HypoalbuminemiaNCT00723762
Valproic Acid-associated Hypoalbuminemia in Medically Fragile Patients
An observational study of Hypoalbuminemia, run by Akron Children's Hospital at 1 site in United States.
Trial summary
The purpose of this study is to investigate potential mechanisms of valproic acid-associated low serum albumin in medically fragile pediatric and young adult epileptic patients of a long-term care facility. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hypoalbuminemia
- What is being tested?
- Specimen collection
- Type of treatment
- Surgery or procedure
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2009to Dec 2010
- Phase
- Observational
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Medically fragile residents of the Hattie Larlham Long Term Care Facilit.
Who may be able to join
- Resident of Hattie Larlham long-term care facility receiving VPA for > 3 months at the start of the study
- Resident of Hattie Larlham long-term care facility matched to a resident receiving VPA for > 3 month based on concomitant AED, length of time on AED, age, and gender
- Resident of Hattie Larlham long-term care facility not receiving AED matched to a resident receiving VPA for > 3 month based on age and gender
Who cannot join
- Received albumin products within the past 1 month
- Receiving VPA for < 3 months or discontinuation of VPA therapy within the past four weeks
- Medical need for specific protein supplementation
- Diagnosed with protein-losing nephropathy or enteropathy
Trial locations and contacts
1 site in 1 country.
United States1 site
Hattie Larlham Center for Children with Disabilities
Mantua, Ohio, 44255
About this study
Official title: Valproic Acid-associated Hypoalbuminemia in Medically Fragile Pediatric and Young Adult Patients in a Long Term Care Facility Part 1: Potential Mechanism for Decreased Albumin Synthesis
The purpose of this study is to investigate potential mechanisms of valproic acid-associated low serum albumin in medically fragile pediatric and young adult epileptic patients of a long-term care facility.
Read the detailed description
Valproic acid (VPA) is a long-chain fatty acid frequently used as an antiepileptic agent in pediatric and adult seizure patients. Other adverse effects that have been associated with VPA use include hepatic steatosis, altered mitochondrial function and decreased concentrations of serum proteins. The exact mechanism or mechanisms by which VPA induces these associated adverse drug effects are not fully understood though multiple theories have been postulated including impaired vesicle transport within the hepatocyte, inhibition of hepatic synthetic metabolic pathways and renal protein loss. Decreased serum albumin concentrations with concomitant VPA use have been identified in multiple studies. Albumin synthesis is sensitive to tryptophan concentrations (other amino acids are also able to stimulate albumin synthesis), oncotic pressure near the synthetic site, and energy supply while albumin release from the hepatocyte is sensitive to intrahepatocellular potassium concentrations. Based on available literature, VPA appears to inhibit an enzyme(s) either directly or indirectly involved with albumin synthesis or albumin gene expression. VPA is known to inhibit the urea cycle, including patients with ornithine-transcarbamylase (OTC) deficiency, possibly by inhibiting mitochondrial carbamoyl-phosphate synthase. Oratz et al discussed the potential correlation between the urea cycle and albumin synthesis identified after the administration of various amino acids increased both albumin and urea synthesis. Ornithine is an intermediate amino acid within the urea cycle and it is also a precursor to polyamines which have been shown to increase the degree of aggregation of polysomes, responsible for protein synthesis, bound to the endoplasmic reticulum. Thus, VPA may indirectly inhibit protein synthesis by interfering with the urea cycle leading to decreased ornithine concentrations and subsequently a decrease in polyamine concentrations and a decrease in the number of bound polysomes resulting in alterations in albumin synthesis and release. The purpose of this study is to investigate potential mechanisms of VPA-associated hypoalbuminemia in medically fragile pediatric and young adult epileptic patients of a long-term care facility.
- Conditions
- Hypoalbuminemia
- Being tested
- Specimen collection
- Keywords
- Valproic acid, Urea cycle, Ornithine, Valproate, Side effect
- Medical subject headings
- Hypoalbuminemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Specimen collectionProcedure or surgery
A blood sample and a spot urine sample will be obtained from all eligible patients receiving VPA at the start of the study.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Resident of Hattie Larlham long-term care facility receiving VPA Receives: Procedure: Specimen collection | |
| 2 | Control AED patients will be recruited based on similar AED regimens excluding VPA, length of time on AED (number of months to >1 year), age, and gender; one control patient per VPA patient. | |
| 3 | Control non-AED patients will be recruited based on age and gender; one control patient per VPA patient. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome will be serum albumin concentrations at baseline in the patients receiving VPA.
Measured: Baseline
Secondary outcomes (1)
Secondary outcome variables will include serum amino acid concentrations, total protein, AST, ALT, alkaline phosphatase, ammonia, BUN, and sCr and urine albumin, protein, and urea.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2008 (estimated)
- Study startFeb 2009
- Primary completionDec 2009
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HypoalbuminemiaStudies 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
- Observational
- Observational model
- Case-control
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Akron Children's Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Michael Reed, PharmD, Principal investigator, Akron Children's Hospital Research CenterMartha Blackford, PharmD, Study chair, Akron Children's HospitalRichard Grossberg, MD, Study chair, Hattie Larlham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00723762
- Sponsor's protocol ID
- Valproic Acid-Albumin
- Status last verified
- Mar 2011
- First submitted
- 25 Jul 2008
- Last updated
- 10 Mar 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Attilakos A, Voudris KA, Katsarou E, Prassouli A, Mastroyianni S, Garoufi A. Transient decrease in serum albumin concentrations in epileptic children treated with sodium valproate monotherapy. Clin Neuropharmacol. 2007 May-Jun;30(3):145-9. doi: 10.1097/wnf.0b013e3180318a99.
PubMed 17545749Hauser E, Seidl R, Freilinger M, Male C, Herkner K. Hematologic manifestations and impaired liver synthetic function during valproate monotherapy. Brain Dev. 1996 Mar-Apr;18(2):105-9. doi: 10.1016/0387-7604(95)00139-5.
PubMed 8733899Rugino TA, Janvier YM, Baunach JM, Bilat CA. Hypoalbuminemia with valproic acid administration. Pediatr Neurol. 2003 Nov;29(5):440-4. doi: 10.1016/s0887-8994(03)00310-2.
PubMed 14684241Oratz M, Rothschild MA, Schreiber SS, Burks A, Mongelli J, Matarese B. The role of the urea cycle and polyamines in albumin synthesis. Hepatology. 1983 Jul-Aug;3(4):567-71. doi: 10.1002/hep.1840030415.
PubMed 6407956Karikas GA, Schulpis KH, Bartzeliotou A, Karakonstantakis T, Georgala S, Kanavaki I, Demetriou E, Papassotiriou I. Lipids, lipoproteins, apolipoproteins, selected trace elements and minerals in the serum of children on valproic acid monotherapy. Basic Clin Pharmacol Toxicol. 2006 Jun;98(6):599-603. doi: 10.1111/j.1742-7843.2006.pto_402.x.
PubMed 16700824Castro-Gago M, Rodrigo-Saez E, Novo-Rodriguez I, Camina MF, Rodriguez-Segade S. Hyperaminoacidemia in epileptic children treated with valproic acid. Childs Nerv Syst. 1990 Dec;6(8):434-6. doi: 10.1007/BF00302087.
PubMed 2095300
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Valproic Acid-associated Hypoalbuminemia in Medically Fragile Pediatric and Young Adult Patients in a Long Term Care Facility Part 1: Potential Mechanism for Decreased Albumin Synthesis
- ClinicalTrials.gov ID
- NCT00723762
- Acronym / sponsor ID
- Valproic Acid-Albumin
- Conditions
- Hypoalbuminemia
- Keywords
- Valproic acid, Urea cycle, Ornithine, Valproate, Side effect
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Akron Children's HospitalUniversity, hospital or other
- Study start
- Feb 2009
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 29 Jul 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 investigate potential mechanisms of valproic acid-associated low serum albumin in medically fragile pediatric and young adult epileptic patients of a long-term care facility.
Detailed description
Valproic acid (VPA) is a long-chain fatty acid frequently used as an antiepileptic agent in pediatric and adult seizure patients. Other adverse effects that have been associated with VPA use include hepatic steatosis, altered mitochondrial function and decreased concentrations of serum proteins. The exact mechanism or mechanisms by which VPA induces these associated adverse drug effects are not fully understood though multiple theories have been postulated including impaired vesicle transport within the hepatocyte, inhibition of hepatic synthetic metabolic pathways and renal protein loss. Decreased serum albumin concentrations with concomitant VPA use have been identified in multiple studies. Albumin synthesis is sensitive to tryptophan concentrations (other amino acids are also able to stimulate albumin synthesis), oncotic pressure near the synthetic site, and energy supply while albumin release from the hepatocyte is sensitive to intrahepatocellular potassium concentrations. Based on available literature, VPA appears to inhibit an enzyme(s) either directly or indirectly involved with albumin synthesis or albumin gene expression. VPA is known to inhibit the urea cycle, including patients with ornithine-transcarbamylase (OTC) deficiency, possibly by inhibiting mitochondrial carbamoyl-phosphate synthase. Oratz et al discussed the potential correlation between the urea cycle and albumin synthesis identified after the administration of various amino acids increased both albumin and urea synthesis. Ornithine is an intermediate amino acid within the urea cycle and it is also a precursor to polyamines which have been shown to increase the degree of aggregation of polysomes, responsible for protein synthesis, bound to the endoplasmic reticulum. Thus, VPA may indirectly inhibit protein synthesis by interfering with the urea cycle leading to decreased ornithine concentrations and subsequently a decrease in polyamine concentrations and a decrease in the number of bound polysomes resulting in alterations in albumin synthesis and release. The purpose of this study is to investigate potential mechanisms of VPA-associated hypoalbuminemia in medically fragile pediatric and young adult epileptic patients of a long-term care facility.
Study design
- Observational model
- Case-control
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | – | Procedure: Specimen collectionResident of Hattie Larlham long-term care facility receiving VPA |
| 2 | – | –Control AED patients will be recruited based on similar AED regimens excluding VPA, length of time on AED (number of months to >1 year), age, and gender; one control patient per VPA patient. |
| 3 | – | –Control non-AED patients will be recruited based on age and gender; one control patient per VPA patient. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Medically fragile residents of the Hattie Larlham Long Term Care Facilit.
Key inclusion criteria (3 listed)
- Resident of Hattie Larlham long-term care facility receiving VPA for > 3 months at the start of the study
- Resident of Hattie Larlham long-term care facility matched to a resident receiving VPA for > 3 month based on concomitant AED, length of time on AED, age, and gender
- Resident of Hattie Larlham long-term care facility not receiving AED matched to a resident receiving VPA for > 3 month based on age and gender
Key exclusion criteria (4 listed)
- Received albumin products within the past 1 month
- Receiving VPA for < 3 months or discontinuation of VPA therapy within the past four weeks
- Medical need for specific protein supplementation
- Diagnosed with protein-losing nephropathy or enteropathy
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 |
|---|---|---|
| Specimen collectionA blood sample and a spot urine sample will be obtained from all eligible patients receiving VPA at the start of the study. | Procedure or surgery | 1 |
Primary outcome
The primary outcome will be serum albumin concentrations at baseline in the patients receiving VPA.
Time frame: Baseline
1 secondary outcome
Secondary outcome variables will include serum amino acid concentrations, total protein, AST, ALT, alkaline phosphatase, ammonia, BUN, and sCr and urine albumin, protein, and urea.
Time frame: Baseline
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 10 Mar 2011.
- Background: PubMed 17545749Attilakos A, Voudris KA, Katsarou E, Prassouli A, Mastroyianni S, Garoufi A. Transient decrease in serum albumin concentrations in epileptic children treated with sodium valproate monotherapy. Clin Neuropharmacol. 2007 May-Jun;30(3):145-9. doi: 10.1097/wnf.0b013e3180318a99.
- Background: PubMed 8733899Hauser E, Seidl R, Freilinger M, Male C, Herkner K. Hematologic manifestations and impaired liver synthetic function during valproate monotherapy. Brain Dev. 1996 Mar-Apr;18(2):105-9. doi: 10.1016/0387-7604(95)00139-5.
- Background: PubMed 14684241Rugino TA, Janvier YM, Baunach JM, Bilat CA. Hypoalbuminemia with valproic acid administration. Pediatr Neurol. 2003 Nov;29(5):440-4. doi: 10.1016/s0887-8994(03)00310-2.
- Background: PubMed 6407956Oratz M, Rothschild MA, Schreiber SS, Burks A, Mongelli J, Matarese B. The role of the urea cycle and polyamines in albumin synthesis. Hepatology. 1983 Jul-Aug;3(4):567-71. doi: 10.1002/hep.1840030415.
- Background: PubMed 16700824Karikas GA, Schulpis KH, Bartzeliotou A, Karakonstantakis T, Georgala S, Kanavaki I, Demetriou E, Papassotiriou I. Lipids, lipoproteins, apolipoproteins, selected trace elements and minerals in the serum of children on valproic acid monotherapy. Basic Clin Pharmacol Toxicol. 2006 Jun;98(6):599-603. doi: 10.1111/j.1742-7843.2006.pto_402.x.
- Background: PubMed 2095300Castro-Gago M, Rodrigo-Saez E, Novo-Rodriguez I, Camina MF, Rodriguez-Segade S. Hyperaminoacidemia in epileptic children treated with valproic acid. Childs Nerv Syst. 1990 Dec;6(8):434-6. doi: 10.1007/BF00302087.
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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.
Michael Reed, PharmD principal investigator
Akron Children's Hospital Research Center
Martha Blackford, PharmD study chair
Akron Children's Hospital
Richard Grossberg, MD study chair
Hattie Larlham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypoalbuminemia, run by Akron Children's Hospital 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 3 inclusion and 4 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 10 Mar 2011. 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?
The primary outcome will be serum albumin concentrations at baseline in the patients receiving VPA. (time frame: Baseline). 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 NCT00723762, which also lists 6 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 10 Mar 2011.