Fetal Growth RetardationPhase 4NCT05029778
Arginine + Citrulline as a Supplement for Weight Gain in Fetus With a Decrease in Their Growth Curve
A Phase 4 study testing L-arginine 3g + L-Citruline 2 g in people with Fetal Growth Retardation, run by Hospital Civil de Guadalajara.
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… Read more about this study
- Who is it for?
- Ages 18 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Fetal Growth Retardation
- What is being tested?
- L-arginine 3g + L-Citruline 2 g
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 41 participants
- Where
- No sites listed yet
- Study dates
- 20 Oct 2021to 20 Jan 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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 .
Who cannot join
- 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
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- 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
Trial locations and contacts
No sites are listed yet.
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Fetal Growth Retardation
- Being tested
- L-arginine 3g + L-Citruline 2 g, Placebo
- Keywords
- L-arginine, l-Citruline, Fetal growth, percentile,
- Medical subject headings
- Fetal Growth Retardation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-arginine 3g + L-Citruline 2 gDietary supplement
Also called L-arginine 3g, L-Citruline 2 g
receive L-arginine 3g + l-Citruline 2 g PO, for 24 h, until birth.
PlaceboDrug
receive placebo 3g PO, for 24 h, until birth.
| Study group | Role | What they receive |
|---|---|---|
| Experimental L-arginine 3 g and L-citruline 2 g | Experimental | Drug: L-arginine 3g and L-citruline 2g, Food supplement, PO , for 24 h, until birth Receives: Dietary Supplement: L-arginine 3g + L-Citruline 2 g |
| placebo | Experimental | Placebo 3g ( starch ) PO for 24 h. until birth Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fetal Growth
fetal weight gain
Measured: 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2021
- Study start20 Oct 2021 (estimated)
- Primary completion20 Oct 2021 (estimated)
- Study completion20 Jan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Fetal Growth RetardationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Clinical Trial open controlled parallel randomized simple
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 41 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Civil de Guadalajara
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jorge Bravo Rubio, Hospital Civil de Guadalajara
- Investigators
- Milton Omar Guzman Ornelas, Dr., Study director, University of Guadalajara
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05029778
- Sponsor's protocol ID
- 097/20
- Status last verified
- Aug 2021
- First submitted
- 25 Aug 2021
- Last updated
- 1 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 19768178Ananth 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.
PubMed 19786331Barker 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.
PubMed 19562567Bourdon 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.
PubMed 26865647Bujold 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.
PubMed 19941706Byrne 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.
PubMed 9364597Camarena 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.
PubMed 27003763Chen 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.
PubMed 27528012Colella 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.
PubMed 29998808Cottrell 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.
PubMed 28090634Crispi 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.
PubMed 29422215
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05029778
- Acronym / sponsor ID
- 097/20
- Conditions
- Fetal Growth Retardation
- Keywords
- L-arginine, l-Citruline, Fetal growth, percentile,
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 41 participants (estimated)
- Lead sponsor
- Hospital Civil de GuadalajaraUniversity, hospital or other
- Study start
- 20 Oct 2021 (estimated)
- Primary completion
- 20 Oct 2021 (estimated)
- Study completion
- 20 Jan 2024 (estimated)
- First posted
- 1 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Clinical Trial open controlled parallel randomized simple
| Arm | Type | Receives |
|---|---|---|
| Experimental L-arginine 3 g and L-citruline 2 g | Experimental | Dietary Supplement: L-arginine 3g + L-Citruline 2 gDrug: L-arginine 3g and L-citruline 2g, Food supplement, PO , for 24 h, until birth |
| placebo | Experimental | Drug: PlaceboPlacebo 3g ( starch ) PO for 24 h. until birth |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-arginine 3g + L-Citruline 2 gAlso: L-arginine 3g, L-Citruline 2 greceive L-arginine 3g + l-Citruline 2 g PO, for 24 h, until birth. | Dietary supplement | Experimental L-arginine 3 g and L-citruline 2 g |
| Placeboreceive placebo 3g PO, for 24 h, until birth. | Drug | placebo |
Primary outcome
Fetal Growth
Time frame: 10 weeks
fetal weight gain
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2021.
- Background: PubMed 19768178Dover 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 publication: PubMed 19786331Ananth 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 publication: PubMed 19562567Barker 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 publication: PubMed 26865647Bourdon 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 publication: PubMed 19941706Bujold 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 publication: PubMed 9364597Byrne 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 publication: PubMed 27003763Camarena 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 publication: PubMed 27528012Chen 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 publication: PubMed 29998808Colella 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 publication: PubMed 28090634Cottrell 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 publication: PubMed 29422215Crispi 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Milton Omar Guzman Ornelas, Dr. study director
University of Guadalajara
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing L-arginine 3g + L-Citruline 2 g in people with Fetal Growth Retardation, run by Hospital Civil de Guadalajara.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jorge Bravo Rubio, Dr (3221186759, naranjo125@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fetal Growth (time frame: 10 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05029778, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2021.