Heart Septal Defects, VentricularPhase 1L-carnNCT01825369
Aberrations in Carnitine Homeostasis in Congenital Heart Disease With Increased Pulmonary Blood Flow
A Phase 1 study testing IV L-carnitine in people with Heart Septal Defects, Ventricular and Atrioventricular Septal Defect, run by University of California, San Francisco at 1 site in United States.
Trial summary
Infants with congenital heart disease and increased pulmonary blood flow have altered carnitine homeostasis that is associated with clinical outcomes; and L-carnitine treatment will attenuate these alterations and improve clinical outcomes. Read more about this study
- Who is it for?
- Ages 2 to 12 months
- Conditions the study is for
- Heart Septal Defects, Ventricular, Atrioventricular Septal Defect
- What is being tested?
- IV L-carnitine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2014to Jul 2020
- 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 2 to 12 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- have unrestrictive VSD, AVSD
- are undergoing complete repair
- are between 2-12 months of age
- are corrected gestational age ≥34 weeks
- will have an indwelling arterial or venous line
- have not had enteral or parenteral nutrition for at least 6 hrs
Who cannot join
- have body weight < 2.0 kg
- pulmonary artery or vein abnormalities not being addressed surgically
- suspected or proven in-born error of metabolism
- have other major congenital abnormalities that affect the cardiopulmonary system
- are taking carnitine supplementation
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California San Francisco
San Francisco, California, 94143-0106
About this study
Official title: Phase 1 Study of the Safety and Pharmacokinetics of Perioperative IV L-carnitine Administration in Patients With Congenital Heart Disease With Increased Pulmonary Blood Flow
Infants with congenital heart disease and increased pulmonary blood flow have altered carnitine homeostasis that is associated with clinical outcomes; and L-carnitine treatment will attenuate these alterations and improve clinical outcomes.
The investigators will pilot a trial assessing the safety and pharmacokinetics of perioperative IV L-carnitine administration in these patients. To this end, a pilot clinical trial is proposed. Infants with ventricular septal defects or atrioventricular septal defects undergoing complete surgical repair will receive L-carnitine (25, 50, or 100 mg/kg, IV) just prior to cardiopulmonary bypass (CPB) and 2hr after CPB. Carnitine levels will be measured before CPB, and before and 0.5, 1.5, 3, 5, 9, 12, and 24h after the second dose. The safety, pharmacokinetic profile, feasibility, and effect of L-carnitine administration on biochemical parameters, as well as clinical outcomes will be determined. The investigators expect this pilot to provide the data needed to proceed with a placebo-based randomized, controlled, trial.
Read the detailed description
AIM: To pilot a trial assessing the safety and pharmacokinetics (PK) of perioperative IV L-carnitine administration in these patients. To this end, a pilot clinical trial is proposed. Infants with VSD or AVSD undergoing complete repair will receive L-carnitine, in one of 3 doses (25, 50, or 100 mg/kg, IV), just prior to CPB, and again 2 hr after CPB. Serial blood samples will be obtained to determine free, total, and acylcarnitine levels, and plasma markers of mitochondrial function, oxidative stress, and bioavailable NO. Adverse events will be sought, and clinical outcomes will be assessed.
Study design: The inclusion and exclusion criteria are as described in Aim 3A except only infants with VSD or AVSD will be enrolled (no TOF). The safety profile of L-carnitine is outstanding, with no reports of toxicity from overdose reported113. In fact, the only adverse reactions reported are transient nausea and vomiting, and less commonly gastritis. However, although rare, seizures have been reported to occur in patients receiving L-carnitine. Therefore, the major adverse events that will be monitored include evidence of seizure activity and GI bleeding. As per routine, any patient suspected of having seizures is monitored with continuous EEG. Dosing is not well studied in children, particularly critically ill children67, 114-116117. In addition, the effect of CPB on L-carnitine clearance in children is not known. Therefore, a major goal of this sub-aim is to establish a pharmacokinetic profile of L-carnitine in this patient population undergoing surgery with CPB, in order to move forward with a larger randomized trial powered for efficacy in prevention of increased PVR post-bypass in at-risk infants. Plasma concentration profiles after IV bolus dosing in adults were described by a two-compartmental model67, 113, 114, 118. Usual pediatric dosing is not well delineated, but recommendations include a 50 mg/kg bolus followed by an infusion of 50mg/kg/day, that can be increased to 300 mg/kg/day113, 119. Therefore, we will begin at a lower dose (25 mg/kg), and escalate the dose after each group of 5. No intra-patient escalation will be allowed and the dose will not be escalated until all patients in the current dose level have been followed to hospital discharge or 30 days post-op and the safety and PK data have been analyzed. The DSMB will approve all dose escalations. The dosing goal will be to achieve normal or supra-normal free carnitine levels (~50 μmol/L) and low AC levels (~3 μmol/L) just before and for 24 hrs after CPB; the period with the greatest risk of pulmonary vascular morbidity.
- Being tested
- IV L-carnitine
- Keywords
- congenital heart disease, ventricular septal defect, atrioventricular septal defect, increased pulmonary blood flow, nitric oxide
- Medical subject headings
- Heart Septal Defects, Ventricular, Atrioventricular Septal Defect, Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IV L-carnitineDrug
See arm description
| Study group | Role | What they receive |
|---|---|---|
| IV L-carnitine | Experimental | L-carnitine (25, 50, or 100mg/kg IV) will be given, 30-60 minutes prior to the initiation of CPB, and a second dose ~2 hr. following separation from CPB (with a minimum of 4 hrs from initial dose). The first 5 subjects will receive 25 mg/kg, with an escalation of dose after each 5 subjects enrolled. The study drug will be brought to the operating room and administered over 5 minutes by the anesthesiologist after an IV has been placed. Prior to the administration of the study drug, and again 24 and 48 hrs after CPB, 3.0 ml of blood will be collected for determinations of carnitine levels (free, total, and acylcarnitine), mitochondrial function, ROS and bioavailable NO as described in Aim 3A. Additional blood (0.5-1.0 ml) will be obtained to determine carnitine levels before CPB, and then before and 0.5, 1.5, 3, 5, 9, 12, and 24h after the second dose. Receives: Drug: IV L-carnitine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood carnitine level (free, total, and acylcarnitine)
Measured: At enrollment (first dose), and again 24 and 48 hrs after enrollment. 2 hours after enrollment (at time of second dose) and 0.5, 1.5, 3, 5, 9, 12, and 24h after the second dose.
Secondary outcomes (13)
Bioavailable nitric oxide
Measured: At enrollment (first dose), and again 24 and 48 hrs after enrollment.
Plasma levels of superoxide
Measured: At enrollment (first dose), and again 24 and 48 hrs after enrollment.
Carnitine Palmityl Transporter-1 and -2 expression
Measured: At enrollment (first dose), and again 24 and 48 hrs after enrollment.
Cardiopulmonary bypass
Measured: Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
Echocardiographic measurements
Estimates of PPA and right ventricular (RV) function by transesophageal ECHO (TEE)
Measured: Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
Blood BNP level
Measured: Daily during the hospitalization, estimated to be an average of 2 weeks
Duration of mechanical ventilation
Measured: During hospitalization which is an average of 2 weeks
Vasopressor infusions
Measured: Duration of hospitalization which is an average of 2 weeks
Need for inhaled nitric oxide
Measured: During hospitalization (average of 2 weeks)
Incidence of low cardiac output syndrome
Measured: Postoperative hospitalization (average of 2 weeks)
Need for extracorporeal life support
Measured: During hospitalization (average of 2 weeks)
Plasma H202 levels
Measured: At enrollment (first dose), and again 24 and 48 hrs after enrollment.
Aortic cross clamp times
Measured: Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2013 (estimated)
- Study startDec 2014
- Primary completionJul 2020 (estimated)
- Study completionJul 2020 (estimated)
Why it stopped: Changes to cardiac surgery program
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Heart Septal Defects, VentricularStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeffrey Fineman, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01825369
- Sponsor's protocol ID
- FinemanCarnitine
- Acronym
- L-carn
- Status last verified
- May 2020
- First submitted
- 28 Mar 2013
- Last updated
- 6 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ghorishi Z, Milstein JM, Poulain FR, Moon-Grady A, Tacy T, Bennett SH, Fineman JR, Eldridge MW. Shear stress paradigm for perinatal fractal arterial network remodeling in lambs with pulmonary hypertension and increased pulmonary blood flow. Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H3006-18. doi: 10.1152/ajpheart.01012.2006. Epub 2007 Feb 16.
PubMed 17308003Black SM, Kumar S, Wiseman D, Ravi K, Wedgwood S, Ryzhov V, Fineman JR. Pediatric pulmonary hypertension: Roles of endothelin-1 and nitric oxide. Clin Hemorheol Microcirc. 2007;37(1-2):111-20.
PubMed 17641401Sharma S, Grobe AC, Wiseman DA, Kumar S, Englaish M, Najwer I, Benavidez E, Oishi P, Azakie A, Fineman JR, Black SM. Lung antioxidant enzymes are regulated by development and increased pulmonary blood flow. Am J Physiol Lung Cell Mol Physiol. 2007 Oct;293(4):L960-71. doi: 10.1152/ajplung.00449.2006. Epub 2007 Jul 13.
PubMed 17631609Lakshminrusimha S, Wiseman D, Black SM, Russell JA, Gugino SF, Oishi P, Steinhorn RH, Fineman JR. The role of nitric oxide synthase-derived reactive oxygen species in the altered relaxation of pulmonary arteries from lambs with increased pulmonary blood flow. Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1491-7. doi: 10.1152/ajpheart.00185.2007. Epub 2007 May 18.
PubMed 17513498Oishi P, Sharma S, Grobe A, Azakie A, Harmon C, Johengen MJ, Hsu JH, Fratz S, Black SM, Fineman JR. Alterations in cGMP, soluble guanylate cyclase, phosphodiesterase 5, and B-type natriuretic peptide induced by chronic increased pulmonary blood flow in lambs. Pediatr Pulmonol. 2007 Nov;42(11):1057-71. doi: 10.1002/ppul.20696.
PubMed 17902145Sud N, Sharma S, Wiseman DA, Harmon C, Kumar S, Venema RC, Fineman JR, Black SM. Nitric oxide and superoxide generation from endothelial NOS: modulation by HSP90. Am J Physiol Lung Cell Mol Physiol. 2007 Dec;293(6):L1444-53. doi: 10.1152/ajplung.00175.2007. Epub 2007 Sep 7.
PubMed 17827253Oishi PE, Wiseman DA, Sharma S, Kumar S, Hou Y, Datar SA, Azakie A, Johengen MJ, Harmon C, Fratz S, Fineman JR, Black SM. Progressive dysfunction of nitric oxide synthase in a lamb model of chronically increased pulmonary blood flow: a role for oxidative stress. Am J Physiol Lung Cell Mol Physiol. 2008 Nov;295(5):L756-66. doi: 10.1152/ajplung.00146.2007. Epub 2008 Aug 29.
PubMed 18757524Sharma S, Sud N, Wiseman DA, Carter AL, Kumar S, Hou Y, Rau T, Wilham J, Harmon C, Oishi P, Fineman JR, Black SM. Altered carnitine homeostasis is associated with decreased mitochondrial function and altered nitric oxide signaling in lambs with pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2008 Jan;294(1):L46-56. doi: 10.1152/ajplung.00247.2007. Epub 2007 Nov 16.
PubMed 18024721Kumar S, Sun X, Sharma S, Aggarwal S, Ravi K, Fineman JR, Black SM. GTP cyclohydrolase I expression is regulated by nitric oxide: role of cyclic AMP. Am J Physiol Lung Cell Mol Physiol. 2009 Aug;297(2):L309-17. doi: 10.1152/ajplung.90538.2008. Epub 2009 May 15.
PubMed 19447893Sharma S, Kumar S, Sud N, Wiseman DA, Tian J, Rehmani I, Datar S, Oishi P, Fratz S, Venema RC, Fineman JR, Black SM. Alterations in lung arginine metabolism in lambs with pulmonary hypertension associated with increased pulmonary blood flow. Vascul Pharmacol. 2009 Nov-Dec;51(5-6):359-64. doi: 10.1016/j.vph.2009.09.005. Epub 2009 Oct 8.
PubMed 19818875Tian J, Smith A, Nechtman J, Podolsky R, Aggarwal S, Snead C, Kumar S, Elgaish M, Oishi P, Goerlach A, Fratz S, Hess J, Catravas JD, Verin AD, Fineman JR, She JX, Black SM. Effect of PPARgamma inhibition on pulmonary endothelial cell gene expression: gene profiling in pulmonary hypertension. Physiol Genomics. 2009 Dec 30;40(1):48-60. doi: 10.1152/physiolgenomics.00094.2009. Epub 2009 Oct 13.
PubMed 19825830Aggarwal S, Gross C, Fineman JR, Black SM. Oxidative stress and the development of endothelial dysfunction in congenital heart disease with increased pulmonary blood flow: lessons from the neonatal lamb. Trends Cardiovasc Med. 2010 Oct;20(7):238-46. doi: 10.1016/j.tcm.2011.11.010.
PubMed 22293025Sharma S, Kumar S, Wiseman DA, Kallarackal S, Ponnala S, Elgaish M, Tian J, Fineman JR, Black SM. Perinatal changes in superoxide generation in the ovine lung: Alterations associated with increased pulmonary blood flow. Vascul Pharmacol. 2010 Jul-Aug;53(1-2):38-52. doi: 10.1016/j.vph.2010.03.005. Epub 2010 Mar 31.
PubMed 20362073Aggarwal S, Gross CM, Kumar S, Datar S, Oishi P, Kalkan G, Schreiber C, Fratz S, Fineman JR, Black SM. Attenuated vasodilatation in lambs with endogenous and exogenous activation of cGMP signaling: role of protein kinase G nitration. J Cell Physiol. 2011 Dec;226(12):3104-13. doi: 10.1002/jcp.22692.
PubMed 21351102Sharma S, Sun X, Kumar S, Rafikov R, Aramburo A, Kalkan G, Tian J, Rehmani I, Kallarackal S, Fineman JR, Black SM. Preserving mitochondrial function prevents the proteasomal degradation of GTP cyclohydrolase I. Free Radic Biol Med. 2012 Jul 15;53(2):216-29. doi: 10.1016/j.freeradbiomed.2012.03.016. Epub 2012 Apr 16.
PubMed 22583703
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of the Safety and Pharmacokinetics of Perioperative IV L-carnitine Administration in Patients With Congenital Heart Disease With Increased Pulmonary Blood Flow
- ClinicalTrials.gov ID
- NCT01825369
- Acronym / sponsor ID
- L-carn / FinemanCarnitine
- Keywords
- congenital heart disease, ventricular septal defect, atrioventricular septal defect, increased pulmonary blood flow, nitric oxide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Changes to cardiac surgery program
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- Dec 2014 (actual)
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Jul 2020 (estimated)
- First posted
- 5 Apr 2013 (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.
Infants with congenital heart disease and increased pulmonary blood flow have altered carnitine homeostasis that is associated with clinical outcomes; and L-carnitine treatment will attenuate these alterations and improve clinical outcomes.
The investigators will pilot a trial assessing the safety and pharmacokinetics of perioperative IV L-carnitine administration in these patients. To this end, a pilot clinical trial is proposed. Infants with ventricular septal defects or atrioventricular septal defects undergoing complete surgical repair will receive L-carnitine (25, 50, or 100 mg/kg, IV) just prior to cardiopulmonary bypass (CPB) and 2hr after CPB. Carnitine levels will be measured before CPB, and before and 0.5, 1.5, 3, 5, 9, 12, and 24h after the second dose. The safety, pharmacokinetic profile, feasibility, and effect of L-carnitine administration on biochemical parameters, as well as clinical outcomes will be determined. The investigators expect this pilot to provide the data needed to proceed with a placebo-based randomized, controlled, trial.
Detailed description
AIM: To pilot a trial assessing the safety and pharmacokinetics (PK) of perioperative IV L-carnitine administration in these patients. To this end, a pilot clinical trial is proposed. Infants with VSD or AVSD undergoing complete repair will receive L-carnitine, in one of 3 doses (25, 50, or 100 mg/kg, IV), just prior to CPB, and again 2 hr after CPB. Serial blood samples will be obtained to determine free, total, and acylcarnitine levels, and plasma markers of mitochondrial function, oxidative stress, and bioavailable NO. Adverse events will be sought, and clinical outcomes will be assessed.
Study design: The inclusion and exclusion criteria are as described in Aim 3A except only infants with VSD or AVSD will be enrolled (no TOF). The safety profile of L-carnitine is outstanding, with no reports of toxicity from overdose reported113. In fact, the only adverse reactions reported are transient nausea and vomiting, and less commonly gastritis. However, although rare, seizures have been reported to occur in patients receiving L-carnitine. Therefore, the major adverse events that will be monitored include evidence of seizure activity and GI bleeding. As per routine, any patient suspected of having seizures is monitored with continuous EEG. Dosing is not well studied in children, particularly critically ill children67, 114-116117. In addition, the effect of CPB on L-carnitine clearance in children is not known. Therefore, a major goal of this sub-aim is to establish a pharmacokinetic profile of L-carnitine in this patient population undergoing surgery with CPB, in order to move forward with a larger randomized trial powered for efficacy in prevention of increased PVR post-bypass in at-risk infants. Plasma concentration profiles after IV bolus dosing in adults were described by a two-compartmental model67, 113, 114, 118. Usual pediatric dosing is not well delineated, but recommendations include a 50 mg/kg bolus followed by an infusion of 50mg/kg/day, that can be increased to 300 mg/kg/day113, 119. Therefore, we will begin at a lower dose (25 mg/kg), and escalate the dose after each group of 5. No intra-patient escalation will be allowed and the dose will not be escalated until all patients in the current dose level have been followed to hospital discharge or 30 days post-op and the safety and PK data have been analyzed. The DSMB will approve all dose escalations. The dosing goal will be to achieve normal or supra-normal free carnitine levels (~50 μmol/L) and low AC levels (~3 μmol/L) just before and for 24 hrs after CPB; the period with the greatest risk of pulmonary vascular morbidity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IV L-carnitine | Experimental | Drug: IV L-carnitineL-carnitine (25, 50, or 100mg/kg IV) will be given, 30-60 minutes prior to the initiation of CPB, and a second dose ~2 hr. following separation from CPB (with a minimum of 4 hrs from initial dose). The first 5 subjects will receive 25 mg/kg, with an escalation of dose after each 5 subjects enrolled. The study drug will be brought to the operating room and administered over 5 minutes by the anesthesiologist after an IV has been placed. Prior to the administration of the study drug, and again 24 and 48 hrs after CPB, 3.0 ml of blood will be collected for determinations of carnitine levels (free, total, and acylcarnitine), mitochondrial function, ROS and bioavailable NO as described in Aim 3A. Additional blood (0.5-1.0 ml) will be obtained to determine carnitine levels before CPB, and then before and 0.5, 1.5, 3, 5, 9, 12, and 24h after the second dose. |
Who may qualify
- Ages
- 2 to 12 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- have unrestrictive VSD, AVSD
- are undergoing complete repair
- are between 2-12 months of age
- are corrected gestational age ≥34 weeks
- will have an indwelling arterial or venous line
Key exclusion criteria (5 listed)
- have body weight < 2.0 kg
- pulmonary artery or vein abnormalities not being addressed surgically
- suspected or proven in-born error of metabolism
- have other major congenital abnormalities that affect the cardiopulmonary system
- are taking carnitine supplementation
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 |
|---|---|---|
| IV L-carnitineSee arm description | Drug | IV L-carnitine |
Primary outcome
Blood carnitine level (free, total, and acylcarnitine)
Time frame: At enrollment (first dose), and again 24 and 48 hrs after enrollment. 2 hours after enrollment (at time of second dose) and 0.5, 1.5, 3, 5, 9, 12, and 24h after the second dose.
13 secondary outcomes
Bioavailable nitric oxide
Time frame: At enrollment (first dose), and again 24 and 48 hrs after enrollment.
Plasma levels of superoxide
Time frame: At enrollment (first dose), and again 24 and 48 hrs after enrollment.
Carnitine Palmityl Transporter-1 and -2 expression
Time frame: At enrollment (first dose), and again 24 and 48 hrs after enrollment.
Cardiopulmonary bypass
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
Echocardiographic measurements
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
Blood BNP level
Time frame: Daily during the hospitalization, estimated to be an average of 2 weeks
Duration of mechanical ventilation
Time frame: During hospitalization which is an average of 2 weeks
Vasopressor infusions
Time frame: Duration of hospitalization which is an average of 2 weeks
Need for inhaled nitric oxide
Time frame: During hospitalization (average of 2 weeks)
Incidence of low cardiac output syndrome
Time frame: Postoperative hospitalization (average of 2 weeks)
Need for extracorporeal life support
Time frame: During hospitalization (average of 2 weeks)
Plasma H202 levels
Time frame: At enrollment (first dose), and again 24 and 48 hrs after enrollment.
Aortic cross clamp times
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2020.
- Background: PubMed 17308003Ghorishi Z, Milstein JM, Poulain FR, Moon-Grady A, Tacy T, Bennett SH, Fineman JR, Eldridge MW. Shear stress paradigm for perinatal fractal arterial network remodeling in lambs with pulmonary hypertension and increased pulmonary blood flow. Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H3006-18. doi: 10.1152/ajpheart.01012.2006. Epub 2007 Feb 16.
- Background: PubMed 17641401Black SM, Kumar S, Wiseman D, Ravi K, Wedgwood S, Ryzhov V, Fineman JR. Pediatric pulmonary hypertension: Roles of endothelin-1 and nitric oxide. Clin Hemorheol Microcirc. 2007;37(1-2):111-20.
- Background: PubMed 17631609Sharma S, Grobe AC, Wiseman DA, Kumar S, Englaish M, Najwer I, Benavidez E, Oishi P, Azakie A, Fineman JR, Black SM. Lung antioxidant enzymes are regulated by development and increased pulmonary blood flow. Am J Physiol Lung Cell Mol Physiol. 2007 Oct;293(4):L960-71. doi: 10.1152/ajplung.00449.2006. Epub 2007 Jul 13.
- Background: PubMed 17513498Lakshminrusimha S, Wiseman D, Black SM, Russell JA, Gugino SF, Oishi P, Steinhorn RH, Fineman JR. The role of nitric oxide synthase-derived reactive oxygen species in the altered relaxation of pulmonary arteries from lambs with increased pulmonary blood flow. Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1491-7. doi: 10.1152/ajpheart.00185.2007. Epub 2007 May 18.
- Background: PubMed 17902145Oishi P, Sharma S, Grobe A, Azakie A, Harmon C, Johengen MJ, Hsu JH, Fratz S, Black SM, Fineman JR. Alterations in cGMP, soluble guanylate cyclase, phosphodiesterase 5, and B-type natriuretic peptide induced by chronic increased pulmonary blood flow in lambs. Pediatr Pulmonol. 2007 Nov;42(11):1057-71. doi: 10.1002/ppul.20696.
- Background: PubMed 17827253Sud N, Sharma S, Wiseman DA, Harmon C, Kumar S, Venema RC, Fineman JR, Black SM. Nitric oxide and superoxide generation from endothelial NOS: modulation by HSP90. Am J Physiol Lung Cell Mol Physiol. 2007 Dec;293(6):L1444-53. doi: 10.1152/ajplung.00175.2007. Epub 2007 Sep 7.
- Background: PubMed 18757524Oishi PE, Wiseman DA, Sharma S, Kumar S, Hou Y, Datar SA, Azakie A, Johengen MJ, Harmon C, Fratz S, Fineman JR, Black SM. Progressive dysfunction of nitric oxide synthase in a lamb model of chronically increased pulmonary blood flow: a role for oxidative stress. Am J Physiol Lung Cell Mol Physiol. 2008 Nov;295(5):L756-66. doi: 10.1152/ajplung.00146.2007. Epub 2008 Aug 29.
- Background: PubMed 18024721Sharma S, Sud N, Wiseman DA, Carter AL, Kumar S, Hou Y, Rau T, Wilham J, Harmon C, Oishi P, Fineman JR, Black SM. Altered carnitine homeostasis is associated with decreased mitochondrial function and altered nitric oxide signaling in lambs with pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2008 Jan;294(1):L46-56. doi: 10.1152/ajplung.00247.2007. Epub 2007 Nov 16.
- Background: PubMed 19447893Kumar S, Sun X, Sharma S, Aggarwal S, Ravi K, Fineman JR, Black SM. GTP cyclohydrolase I expression is regulated by nitric oxide: role of cyclic AMP. Am J Physiol Lung Cell Mol Physiol. 2009 Aug;297(2):L309-17. doi: 10.1152/ajplung.90538.2008. Epub 2009 May 15.
- Background: PubMed 19818875Sharma S, Kumar S, Sud N, Wiseman DA, Tian J, Rehmani I, Datar S, Oishi P, Fratz S, Venema RC, Fineman JR, Black SM. Alterations in lung arginine metabolism in lambs with pulmonary hypertension associated with increased pulmonary blood flow. Vascul Pharmacol. 2009 Nov-Dec;51(5-6):359-64. doi: 10.1016/j.vph.2009.09.005. Epub 2009 Oct 8.
- Background: PubMed 19825830Tian J, Smith A, Nechtman J, Podolsky R, Aggarwal S, Snead C, Kumar S, Elgaish M, Oishi P, Goerlach A, Fratz S, Hess J, Catravas JD, Verin AD, Fineman JR, She JX, Black SM. Effect of PPARgamma inhibition on pulmonary endothelial cell gene expression: gene profiling in pulmonary hypertension. Physiol Genomics. 2009 Dec 30;40(1):48-60. doi: 10.1152/physiolgenomics.00094.2009. Epub 2009 Oct 13.
- Background: PubMed 22293025Aggarwal S, Gross C, Fineman JR, Black SM. Oxidative stress and the development of endothelial dysfunction in congenital heart disease with increased pulmonary blood flow: lessons from the neonatal lamb. Trends Cardiovasc Med. 2010 Oct;20(7):238-46. doi: 10.1016/j.tcm.2011.11.010.
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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.
Jeffrey Fineman, MD principal investigator
University of California, San Francisco
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 IV L-carnitine in people with Heart Septal Defects, Ventricular and Atrioventricular Septal Defect, run by University of California, San Francisco 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 6 inclusion and 5 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: withdrawn, as of the sponsor's last update on 6 May 2020. 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.
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 was withdrawn before enrolling participants, so there are no results.
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?
Blood carnitine level (free, total, and acylcarnitine) (time frame: At enrollment (first dose), and again 24 and 48 hrs after enrollment. 2 hours after enrollment (at time of second dose) and 0.5, 1.5, 3, 5, 9, 12, and 24h after the second dose.). 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 NCT01825369, which also lists 15 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 6 May 2020.