Blood PressurePhase 1NCT00743210
Oral L-Citrulline and ADMA in Pregnancy
A Phase 1 study testing L-citrulline in people with Blood Pressure, run by University of Pittsburgh at 1 site in United States.
Trial summary
The purpose of this study is to determine if oral of L-citrulline (3 grams/day) for 3 weeks provided in mid-pregnancy to obese subjects will decrease the plasma ADMA/L-arginine ratio, lower maternal blood pressure, improve endothelial-dependent vascular function and peripheral vascular stiffness, and improve uterine… Read more about this study
- Who is it for?
- Ages 14 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Blood Pressure
- What is being tested?
- L-citrulline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2010to Jun 2013
- Phase
- Phase 1
- 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 14 to 40 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Pre-pregnancy body mass index greater than or equal to 30kg/m2
- Primiparity
- Singleton pregnancy
- Gestational age at randomization between 10 and 14 weeks based on clinical information and evaluation of earliest ultrasound
- Maternal age between 14 and 40 years
Who cannot join
- chronic hypertension
- pregestational diabetes on medication (insulin, glyburide)
- major fetal anomaly or demise
- planned termination of the pregnancy
- collagen vascular disease (autoimmune disease) on medication
- renal disease
Show all 12Show fewer
- epilepsy or other seizure disorder
- active or chronic liver disease
- heart disease
- cigarette smoker
- known illicit drug or alcohol abuse during current pregnancy
- already taking L-citrulline as a supplement (1gram/day or more)
Trial locations and contacts
1 site in 1 country.
United States1 site
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Phase 1 Study of Oral L-citrulline on ADMA/L-arginine and Endothelial-dependent Vascular Function in Pregnancy.
The purpose of this study is to determine if oral of L-citrulline (3 grams/day) for 3 weeks provided in mid-pregnancy to obese subjects will decrease the plasma ADMA/L-arginine ratio, lower maternal blood pressure, improve endothelial-dependent vascular function and peripheral vascular stiffness, and improve uterine artery Doppler resistance and flow.
Read the detailed description
The pregnancy-specific syndrome preeclampsia is a leading cause of maternal and fetal morbidity and mortality. The underlying cause of preeclampsia is unknown, however several pre-existing maternal conditions are associated with an increased risk of preeclampsia including: diabetes, hypertension, renal dysfunction, and obesity. Among these conditions, obesity has been increasing in the population, such that 30% of the adult population in the US is now considered obese, and because of this obesity has the largest attributable risk for preeclampsia, accounting for 15 to 32% of the population attributable risk for preeclampsia. There is abundant evidence that pre-pregnancy obesity increases the risk of preeclampsia. However, it is unknown how pre-pregnancy obesity increases the risk of preeclampsia, how obesity-mediated metabolic aberrations interact with current hypotheses of the pathogenesis of preeclampsia, and why only a subset of obese women (~6-8%) develops preeclampsia. Several lines of evidence indicate that endothelial dysfunction is a central feature of the pathophysiology of preeclampsia, and endothelial dysfunction is a common endpoint of obesity. Asymmetric dimethylarginine (ADMA) is a methylated metabolite of the amino acid L-arginine and an endogenous inhibitor of nitric oxide synthase (NOS). High concentrations of ADMA contribute to endothelial dysfunction and ADMA inhibits angiogenesis and arteriogenesis, activities important in pregnancy and deficient in preeclampsia. ADMA is higher in obesity and ADMA concentrations are higher early in pregnancy among women who later develop preeclampsia. This protocol describes a randomized placebo-controlled trial of L-citrulline vs. placebo in 80 obese pregnant women from twelve to twenty weeks gestation, to determine whether L-citrulline supplementation decreases the plasma ADMA/L-arginine ratio, lowers maternal blood pressure, improves endothelial-dependent vascular function and peripheral vascular stiffness, and improvement in uterine artery Doppler resistance and flow. We will compare the data obtained from these obese pregnant women to the same measures obtained from 40 untreated lean pregnant women.
- Conditions
- Blood Pressure
- Being tested
- L-citrulline, Placebo
- Keywords
- pregnancy, obesity, asymmetric dimethylarginine, L-arginine, L-citrulline
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-citrullineDrug
Oral L-citrulline, 3 grams once per day for 3 weeks.
PlaceboDrug
Placebo, 3 grams once per day for 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Oral L-citrulline, 3 grams once per day for 3 weeks. Receives: Drug: L-citrulline |
| 2 | Placebo comparator | Placebo, 3 grams once per day for 3 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate blood pressure changes in response to oral L-citrulline or placebo treatment in uncomplicated obese pregnant women during the second trimester of pregnancy.
Measured: 3 weeks
Secondary outcomes (1)
To evaluate the changes in plasma ADMA/L-arginine ratio, endothelial-dependent vascular function and peripheral vascular stiffness, and uterine artery Doppler resistance and flow.
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2008 (estimated)
- Study startJan 2010
- Primary completionJun 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Blood PressureStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Robert Powers, University of Pittsburgh
- Investigators
- Carl A Hubel, PhD, Principal investigator, Department of Obstetrics & Gynecology and Reproductive Sciences, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00743210
- Sponsor's protocol ID
- 2P01HD030367-ARG
- Other IDs
- P01HD030367-09
- Status last verified
- Jul 2014
- First submitted
- 26 Aug 2008
- Last updated
- 16 Jul 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Oral L-citrulline on ADMA/L-arginine and Endothelial-dependent Vascular Function in Pregnancy.
- ClinicalTrials.gov ID
- NCT00743210
- Acronym / sponsor ID
- 2P01HD030367-ARG
- Conditions
- Blood Pressure
- Keywords
- pregnancy, obesity, asymmetric dimethylarginine, L-arginine, L-citrulline
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Jan 2010
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 28 Aug 2008 (estimated)
- 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.
The purpose of this study is to determine if oral of L-citrulline (3 grams/day) for 3 weeks provided in mid-pregnancy to obese subjects will decrease the plasma ADMA/L-arginine ratio, lower maternal blood pressure, improve endothelial-dependent vascular function and peripheral vascular stiffness, and improve uterine artery Doppler resistance and flow.
Detailed description
The pregnancy-specific syndrome preeclampsia is a leading cause of maternal and fetal morbidity and mortality. The underlying cause of preeclampsia is unknown, however several pre-existing maternal conditions are associated with an increased risk of preeclampsia including: diabetes, hypertension, renal dysfunction, and obesity. Among these conditions, obesity has been increasing in the population, such that 30% of the adult population in the US is now considered obese, and because of this obesity has the largest attributable risk for preeclampsia, accounting for 15 to 32% of the population attributable risk for preeclampsia. There is abundant evidence that pre-pregnancy obesity increases the risk of preeclampsia. However, it is unknown how pre-pregnancy obesity increases the risk of preeclampsia, how obesity-mediated metabolic aberrations interact with current hypotheses of the pathogenesis of preeclampsia, and why only a subset of obese women (~6-8%) develops preeclampsia. Several lines of evidence indicate that endothelial dysfunction is a central feature of the pathophysiology of preeclampsia, and endothelial dysfunction is a common endpoint of obesity. Asymmetric dimethylarginine (ADMA) is a methylated metabolite of the amino acid L-arginine and an endogenous inhibitor of nitric oxide synthase (NOS). High concentrations of ADMA contribute to endothelial dysfunction and ADMA inhibits angiogenesis and arteriogenesis, activities important in pregnancy and deficient in preeclampsia. ADMA is higher in obesity and ADMA concentrations are higher early in pregnancy among women who later develop preeclampsia. This protocol describes a randomized placebo-controlled trial of L-citrulline vs. placebo in 80 obese pregnant women from twelve to twenty weeks gestation, to determine whether L-citrulline supplementation decreases the plasma ADMA/L-arginine ratio, lowers maternal blood pressure, improves endothelial-dependent vascular function and peripheral vascular stiffness, and improvement in uterine artery Doppler resistance and flow. We will compare the data obtained from these obese pregnant women to the same measures obtained from 40 untreated lean pregnant women.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: L-citrullineOral L-citrulline, 3 grams once per day for 3 weeks. |
| 2 | Placebo comparator | Drug: PlaceboPlacebo, 3 grams once per day for 3 weeks. |
Who may qualify
- Ages
- 14 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Pre-pregnancy body mass index greater than or equal to 30kg/m2
- Primiparity
- Singleton pregnancy
- Gestational age at randomization between 10 and 14 weeks based on clinical information and evaluation of earliest ultrasound
- Maternal age between 14 and 40 years
Key exclusion criteria (12 listed)
- chronic hypertension
- pregestational diabetes on medication (insulin, glyburide)
- major fetal anomaly or demise
- planned termination of the pregnancy
- collagen vascular disease (autoimmune disease) on medication
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-citrullineOral L-citrulline, 3 grams once per day for 3 weeks. | Drug | 1 |
| PlaceboPlacebo, 3 grams once per day for 3 weeks. | Drug | 2 |
Primary outcome
To evaluate blood pressure changes in response to oral L-citrulline or placebo treatment in uncomplicated obese pregnant women during the second trimester of pregnancy.
Time frame: 3 weeks
1 secondary outcome
To evaluate the changes in plasma ADMA/L-arginine ratio, endothelial-dependent vascular function and peripheral vascular stiffness, and uterine artery Doppler resistance and flow.
Time frame: 3 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2014.
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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.
Carl A Hubel, PhD principal investigator
Department of Obstetrics & Gynecology and Reproductive Sciences, University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing L-citrulline in people with Blood Pressure, run by University of Pittsburgh at 1 site in United States.
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 5 inclusion and 12 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: finished, as of the sponsor's last update on 16 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate blood pressure changes in response to oral L-citrulline or placebo treatment in uncomplicated obese pregnant women during the second trimester of pregnancy. (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Jul 2014.