T, Ormesher L, Greenwood S, Wareing M, Johnstone E, Myers J, Sibley C. Dietary interventions for fetal growth restriction - therapeutic potential of dietary nitrate supplementation in pregnancy. J Physiol. 2017 Aug 1;595(15):5095-5102. — View Citation

Crispi F, Miranda J, Gratacós E. Long-term cardiovascular consequences of fetal growth restriction: biology, clinical implications, and opportunities for prevention of adult disease. Am J Obstet Gynecol. 2018 Feb;218(2S):S869-S879. doi: 10.1016/j.ajog.201 — View Citation

Dover GJ. The Barker hypothesis: how pediatricans will diagnose and prevent common adult-onset diseases. Trans Am Clin Climatol Assoc. 2009;120:199-207. Review. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fetal Growth	fetal weight gain	10 weeks