Pre-EclampsiaNCT00275158
Glomerular Injury of Preeclampsia
A study testing L-Arginine Supplementation in people with Pre-Eclampsia, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
Pre-eclampsia complicates 7 - 10% of pregnancies and constitutes a leading cause of fetal growth retardation and premature birth, as well as infant and maternal morbidity and mortality. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Pre-Eclampsia
- What is being tested?
- L-Arginine Supplementation
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2000to Dec 2003
- Phase
- Interventional
- 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 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Women selected for the study were diagnosed with pre-eclampsia in the second half of pregnancy.
- i.) an elevation of blood pressure to levels in excess of 140 systolic over 90 diastolic ii.) proteinuria determined by a urine dipstick value ≥ 2+, or quantitated at ≥ 0.5 g either per gram of creatinine or in a 24 hour urine collection.
Who cannot join
- Women with a history of underlying renal disease defined as a pre-pregnancy azotemia (serum creatinine ≥ 1.2 mg/dl) or proteinuria
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University Medical Center
Stanford, California, 94305
About this study
Official title: Effect of L-Arginine Therapy on the Glomerular Injury of Pre-Eclampsia: A Randomized Controlled Trial
Pre-eclampsia complicates 7 - 10% of pregnancies and constitutes a leading cause of fetal growth retardation and premature birth, as well as infant and maternal morbidity and mortality. The kidney is the primary site of injury resulting in high blood pressure, loss of protein into the urine and decreased kidney function. The release of vasoconstrictors over vasodilators from an abnormal placenta may underlie pre-eclampsia. Nitric Oxide (NO) is an important vasodilator that is thought to play an important role in the kidneys ability to accommodate to a healthy pregnancy. Normal pregnancy in the rat is accompanied by increased production of NO and its second messenger cGMP. There is a parallel increase in renal expression of constitutive nitric oxide synthase (NOS), the enzyme that generates NO from arginine. In the pregnant rat, an infusion of NG-nitro-L-arginine methyl ester (L-NAME), an exogenous inhibitor of NOS, has been shown to replicate some of the hemodynamic features of the syndrome of pre-eclampsia. In a recent animal study, L-arginine supplementation reversed the adverse effects of L-NAME on pregnancy by attenuating the high blood pressure and by significantly decreasing protein loss in the urine. To date, studies of the use of L-arginine supplementation to treat women with pre-eclampsia have been small or uncontrolled and have only assessed blood pressure as a primary outcome measure. We report a single center, randomized, placebo-controlled trial of L-arginine supplementation for the treatment of pre-eclampsia, in which precise physiological techniques have been utilized to assess kidney dysfunction in addition to blood pressure.
Read the detailed description
OBJECTIVE: To assess the benefit of L-arginine, the precursor to nitric oxide (NO), to blood pressure and recovery of the glomerular lesion in pre-eclampsia.
METHODS: 45 women with pre-eclampsia were randomized to receive either L-arginine or placebo until day 10 post-partum. Primary outcome measures including MAP, glomerular filtration rate and proteinuria were assessed on the third and tenth days postpartum by inulin clearance and albumin-to-creatinine (A/C) ratio. NO, cyclic guanosine 3'5' monophosphate (cGMP), endothelin-1 (ET) and asymmetric-dimethyl-arginine (ADMA) and arginine levels were assayed prior to delivery, on the third and tenth day postpartum. Healthy gravid women provided control values. Assuming a standard deviation of 10 mmHg, the study was powered to detect a 10 mmHg difference in MAP (alpha 0.05, beta 0.20) between the study groups.
RESULTS: No significant differences existed between the groups with pre-eclampsia prior to randomization. Compared to the gravid control group, women with pre-eclampsia did not reveal significantly depressed levels of serum arginine, but did reveal significantly increased serum levels of ET, cGMP and ADMA prior to delivery. Despite a significant increase in serum arginine levels due to treatment, no differences were found in the levels of NO, ET, cGMP or ADMA between the two groups with pre-eclampsia. Further, there were no significant differences in any of the primary outcome measures with both groups demonstrating equivalent improvements in both blood pressure and proteinuria.
CONCLUSION: Blood pressure and kidney function improve markedly in pre-eclampsia by the tenth day postpartum. L-arginine supplementation does not hasten this recovery.
- Conditions
- Pre-Eclampsia
- Being tested
- L-Arginine Supplementation
- Keywords
- Pre-Eclampsia, Glomerular Filtration Rate (GFR), Inulin clearance, Hypertension, L-Arginine, Nitric Oxide, cGMP, Endothelin, ADMA
- Medical subject headings
- Pre-Eclampsia, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-Arginine SupplementationDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Arterial Pressure
Glomerular Filtration Rate (inulin clearance)
Proteinuria (albumin to creatinine ratio)
Secondary outcomes (2)
Vasoactive hormone levels - Nitric Oxide, Endothelin, cGMP, ADMA
Neonatal Outcomes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2006 (estimated)
- Study startJan 2000
- Study completionDec 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pre-EclampsiaStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 45 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Center for Research Resources (NCRR)
- Investigators
- Bryan D Myers, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00275158
- Sponsor's protocol ID
- DK-52876 (completed)
- Other IDs
- DK-52876
- Status last verified
- Jan 2010
- First submitted
- 10 Jan 2006
- Last updated
- 14 Jan 2010
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of L-Arginine Therapy on the Glomerular Injury of Pre-Eclampsia: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT00275158
- Acronym / sponsor ID
- DK-52876 (completed)
- Conditions
- Pre-Eclampsia
- Keywords
- Pre-Eclampsia, Glomerular Filtration Rate (GFR), Inulin clearance, Hypertension, L-Arginine, Nitric Oxide, cGMP, Endothelin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Collaborators
- National Center for Research Resources (NCRR)
- Study start
- Jan 2000
- Study completion
- Dec 2003 (actual)
- First posted
- 11 Jan 2006 (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.
Pre-eclampsia complicates 7 - 10% of pregnancies and constitutes a leading cause of fetal growth retardation and premature birth, as well as infant and maternal morbidity and mortality. The kidney is the primary site of injury resulting in high blood pressure, loss of protein into the urine and decreased kidney function. The release of vasoconstrictors over vasodilators from an abnormal placenta may underlie pre-eclampsia. Nitric Oxide (NO) is an important vasodilator that is thought to play an important role in the kidneys ability to accommodate to a healthy pregnancy. Normal pregnancy in the rat is accompanied by increased production of NO and its second messenger cGMP. There is a parallel increase in renal expression of constitutive nitric oxide synthase (NOS), the enzyme that generates NO from arginine. In the pregnant rat, an infusion of NG-nitro-L-arginine methyl ester (L-NAME), an exogenous inhibitor of NOS, has been shown to replicate some of the hemodynamic features of the syndrome of pre-eclampsia. In a recent animal study, L-arginine supplementation reversed the adverse effects of L-NAME on pregnancy by attenuating the high blood pressure and by significantly decreasing protein loss in the urine. To date, studies of the use of L-arginine supplementation to treat women with pre-eclampsia have been small or uncontrolled and have only assessed blood pressure as a primary outcome measure. We report a single center, randomized, placebo-controlled trial of L-arginine supplementation for the treatment of pre-eclampsia, in which precise physiological techniques have been utilized to assess kidney dysfunction in addition to blood pressure.
Detailed description
OBJECTIVE: To assess the benefit of L-arginine, the precursor to nitric oxide (NO), to blood pressure and recovery of the glomerular lesion in pre-eclampsia.
METHODS: 45 women with pre-eclampsia were randomized to receive either L-arginine or placebo until day 10 post-partum. Primary outcome measures including MAP, glomerular filtration rate and proteinuria were assessed on the third and tenth days postpartum by inulin clearance and albumin-to-creatinine (A/C) ratio. NO, cyclic guanosine 3'5' monophosphate (cGMP), endothelin-1 (ET) and asymmetric-dimethyl-arginine (ADMA) and arginine levels were assayed prior to delivery, on the third and tenth day postpartum. Healthy gravid women provided control values. Assuming a standard deviation of 10 mmHg, the study was powered to detect a 10 mmHg difference in MAP (alpha 0.05, beta 0.20) between the study groups.
RESULTS: No significant differences existed between the groups with pre-eclampsia prior to randomization. Compared to the gravid control group, women with pre-eclampsia did not reveal significantly depressed levels of serum arginine, but did reveal significantly increased serum levels of ET, cGMP and ADMA prior to delivery. Despite a significant increase in serum arginine levels due to treatment, no differences were found in the levels of NO, ET, cGMP or ADMA between the two groups with pre-eclampsia. Further, there were no significant differences in any of the primary outcome measures with both groups demonstrating equivalent improvements in both blood pressure and proteinuria.
CONCLUSION: Blood pressure and kidney function improve markedly in pre-eclampsia by the tenth day postpartum. L-arginine supplementation does not hasten this recovery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Women selected for the study were diagnosed with pre-eclampsia in the second half of pregnancy.
- i.) an elevation of blood pressure to levels in excess of 140 systolic over 90 diastolic ii.) proteinuria determined by a urine dipstick value ≥ 2+, or quantitated at ≥ 0.5 g either per gram of creatinine or in a 24 hour urine collection.
Key exclusion criteria (1 listed)
- Women with a history of underlying renal disease defined as a pre-pregnancy azotemia (serum creatinine ≥ 1.2 mg/dl) or proteinuria
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 Supplementation | Drug | – |
Primary outcome
Mean Arterial Pressure
Glomerular Filtration Rate (inulin clearance)
Proteinuria (albumin to creatinine ratio)
2 secondary outcomes
Vasoactive hormone levels - Nitric Oxide, Endothelin, cGMP, ADMA
Neonatal Outcomes
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 14 Jan 2010.
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The CoPenHagen PREeClampsia and cardIOvascUlar diSease Study
Pre-Eclampsia, Atherosclerosis
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Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
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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.
Bryan D Myers, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing L-Arginine Supplementation in people with Pre-Eclampsia, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 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 2 inclusion and 1 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 14 Jan 2010. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Mean Arterial Pressure. The study lists 3 primary outcomes in all. 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 14 Jan 2010.