Arginine + Citrulline as a Supplement for Weight Gain in Fetus With a Decrease in Their Growth Curve
Primary Purpose
Fetal Growth Retardation
Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
L-arginine 3g + L-Citruline 2 g
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Fetal Growth Retardation focused on measuring L-arginine, l-Citruline, Fetal growth, percentile,
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Experimental L-arginine 3 g and L-citruline 2 g
placebo
Arm Description
Drug: L-arginine 3g and L-citruline 2g, Food supplement, PO , for 24 h, until birth
Placebo 3g ( starch ) PO for 24 h. until birth
Outcomes
Primary Outcome Measures
Fetal Growth
fetal weight gain
Secondary Outcome Measures
Full Information
NCT ID
NCT05029778
First Posted
August 25, 2021
Last Updated
August 27, 2021
Sponsor
Hospital Civil de Guadalajara
1. Study Identification
Unique Protocol Identification Number
NCT05029778
Brief Title
Arginine + Citrulline as a Supplement for Weight Gain in Fetus With a Decrease in Their Growth Curve
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 20, 2021 (Anticipated)
Primary Completion Date
October 20, 2021 (Anticipated)
Study Completion Date
January 20, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hospital Civil de Guadalajara
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fetal Growth Retardation
Keywords
L-arginine, l-Citruline, Fetal growth, percentile,
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Clinical Trial open controlled parallel randomized simple
Masking
ParticipantInvestigator
Masking Description
we don´t know who receives the intervention and who receives the placebo
Allocation
Randomized
Enrollment
41 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental L-arginine 3 g and L-citruline 2 g
Arm Type
Experimental
Arm Description
Drug: L-arginine 3g and L-citruline 2g, Food supplement, PO , for 24 h, until birth
Arm Title
placebo
Arm Type
Experimental
Arm Description
Placebo 3g ( starch ) PO for 24 h. until birth
Intervention Type
Dietary Supplement
Intervention Name(s)
L-arginine 3g + L-Citruline 2 g
Other Intervention Name(s)
L-arginine 3g, L-Citruline 2 g
Intervention Description
receive L-arginine 3g + l-Citruline 2 g PO, for 24 h, until birth.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
receive placebo 3g PO, for 24 h, until birth.
Primary Outcome Measure Information:
Title
Fetal Growth
Description
fetal weight gain
Time Frame
10 weeks
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
single pregnancy in third trimester with fetus between the 10th to 25th percentile
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jorge Bravo Rubio, Dr
Phone
3221186759
Email
naranjo125@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Maria Campechano Ascencio, Dra
Phone
3310233983
Email
angelescampechano@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Milton Omar Guzman Ornelas, Dr.
Organizational Affiliation
University of Guadalajara
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
19768178
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. No abstract available.
Results Reference
background
PubMed Identifier
19786331
Citation
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.
Results Reference
result
PubMed Identifier
19562567
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.
Results Reference
result
PubMed Identifier
26865647
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.
Results Reference
result
PubMed Identifier
19941706
Citation
Bujold E, Morency AM, Roberge S, Lacasse Y, Forest JC, Giguere 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 Gynaecol Can. 2009 Sep;31(9):818-826. doi: 10.1016/S1701-2163(16)34300-6.
Results Reference
result
PubMed Identifier
9364597
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. doi: 10.1016/s0143-4004(97)90003-5.
Results Reference
result
PubMed Identifier
27003763
Citation
Camarena Pulido EE, Garcia Benavides L, Panduro Baron JG, Pascoe Gonzalez S, Madrigal Saray AJ, Garcia Padilla FE, Totsuka Sutto SE. Efficacy of L-arginine for preventing preeclampsia in high-risk pregnancies: A double-blind, randomized, clinical trial. Hypertens Pregnancy. 2016 May;35(2):217-25. doi: 10.3109/10641955.2015.1137586. Epub 2016 Mar 22.
Results Reference
result
PubMed Identifier
27528012
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.
Results Reference
result
PubMed Identifier
29998808
Citation
Colella M, Frerot 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.
Results Reference
result
PubMed Identifier
28090634
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. doi: 10.1113/JP273331. Epub 2017 Feb 27.
Results Reference
result
PubMed Identifier
29422215
Citation
Crispi F, Miranda J, Gratacos 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.2017.12.012.
Results Reference
result
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Arginine + Citrulline as a Supplement for Weight Gain in Fetus With a Decrease in Their Growth Curve
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